Clinical Topic A-Z Clinical Speciality

Asthma

Asthma
D001249Asthma
AllergiesChild healthRespiratory
2011-06-01Last revised in June 2011

Asthma - Summary

Asthma is a chronic inflammatory condition of the airways.

The airways are hyper-responsive and constrict easily in response to a wide range of stimuli. This may result in coughing, wheezing, chest tightness, and shortness of breath.

Narrowing of the airways is usually reversible (either spontaneously or with medication), leading to intermittent symptoms, but in some people with chronic asthma, the inflammation may lead to irreversible airflow obstruction.

Asthma is a common condition. A report by Asthma UK states that 5.2 million people in the UK have asthma.

The probability of someone having asthma is increased if they have:

Wheeze, breathlessness, chest tightness, and cough, particularly if symptoms are worse at night and in the early morning; occur in response to exercise, allergen exposure, and cold air; occur after taking aspirin or beta-blockers; occur even when the person has not got a cold.

History of atopic disorder.

Family history of asthma and/or atopic disorder.

Widespread wheeze (bilateral, predominantly expiratory).

Prolonged expiration.

Increased respiratory rate.

Spirometry should be performed on all adults to assess for the presence, severity, and reversibility of airway obstruction. Spirometry is recommended for children where the diagnosis of asthma is uncertain — if they are able to perform the test (usually older than 5 years).

For people with an intermediate or high probability of asthma, a trial of treatment to confirm the diagnosis should be considered. For people with a low probability of asthma, an alternative diagnosis should be considered.

A stepped approach to the management of chronic asthma is recommended. For people over the age of 5 years of age:

Step 1: occasional relief bronchodilator — an inhaled short-acting beta2 agonist as required.

Step 2: regular inhaled preventer therapy — an inhaled corticosteroid or, if an inhaled corticosteroid is not tolerated, a leukotriene receptor antagonist or cromone.

Step 3: inhaled corticosteroid and long-acting inhaled beta2 agonist. If symptom control is inadequate with a long-acting inhaled beta2 agonist, consider an alternative add-on treatment, such as a leukotriene receptor antagonist or modified-release theophylline before moving to step 4.

Step 4: high-dose inhaled corticosteroid and regular bronchodilator.

Step 5: regular corticosteroid tablets and referral to a specialist in respiratory medicine.

For children under 5 years, a stepped approach is also recommended.

Step 1: occasional relief bronchodilator — an inhaled short-acting beta2 agonist as required.

Step 2: regular preventer therapy — an inhaled corticosteroid or, if an inhaled corticosteroid is not tolerated, a leukotriene receptor antagonist (children 2–5 years).

Step 3: if younger than 2 years, referral to a respiratory paediatrician. For children aged 2–5 years, add a leukotriene receptor antagonist.

Step 4: referral to a respiratory paediatrician.

Acute exacerbations of asthma are generally managed with a short course of oral prednisolone and a short-acting beta2-agonist. Hospital admission is necessary for people with life threatening asthma or severe asthma that does not adequately respond to initial treatment.

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This CKS topic covers the primary care management of acute and chronic asthma in adults and children.

This CKS topic is based on the 2011 British guideline on the management of asthma: a national clinical guideline from the Scottish Intercollegiate Guidelines Network and British Thoracic Society [SIGN and BTS, 2011].

There are separate CKS topics on Chest infections - adult, Chronic obstructive pulmonary disease, and Smoking cessation.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

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Changes

Last revised in June 2011

December 2013 — minor update. A broken link to the Children's Asthma Control Test has been fixed.

July 2013 — minor update. Links to the DVLA website have been updated.

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic [BMA and NHS Employers, 2013].

May 2013 — minor update. Minor change to the text to improve the clarity of how to manage people who are awaiting hospital admission.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic [BMA and NHS Employers, 2012]. Issued in April 2012.

February 2012 — minor update. A recommendation to advise people inhaling terbutaline via a turbohaler to rinse their mouth after each use to minimize systemic adverse effects has been added, following an update to the manufacturer's Summary of Product Characteristics [ABPI Medicines Compendium, 2011b]. Issued in March 2012.

November 2011 — minor update. The black triangle has been removed from Serevent Evohaler® (salmeterol cfc-free inhaler); prescriptions have been amended to reflect this. Issued in December 2011.

June 2011 — annual updates from the British guideline on the management of asthma: a national clinical guideline by SIGN/BTS are now included [SIGN and BTS, 2011]. Issued in June 2011.

May 2011 — minor update. The 2011/2012 QOF indicators and the 2010/2011 QIPP options for local implementation have been added to this topic [BMA and NHS Employers, 2011; NPC, 2011]. Issued in June 2011.

April 2011 — minor update. Pulmicort pMDI inhalers have been removed from this topic as they have been discontinued. Issued in June 2011.

March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

February 2011 — minor update. The range of dry powder inhaler devices included as prescriptions has been updated. Issued in February 2011.

December 2010 — minor update. The Flixotide Diskhaler® (fluticasone) range has been discontinued. The prescription has been removed. Issued in December 2010.

October 2010 — minor update. Information on fitness to drive from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive has been added [DVLA, 2010]. Issued in November 2010.

September 2010 — minor update. The Medicines and Healthcare products Regulatory Agency has issues a reminder to prescribers that, for most children, a daily dose of 24 micrograms formoterol is sufficient [MHRA, 2010]. Issued in September 2010.

March 2010 — minor update. All strengths of Beclazone® inhalers have been discontinued. Prescriptions removed. For advice regarding switching from CFC beclometasone to CFC-free beclometasone, see the section What dose of inhaled corticosteroid should I prescribe?. Issued in March 2010.

January 2010 – minor update. Ciclesonide (Alvesco®) is no longer a black triangle product. Minor addition to text regarding drug interactions with theophylline. Issued in January 2010.

December 2009 — minor update. Clenil Modulite® (beclometasone CFC-free) is no longer a black triangle product. Prescription updated. Issued in December 2009.

November 2009 — minor update. The Supporting evidence section on Symbicort Smart® has been reworded to make it clear that the data summarized are from a single Cochrane review. Issued in November 2009.

August 2009 — minor update. The annual updates from the British guideline on the management of asthma: a national clinical guideline by SIGN/BTS are now included [SIGN and BTS, 2008b]. Issued in August 2009.

May 2009 — updated to include information and prescriptions for budesonide CFC-free pMDI. The Nebuhaler® spacer device has been discontinued. The prescription has been replaced with the NebuChamber® spacer device. Issued in June 2009.

April 2009 — minor update. The Quality and Outcomes Framework (QOF) indicators for stopping smoking that relate to asthma have been added to the Goals and outcome measures section. Issued in May 2009.

February 2009 — minor update. Flixotide® 50 microgram diskhaler and all strengths of the Aerobec® breath-actuated inhaler have been discontinued. Prescriptions removed. Issued March 2009.

August 2008 — update to the diagnosis and assessment sections following the publication of the British guideline on the management of asthma: a national clinical guideline by SIGN/BTS [SIGN and BTS, 2008a]. Issued in November 2008.

March 2008 — minor update to include advice from the Medicines and Healthcare products Regulatory Agency (MHRA) regarding the use of short-acting beta2-agonists in people who have a history of heart disease. Issued in March 2008.

September to December 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

This CKS topic includes revisions in the 2007 update to the SIGN/BTS British Guideline on the Management of Asthma.

Previous changes

June 2007 — updated. Nebuhaler® discontinued. Prescriptions replaced with Nebuhaler® + mask, which continues to be available. Issued in June 2007.

May 2007 — updated. Becotide® and Becloforte® discontinued. Prescriptions removed. Issued in May 2007.

March 2007 — updated. Prescriptions and dosing information for Clenil Modulite® (CFC-free beclometasone) and CFC-free formoterol included. Information on spacer device compatibilities also updated. Issued in March 2007.

July–September 2006 — updated. Validated in December 2006 and issued in January 2007.

This guidance is based on the Scottish Intercollegiate Guidelines Network and British Thoracic Society guidelines on the management of asthma [SIGN and BTS, 2005]. As the SIGN and BTS guideline was not updated in 2006, there are no major changes to recommendations. The guidance has been restructured with the addition of an overview section, and recent safety information on drugs has been added. Some minor technical and evidence information has not been updated due to time restraints; these will be addressed in the next update (due to commence in July 2007).

July 2006 — minor update. All strengths of Ventodisks® (salbutamol dry powder Diskhaler®) will be discontinued from the end of September 2006 and prescriptions have been removed. Issued in July 2006.

April 2006 — minor update. Prescriptions for CFC-free nedocromil and salmeterol pressurized metered dose inhalers have replaced those for CFC-containing inhalers. Information on changing to CFC-free inhalers included in Medicines Management. Issued in May 2006.

January 2006 — minor update. Volumatic® spacer device re-introduced and prescriptions included; terbutaline pressurized metered dose inhalers have been discontinued and prescriptions removed. Issued in February 2006.

August 2005 — updated to include revisions in the 2005 update to the SIGN/BTS British Guideline on the Management of Asthma, and the new CMO recommendations on the pneumococcal immunization programme. Volumatic® spacer device discontinued and prescriptions removed; advice for using alternative spacer devices included. Validated in September 2005 and issued in November 2005.

August 2004 — updated to include revisions in the 2004 update to the SIGN/BTS British Guideline on the Management of Asthma. Validated in September 2004 and issued in November 2004.

April 2003 — reviewed. Validated in September 2003 and issued in October 2003. This guidance supersedes the CKS guidance Asthma — age under 5 years, which has been withdrawn.

April 2002 — reviewed and updated to incorporate Inhaler devices for routine treatment of chronic asthma in older children (aged 5–15 years), technology appraisal guidance no. 38, issued by the National Institute for Health and Care Excellence (April 2002).

April 1999 — reviewed. Validated in July 1999 and issued in August 1999.

June 1998 — written.

Update

New evidence

Evidence-based guidelines

Guidelines published since the last revision of this topic:

Bateman, E.D., Hurd, S.S., Barnes, P.J., et al. (2008) Global strategy for asthma management and prevention: GINA executive summary. European Respiratory Journal 31(1), 143-178. [Abstract] [Free Full-text]

Dombrowski, M.P., Schatz, M., and ACOG Committee on Practice Bulletins-Obstetrics (2008) ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 90, February 2008: asthma in pregnancy. Obstetrics and Gynecology 111(2 Pt 1), 457-464. [Abstract]

ICSI (2010) Diagnosis and treatment of asthma. Institute for Clinical Systems Improvement www.icsi.org [Free Full-text]

National Heart, Lung, and Blood Institute and National Asthma Education and Prevention Program (2007) Expert panel report 3: guidelines for the diagnosis and management of asthma. National Institutes of Health. www.nhlbi.nih.gov [Free Full-text]

VA/DoD Management of Asthma Working Group (2009) Management of asthma in children and adults. Department of Veterans Affairs and Department of Defense (US). www.healthquality.va.gov [Free Full-text]

Consensus statements published since the last revision of this topic:

Bacharier, L.B., Boner, A., Carlsen, K.H., et al. (2008) Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy 63(1), 5-34. [Abstract] [Free Full-text]

Tarlo, S.M., Balmes, J., Balkissoon, R., et al. (2008) Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus statement. Chest 134(3 Suppl), 1S-41S. [Abstract] [Free Full-text]

NICE has produced an evidence summary on new medicines for asthma:

NICE (2013) ESNM22: Asthma: beclometasone/formoterol (Fostair) for maintenance and reliever treatment. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2014) ESNM35: Asthma: fluticasone furoate/vilanterol (Relvar Ellipta) combination inhaler. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

HTAs (Health Technology Assessments)

NICE health technology appraisals published since the last revision of this topic.

NICE (2007) Inhaled corticosteroids for the treatment of chronic asthma in children under the age of 12 years. NICE technology appraisal guidance 131. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2008) Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. NICE technology appraisal guidance 138. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2010) Omalizumab for the treatment of severe persistent allergic asthma in children aged 6 to 11 years. NICE technology appraisal guidance 201. National Institute for Health and Care Excellence. www.nice.org.uk [Free full-text]

Health technology assessments published since the last revision of this topic.

CADTH (2009) Long-acting beta2-agonist and inhaled corticosteroid combination therapy for adult persistent asthma: systematic review of clinical outcomes and economic evaluation. Technology report number 122. Canadian Agency for Drugs and Technologies in Health. www.cadth.ca [Free Full-text]

Main, C., Shepherd, J., Anderson, R., et al. (2008) Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2agonists for the treatment of chronic asthma in children under the age of 12 years. Health Technology Assessment 12(20), 1-174. [Abstract] [Free Full-text]

Economic appraisals

Economic appraisals published since the last revision of this topic:

Norman, G., Faria, R., Paton, F., et al. (2013) Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technology Assessment 17(52), 1-342. [Abstract] [Free Full-text]

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Abramson, M.J., Puy, R.M., and Weiner, J.M. (2010) Injection allergen immunotherapy for asthma (Cochrane Review). The Cochrane Library. Issue 8. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Adams, N., Lasserson, T.J., Cates, C.J., and Jones, P.W. (2007) Fluticasone versus beclomethasone or budesonide for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Adams, N.P., Bestall, J.C., Jones, P., et al. (2008) Fluticasone at different doses for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Adams, N.P., Bestall, J.C., Lasserson, T.J., et al. (2008) Fluticasone versus placebo for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Adeniyi, F.B. and Young, T. (2012) Weight loss interventions for chronic asthma (Cochrane Review). The Cochrane Library. Issue 7. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Allen, S., Britton, J., Leonardi-Bee, J. (2009) Association between antioxidant vitamins and asthma outcomes: systematic review and meta-analysis. Thorax 64(7), 610-619. [Abstract]

Arnold, E., Clark, C.E., Lasserson, T.J., and Wu, T. (2008) Herbal interventions for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Bahadori, K., Doyle-Waters, M.M., Marra, C., et al. (2009) Economic burden of asthma: a systematic review. BMC Pulmonary Medicine 9(1), 24. [Abstract] [Free Full-text]

Bailey, E.J., Kruske, S.G., Morris, P.S., et al. (2008) Culture-specific programs for children and adults from minority groups who have asthma (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Bateman, E., Nelson, H., Bousquet, J., et al. (2008) Meta-analysis: effects of adding salmeterol to inhaled corticosteroids on serious asthma-related events. Annals of Internal Medicine 149(1), 33-42. [Abstract] [Free Full-text]

Beggs, S., Foong, Y.C., Le, H.C.T., et al. (2013) Swimming training for asthma in children and adolescents aged 18 years and under (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Blake, K. and Lima, J. (2011) Asthma in sickle cell disease: implications for treatment. Anemia 2011, 740235. [Abstract] [Free Full-text]

Bonini, M., Di Mambro, C., Calderon, M.A., et al. (2013) Beta2-agonists for exercise-induced asthma (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Boyd, M., Lasserson, T.J., McKean, M.C., et al. (2009) Interventions for educating children who are at risk of asthma-related emergency department attendance (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Bravata, D.M., Gienger, A.L., Holty, J.E., et al. (2009) Quality improvement strategies for children with asthma: a systematic review. Archives of Pediatrics and Adolescent Medicine 163(6), 572-581. [Abstract] [Free Full-text]

Brozek, J.L., Kraft, M., Krishnan, J.A., et al. (2012) Long-acting beta2-agonist step-off in patients with controlled asthma: systematic review with meta-analysis. Archives of Internal Medicine 172(18), 1365-1375. [Abstract]

Bruurs, M.L., van der Giessen, L.J., and Moed, H. (2013) The effectiveness of physiotherapy in patients with asthma: a systematic review of the literature. Respiratory Medicine 107(4), 483-494. [Abstract]

Castro-Rodriguez, J.A. and Rodrigo, G.J. (2009) Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics 123(3), e519-e525. [Abstract] [Free Full-text]

Castro-Rodriguez, J.A. and Rodrigo, G.J. (2009) The role of inhaled corticosteroids and montelukast in children with mild-moderate asthma: results of a systematic review with meta-analysis. Archives of Disease in Childhood 95(5), 365-370. [Abstract]

Castro-Rodriguez, J.A. and Rodrigo, G.J. (2012) A systematic review of long-acting beta2-agonists versus higher doses of inhaled corticosteroids in asthma. Pediatrics 130(3), e650-e657. [Abstract]

Cates, C.J. and Cates, M.J. (2008) Regular treatment with salmeterol for chronic asthma: serious adverse events (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J., and Lasserson, T.J. (2010) Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J., Lasserson, T.J., and Jaeschke, R. (2009) Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J., Lasserson, T.J. and Jaeschke, R. (2009) Regular treatment with salmeterol and inhaled steroids for chronic asthma: serious adverse effects (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J. and Lasserson, T.J. (2009) Combination formoterol and inhaled steroid versus beta2-agonist as relief medication for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J. and Lasserson, T.J. (2009) Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J. and Lasserson, T.J. (2009) Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Chauhan, B.F., Chartrand, C., and Ducharme, F.M. (2012) Intermittent versus daily inhaled corticosteroids for persistent asthma in children and adults (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Chauhan, B.F., Ben Salah, R. And Ducharme, F.M. (2013) Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

de Aguiar, M.M., da Silva, H.J., Rizzo, J.A., et al. (2013) Inhaled beclomethasone in pregnant asthmatic women - a systematic review. Allergologia et immunopathologia epub ahead of print. [Abstract]

Ducharme, F.M., Lasserson, T.J., and Cates, C.J. (2011) Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma (Cochrane Review). The Cochrane Library. Issue 5. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Eijkemans, M., Mommers, M., Draaisma, J.M., et al. (2012) Physical activity and asthma: a systematic review and meta-analysis. PLoS One 7(12), e50775. [Abstract] [Free Full-text]

El-Zein, M., Parent, M.E., Benedetti, A., and Rousseau, M.C. (2009) Does BCG vaccination protect against the development of childhood asthma? A systematic review and meta-analysis of epidemiological studies. International Journal of Epidemiology 39(2), 469-486. [Abstract] [Free Full-text]

Eneli, I.U., Skybo, T., and Camargo, C.A. (2008) Weight loss and asthma: a systematic review. Thorax 63(8), 671-676. [Abstract]

Ernst, E. (2009) Spinal manipulation for asthma: a systematic review of randomised clinical trials. Respiratory Medicine 103(12), 1791-1795. [Abstract]

Etminan, M., Sadatsafavi, M., Jafari, S., et al. (2009) Acetaminophen use and the risk of asthma in children and adults: a systematic review and metaanalysis. Chest 136(5), 1316-1323. [Abstract] [Free Full-text]

Everhart, R.S. and Fiese, B.H. (2008) Asthma severity and child quality of life in pediatric asthma: a systematic review. Patient Education and Counseling 75(2), 162-168. [Abstract]

Frois, C., Wu, E.Q., Ray, S., and Colice, G.L. (2009) Inhaled corticosteroids or long-acting beta-agonists alone or in fixed-dose combinations in asthma treatment: a systematic review of fluticasone/budesonide and formoterol/salmeterol. Clinical Therapeutics 31(12), 2779-2803. [Abstract]

Gao, J., Gao, X., Li, W., et al. (2008) Observational studies on the effect of dietary antioxidants on asthma: a meta-analysis. Respirology 13(4), 528-536. [Abstract]

Garcia-Marcos, L., Castro-Rodriguez, J.A., Weinmayr, G., et al. (2013) Influence of Mediterranean diet on asthma in children: a systematic review and meta-analysis. Pediatric Allergy and Immunology 24(4), 330-338. [Abstract]

George, M. and Topaz, M. (2013) A systematic review of complementary and alternative medicine for asthma self-management. Nursing Clinics of North America 48(1), 53-149. [Abstract]

Gotzche, P.C. and Johansen, H.K. (2008) House dust mite control measures for asthma (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Hagan, J.B., Samant, S.A., Volcheck, G.W., et al. (2014) The risk of asthma exacerbation after reducing inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. Allergy 69(4), 510-516. [Abstract]

Hart, K., Weatherall, M., Shirtcliffe, P., and Beasley, R. (2009) Frequency of dosing and comparative doses of mometasone furoate: a meta-analysis. Respirology 14(8), 1166-1172 [Abstract]

Jaeschke, R., O'Byrne, P.M., Mejza, F., et al. (2008) The safety of long acting beta agonists among patients with asthma using inhaled corticosteroids. American Journal of Respiratory and Critical Care Medicine 178(10), 1009-1016. [Abstract] [Free Full-text]

Jartti, T. (2008) Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for pediatric asthma? European Journal of Pediatrics 167(7), 731-736. [Abstract]

Jat, K.R. and Chawla, D. (2012) Ketamine for management of acute exacerbations of asthma in children (Cochrane review). The Cochrane Library. Issue 11. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Jat, K.R. and Khairwa, A. (2013) Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulmonary Pharmacology and Therapeutics 26(2), 239-48. [Abstract]

Jia, C.E., Zhang, H.P., Lv, Y., et al. (2013) The Asthma Control Test and Asthma Control Questionnaire for assessing asthma control: systematic review and meta-analysis. Journal of Allergy and Clinical Immunology 131(3), 695-703. [Abstract]

Joos, S., Miksch, A., Szecsenyi, J., et al. (2008) Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax 63(5), 453-462. [Abstract]

Juel, C.T., Ali, Z., Nilas, L., and Ulrik, C.S. (2012) Asthma and obesity: does weight loss improve asthma control? A systematic review. Journal of Asthma and Allergy 2012(5), 21-26. [Abstract] [Free Full-text]

Kramer, S., Rottier, B.L., Scholten, R.J.P.M. and Boluyt, N. (2013) Ciclesonide versus other inhaled corticosteroids for chronic asthma in children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Lasserson, T.J., Cates, C.J., Ferrara, G., and Casali, L. (2008) Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Lim, R.H., Kobzik, L., and Dahl, M. (2010) Risk of asthma in offspring of asthmatic mothers versus fathers: a meta-analysis. PLoS One 5(4), e10134. [Abstract] [Free Full-text]

Lim, A., Stewart, K., Konig, K. and George, J. (2011) Systematic review of the safety of regular preventive asthma medications during pregnancy. Annals of Pharmacotherapy 45(7-8), 931-945. [Abstract]

Maas, T., Kaper, J., Sheikh, A., et al. (2009) Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Manning, P., Gibson, P.G., and Lasserson, T.J. (2008) Ciclesonide versus other inhaled steroids for chronic asthma in children and adults (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Manning, P., Gibson, P.G., and Lasserson, T.J. (2008) Ciclesonide versus placebo for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Massingham, K., Fox, S., and Smaldone, A. (2014) Asthma therapy in pediatric patients: a systematic review of treatment with montelukast versus inhaled corticosteroids. Journal of Pediatric Health Care 28(1), 51-62. [Abstract]

McLean, S., Chandler, D., Nurmatov, U., et al. (2010) Telehealthcare for asthma (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Milan, S.J., Hart, A., and Wilkinson, M. (2013) Vitamin C for asthma and exercise-induced bronchoconstriction (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Morales, D.R., Jackson, C., Lipworth, B.J., et al. (2013) Adverse respiratory effect of acute beta-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials. Chest epub ahead of print. [Abstract]

Nathani, N., Little, M.A., Kunst, H., et al. (2008) Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective. Thorax 63(10), 883-888 [Abstract]

Ni Chroinin, M., Greenstone, I., Lasserson, T.J., and Ducharme, F.M. (2009) Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Ni Chroinin, M., Lasserson, T.J., Greenstone, I., and Ducharme, F.M. (2009) Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Norman, G., Faria, R., Paton, F., et al. (2013) Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technology Assessment 17(52), 1-342. [Abstract] [Free Full-text]

Nurmatov, U., Devereux, G. and Sheikh, A. (2010) Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis. Journal of Allergy and Clinical Immunology 127(3), 724-733. [Abstract]

Pacheco, D.R., Silva, M.J., Alexandrino, A.M., and Torres, R.M. (2012) Exercise-related quality of life in subjects with asthma: a systematic review. Journal of Asthma 49(5), 487-495. [Abstract]

Petsky, H.L., Cates, C.J., Li, A.M., et al. (2009) Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Postma, J., Karr, C., and Kieckhefer, G. (2009) Community health workers and environmental interventions for children with asthma: a systematic review. Journal of Asthma 46(6), 564-576. [Abstract]

Quon, B.S., FitzGerald, J.M., Lemiere, C., et al. (2010)Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Rank, M.A., Hagan, J.B., Park, M.A., et al. (2013) The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. Journal of Allergy and Clinical Immunology 131(3), 724-729. [Abstract]

Rodriguez, C., Sossa, M., and Lozano, J.M. (2008) Commercial versus home-made spacers in delivering bronchodilator therapy for acute therapy in children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Rodrigo, G.J. and Castro-Rodriquez, J.A. (2013) Daily vs. intermittent inhaled corticosteroids for recurrent wheezing and mild persistent asthma: a systematic review with meta-analysis. Respiratory Medicine 107(8), 1133-1140. [Abstract]

Seale, J.P., Jenkins, C., Wood-Baker, R., and Neville, A.M. (2008) Benefits of fixed-dose combination therapy with inhaled corticosteroids and long-acting bronchodilators as initial maintenance therapy in the management of asthma. Respirology 14(2), 224-229. [Abstract]

Shen, F.Y., Lee, M.S. and Jung, S.K. (2010) Effectiveness of pharmacopuncture for asthma: a systematic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine 2011; 678176. [Abstract] [Free Full-text]

Si, X.B., Zhang, S., Huo, L.Y., et al. (2013) Statin therapy does not improve lung function in asthma: a meta-analysis of randomized controlled trials. Journal of International Medical Research 41(2), 276-283. [Abstract]

Silva, D., Couto, M., Delgado, L., and Moreira, A. (2012) A systematic review of statin efficacy in asthma. Journal of Asthma 49(9), 885-894. [Abstract]

Sindi, A., Todd, D.C., and Nair, P. (2009) Antiinflammatory effects of long-acting beta2-agonists in patients with asthma: a systematic review and meta-analysis. Chest 136(1), 145-154. [Abstract] [Free Full-text]

Takkouche, B., Gonzalez-Barcala, F.J., Etminan, M., and Fitzgerald, M. (2008) Exposure to furry pets and the risk of asthma and allergic rhinitis: a meta-analysis. Allergy 63(7), 857-864. [Abstract] [Free Full-text]

Teoh, L., Cates, C.J., Hurwitz, M., et al. (2012) Anticholinergic therapy for acute asthma in children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Vandenplas, O., Dressel, H., Wilken, D., et al. (2011) Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence. European Respiratory Journal 38(4), 804-811. [Abstract]

van den Oord, R.A.H.M., Sheikh, A. (2009) Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis. BMJ 339, b2433. [Abstract] [Free Full-text]

van der Wouden, J.C., Uijen, J.H.J.M., Bernsen, R.M.D., et al. (2008) Inhaled sodium cromoglycate for asthma in children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Vliagoftis, H., Kouranos, V.D., Betsi, G.I., et al. (2008) Probiotics for the treatment of allergic rhinitis and asthma: systematic review of randomized controlled trials. Annals of Allergy Asthma and Immunology 101(6), 570-579. [Abstract]

Wang, Q., Yu, C., and Sun, Y. (2013) The association between asthma and Helicobacter pylori: a meta-analysis. Helicobacter 18(1), 41-53. [Abstract]

Wanrooij, V.H., Willeboordse, M., Dompeling, E., and Kant, K.D. (2013) Exercise training in children with asthma: a systematic review. British Journal of Sports Medicine epub ahead of print. [Abstract]

Watts, K., and Chavasse, R.J.P.G. (2012) Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 5. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Weatherall, M., Clay, J., James, K., et al. (2009) Dose-response relationship of inhaled corticosteroids and cataracts: a systematic review and meta-analysis. Respirology 14(7), 983-990. [Abstract]

Welsh, E.J., Hasan, M., and Li, P. (2011) Home-based educational interventions for children with asthma (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Welsh, E.J., and Cates, C.J. (2010) Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma (Cochrane Review). The Cochrane Library. Issue 9. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Wijesinghe, M., Weatherall, M., Perrin, K., et al (2009) Risk of mortality associated with formoterol: a systematic review and meta-analysis. European Respiratory Journal 34(4), 803-811. [Abstract] [Free Full-text]

Zairina, E., Stewart, K., Abramson, M.J and George, J. (2014) The effectiveness of non-pharmacological healthcare interventions for asthma management during pregnancy: a systematic review. BMC Pulmonary Medicine 14(1), 46. [Abstract] [Free Full-text]

Zhang, J., Li, X., Xu, J., and Ernst, E. (2012) Laser acupuncture for the treatment of asthma in children: a systematic review of randomized controlled trials. Journal of Asthma 49(7), 773-777. [Abstract]

Zhang, L., Axelsson, I., Chung, M. and Lau, J. (2011) Dose response of inhaled corticosteroids in children with persistent asthma: a systematic review. Pediatrics 127(1), 129-138. [Abstract] [Free Full-text]

Zheng, X., Guan, W., Zheng, J., et al. (2012) Smoking influences response to inhaled corticosteroids in patients with asthma: a meta-analysis. Current Medicine Research and Opinion 28(11), 1791-1798. [Abstract]

Zhou, Y., Yang, M., and Rong Dong, B. (2012) Monosodium glutamate avoidance for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 6. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Primary evidence

Randomized controlled trials published since the last revision of this topic:

Abramson, M.J., Schattner, R.L., Sulaiman, N.D., et al. (2010) Do spirometry and regular follow-up improve health outcomes in general practice patients with asthma or COPD? A cluster randomised controlled trial. Medical Journal of Australia 193(2), 104-109. [Abstract] [Free Full-text]

American Lung Association Asthma Clinical Research Centers (2009) Efficacy of esomeprazole for treatment of poorly controlled asthma. New England Journal of Medicine 360(15), 1487-1499. [Abstract] [Free Full-text]

Chang, A.B., Clark, R., Sloots, T.P., et al. (2008) A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Medical Journal of Australia 189(6), 306-310. [Abstract] [Free Full-text]

de Jongste, J.C., Carraro, S., Ho, W.C., et al. (2009) Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma. American Journal of Respiratory and Critical Care Medicine 179(2), 93-97. [Abstract] [Free Full-text]

Haldar, P., Brightlin, C.E., Hargadon, B., et al. (2009) Mepolizumab and exacerbations of refractory eosinophilic asthma. New England Journal of Medicine 360(10), 973-984. [Abstract] [Free Full-text]

Holbrook, J.T., Wise, R.A., Gold, B.D. et al. (2012) Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA 307(4), 373-381. [Abstract]

Howden-Chapman, P., Pierse, N., Nicholls, S., et al. (2008) Effects of improved home heating on asthma in community dwelling children: randomised controlled trial. BMJ 337, a1411. [Abstract] [Free Full-text]

Janson, S.L., McGrath, K.W., Covington, J.K., et al. (2009) Individualized asthma self-management improves medical adherence and markers of asthma control. Journal of Allergy and Clinical Immunology 123(4), 840-846. [Abstract] [Free Full-text]

Kerwin, E.M., Oppenheimer, J.J., LaForce, C., et al. (2009) Efficacy and tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler in adults and adolescents with asthma previously stable with twice-daily budesonide/formoterol dosing. Annals of Allergy, Asthma and Immunology 103(1), 62-72. [Abstract]

Lanier, B., Bridges, T., Kulus, M., et al (2009) Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. Journal of Allergy and Clinical Immunology 124(6), 1210-1216. [Abstract]

Lemanske Jr, R.F., Mauger, D.T., Sorkness, C.A., et al. (2010) Step-up therapy for children with uncontrolled asthma while receiving inhaled corticosteroids. New England Journal of Medicine 362(11), 975-985 [Abstract] [Free Full-text]

Lenney, W., McKay, A., Tudur Smith, C., et al. (2013) Management of Asthma in School Age Children on Therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety. Health Technology Assessment 17(4), 1-218. [Abstract]

Mancuso, C.A., Choi, T.N. Westermann, H., et al. (2012) Increasing physical activity in patients with asthma through positive affect and self-affirmation: a randomized trial. Archives of Internal Medicine 172(4), 337-343. [Abstract]

Nair, P., Pizzichini, M.M., Kjarsgaard, M., et al. (2009) Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. New England Journal of Medicine 360(10), 985-993. [Abstract] [Free Full-text]

Oborne, J., Mortimer, J., Hubbard, R.B., et al. (2009) Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double blind, placebo controlled, parallel group, clinical trial. American Journal of Respiratory and Critical Care Medicine 180(7), 598-602. [Abstract] [Free Full-text]

Ryan, D., Price, D., Musgrave, S.D., et al. (2012) Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial. BMJ 344, e1756. [Abstract] [Free Full-text]

Schuh, S., Willan, A.R., Stephens, D., et al. (2009) Can montelukast shorten prednisolone therapy in children with mild to moderate acute asthma? A randomized controlled trial. Journal of Pediatrics 155(6), 795-800. [Abstract]

Skoner, D.P., Maspero, J., Banerji, D., and Ciclesonide Pediatric Growth Study Group (2008) Assessment of the long-term safety of inhaled ciclesonide on growth in children with asthma. Pediatrics 121(1), e1-14. [Abstract] [Free Full-text]

Strunk, R.C., Bacharier, L.B., Phillips, B.R., et al. (2008) Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. Journal of Allergy and Clinical Immunology 122(6), 1138-1144. [Abstract] [Free Full-text]

Strunk, R.C., Sternberg, A.L., Szefler, S.J., et al. (2009) Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. Journal of Pediatrics 154(5), 682-687. [Abstract] [Free Full-text]

Szefler, S.J., Mitchell, H., Sorkness, C.A., et al. (2008) Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet 372(9643), 1065-1072. [Abstract] [Free Full-text]

Thomas, M., McKinley, R.K., Mellor, S., et al. (2009) Breathing exercises for asthma: a randomised controlled trial. Thorax 64(1), 55-61. [Abstract] [Free Full-text]

Turpeinen, M., Nikander, K., Pelkonen, A.S., et al. (2008) Daily versus as-needed inhaled corticosteroid for mild persistent asthma (the Helsinki early intervention childhood asthma study). Archives of Disease in Childhood 93(8), 654-659. [Abstract] [Free Full-text]

Vempati, R., Bijlani, R.L., and Deepak, K.K. (2009) The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial. BMC Pulmonary Medicine 9(1), 37. [Abstract] [Free Full-text]

Vuillermin, P.J., Robertson, C.F., Carlin, J.B., et al. (2010) Parent initiated prednisolone for acute asthma in children of school age: randomised controlled crossover trial. BMJ 340, c843. [Abstract] [Free Full-text]

Wechsler, M.E., Kunselman, S.J., Chinchilli, V.M., et al. (2009) Effect of beta2-adrenergic receptor polymorphism on response to long-acting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet 374(9703), 1754-1764. [Abstract] [Free Full-text]

Wright, G.R, Howieson, S., McSharry, C., et al. (2009) Effect of improved home ventilation on asthma control and house dust mite allergen levels. Allergy 64(11), 1671-1680. [Abstract] [Free Full-text]

Observational studies published since the last revision of this topic:

Bakhireva, I.N., Schatz, M., Jones, K.L., et al. (2008) Asthma control during pregnancy and the risk of preterm delivery or impaired fetal growth. Annals of Allergy, Asthma & Immunology 101(2), 137-143. [Abstract]

Busse, W.W., Morgan, W.J., Gergen, P.J., et al. (2011) Randomized trial of omalizumab (Anti-IgE) for asthma in inner-city children. New England Journal of Medicine 364(11), 1005-1015. [Abstract] [Free Full-text]

de Vries, F., Setakis, E., Zhang, B., and van Staa, T.P. (2010) Long-acting beta2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: a study with the General Practice Research Database. European Respiratory Journal 36(3), 494-502. [Abstract] [Free Full-text]

Kelly, H.W., van Natta, M.L., Covar, R.A., et al. (2008) Effect of long-term corticosteroid use on bone mineral density in children: a prospective longitudinal assessment in the childhood asthma management program (CAMP) study. Pediatrics 122(1), e53-e61. [Abstract] [Free Full-text]

Lapi, F., Kezouh, A., Suissa, S., and Ernst, P. (2013) The use of inhaled corticosteroids and the risk of adrenal insufficiency. European Respiratory Journal 42(1), 79-86. [Abstract]

Lin, S., Munsie, J.P., Herdt-Losavio, M.L., et al. (2012) Maternal asthma medication use and risk of selected birth defects. Pediatrics 129(2), e316-e324. [Abstract]

Mai, X.M., Langhammer, A., Chen, Y., et al. (2013) Cod liver oil intake and incidence of asthma in Norwegian adults - the HUNT study. Thorax 68(1), 25-30. [Abstract]

Martinez, F.D., Chinchilli, V.M., Morgan, W.J., et al. (2011) Use of beclomethasone dipropionate as a rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 377(9766), 650-657. [Abstract]

Price, D., Musgrave, S., Wilson, E., et al. (2011) A pragmatic single-blind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines (ELEVATE study). Health Technology Assessment 15(21), 1-132. [Free Full-text]

Price, D., Musgrave, S.D., Shepstone, L., et al. (2011) Leukotriene antagonists as first-line or add-on asthma-controller therapy. New England Journal of Medicine 364(18), 1695-1707. [Abstract] [Free Full-text]

Ramsay, C.F., Pearson, D., Mildenhall, S. and Wilson, A.M. (2010) Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial. Thorax 66(1), 7-11. [Abstract]

Risnes, K.R., Belanger, K., Murk, W. and Bracken, M.B. (2010) Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1401 US children. American Journal of Epidemiology 173(3), 310-318. [Abstract] [Free Full-text]

Shaaban, R., Zureik, M., Soussan, D., et al. (2008) Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 372(9643), 1049-1057. [Abstract]

Stern, D.A., Morgan, W.J., Halonen, M., et al. (2008) Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet 372(9643), 1058-1064. [Abstract] [Free Full-text]

Tata, L.J., Lewis, S.A., McKeever, T.M., et al. (2008) Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a United Kingdom population-based study. Thorax 63(11), 981-987. [Abstract]

To, T., Gershon, A., Wang, C., et al. (2007) Persistence and remission in childhood asthma: a population-based asthma birth cohort study. Archives of Pediatrics and Adolescent Medicine 161(12), 1197-1204. [Abstract] [Free Full-text]

Vestergaard, P., Rejnmark, L., and Mosekilde, L. (2007) Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids. Chest 132(5), 1599-1607. [Abstract] [Free Full-text]

Wu, A.C., Tantisira, K., Li, L., et al. (2012) Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. American Journal of Respiratory and Critical Care Medicine 186(6), 508-513. [Abstract]

Post hoc analysis of randomized controlled trials published since the last revision of this topic:

Barr, R.G., Kurth, T., Stampfer, M.J., et al. (2007) Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study. American Journal of Respiratory and Critical Care Medicine 175(2), 120-125. [Abstract] [Free Full-text]

Kurth, T., Barra, R.G., Ganziano, J.M., and Buring, J. (2008) Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study. Thorax 63(6), 514-418. [Abstract] [Free Full-text]

New policies

No new national policies or guidelines since 1 September 2007.

New safety alerts

In September 2010, the Medicines and Healthcare products Regulatory Agency (MHRA) issued advice to prescribers that the benefits of using long-acting beta2 agonists (in conjunction with inhaled corticosteroids) in children outweigh any apparent risks. However, prescribers are advised that a daily dose of 24 micrograms formoterol should be sufficient for most children, particularly younger age-groups. Higher doses should be used rarely, and only when control is not maintained on the lower dose.

Reference: MHRA (2010) Long-acting β2-agonists: reminder for use in children and adults. Drug Safety Update 4(2), H2. [Free Full-text]

On 31 March 2009 all stock of NebuChamber® spacer devices (for use with Pulmicort inhalers®) were recalled by AstraZeneca because of reports that the mouthpiece could be attached the wrong way. This is clinically significant because the mouthpiece contains a one-way valve. Patients should be reminded that the frosted end of the mouthpiece must be attached to the spacer.

Reference: MHRA (2009) Class 2 Drug Alert (action with 48 hours): AstraZeneca UK Ltd - NebuChamber Device (Inhalation Aid) - EL(09)A/09. Medicines and Healthcare products Regulatory Agency. www.mhra.gov.uk [Free Full-text]

Changes in product availability

Pulmicort® (budesonide) 100 and 200 micrograms per dose metered dose inhalers have been discontinued (March 2011).

All strengths of the Flixotide® diskhaler have now been discontinued (December 2010). Stocks are likely to be exhausted by March 2011.

The Flixotide® 50 microgram diskhaler and all strengths of the Aerobec® breath-actuated inhaler have been discontinued.

A budesonide CFC-free inhaler (Pulmicort®) has been launched.

The Nebuhaler® spacer device (for use with Pulmicort®) has been replaced by the NebuChamber® spacer device.

Goals and outcome measures

Goals

The aim of asthma management is control of the disease with minimal side effects. Control of the disease is defined as [SIGN and BTS, 2011]:

No daytime symptoms

No night-time awakening due to asthma

No need for rescue medicine

No exacerbations

No limitations on activity including exercise

Normal lung function (in practical terms —  forced expiratory volume in 1 second (FEV1) and/or peak expiratory flow rate (PEF), greater than 80% predicted (or the person's best value if unable to attain this)

QOF indicators

Table 1 . Indicators from the Quality and Outcomes Framework (QOF) for asthma in the new General Medical Services (GMS) contract.
Quality indicator Points Threshold
AST001 The contractor establishes and maintains a register of patients with asthma, excluding patients with asthma who have been prescribed no asthma-related drugs in the preceding 12 months 4
AST002 The percentage of patients aged 8 or over with asthma (diagnosed on or after 1 April 2006), on the register, with measures of variability or reversibility recorded between 3 months before and anytime after diagnosis 15 45–80%
AST004 The percentage of patients with asthma aged 14 or over who have not attained the age of 20, on the register, in whom there is a record of smoking status in the preceding 12 months 6 45–80%
AST003 The percentage of patients with asthma, on the register, who have had an asthma review in the preceding 12 months that includes an assessment of asthma control using the 3 RCP questions 20 45–70%
SMOK002 The percentage of patients with any or any combination of the following conditions: CHD, PAD, stroke or TIA, hypertension, diabetes, COPD, CKD, asthma, schizophrenia, bipolar affective disorder or other psychoses whose notes record smoking status in the preceding 12 months 25 50–90%
SMOK005 The percentage of patients with any or any combination of the following conditions: CHD, PAD, stroke or TIA, hypertension, diabetes, COPD, CKD, asthma, schizophrenia, bipolar affective disorder or other psychoses who are recorded as current smokers who have a record of an offer of support and treatment within the preceding 12 months 25 56–96%
Data from: [BMA and NHS Employers, 2013]

QIPP - Options for local implementation

QIPP - Options for local implementation

High dose inhaled corticosteroids in asthma

Review the use of inhaled corticosteroids (ICS) routinely in patients with asthma.

Step down the dose and use of ICS where clinically appropriate in patients with asthma.

[NICE, 2013]

Background information

Definition

What is asthma?

Asthma is a chronic inflammatory condition of the airways, the cause of which is not completely understood. The airways are hyper-responsive and constrict easily in response to a wide range of stimuli. This may result in coughing, wheezing, chest tightness, and shortness of breath:

Narrowing of the airways is usually reversible (either spontaneously or with medication), leading to intermittent symptoms, but in some people with chronic asthma, the inflammation may lead to irreversible airflow obstruction.

Asthma can vary markedly in severity, clinical course, and response to treatment.

Acute asthma exacerbation is a term used to describe onset of severe asthma symptoms.

Work-aggravated asthma is pre-existing asthma that is aggravated non-specifically by dust and fumes at work.

Occupational asthma is asthma due to exposure to specific substances at work.

Exercise-induced asthma is asthma brought on by physical exertion. For most people, it is an indication of poorly controlled asthma.

[Newman Taylor, 2003; SIGN and BTS, 2011]

Prevalence

How common is asthma?

The most recent report by Asthma UK states that 5.2 million people in the UK have asthma [Asthma UK, 2006].

The prevalence of asthma has increased in most countries since the 1970s. Levels may have plateaued in some developed countries [Anderson, 2005; Rees, 2006].

The number of adults with asthma in the UK has increased by 400,000 since the last audit of UK asthma in 2001 [Asthma UK, 2006].

The proportion of adolescents aged 13–14 years reporting wheeze in the previous 12 months in Western Europe was 14.3%, and the proportion reporting severe asthma was 6.2%. Severe asthma was defined as more than four attacks of wheeze, or more than one attack of wheeze at night disturbing sleep, or more than one attack of wheeze affecting speech in the previous 12 months [Lai et al, 2009].

The proportion of children in whom asthma was diagnosed increased from 4% to 10% between 1964 and 1989 [Keeley and McKean, 2006]. A further study found a rise in the prevalence of asthmatic symptoms between 1988 and 2003 [Burr et al, 2006].

In contrast, self-reported symptoms of asthma in children 13–14 years of age decreased by about 20% in the UK between 1995 and 2002 [Anderson, 2005].

In early childhood, asthma is more common in boys than in girls, but by adulthood, the sex ratio is reversed. The mechanism for this is not clear [de Marco et al, 2000; Nicolai et al, 2003]. Approximately 60% of adults with asthma in the UK are women [Asthma UK, 2006].

More than 4.1 million GP consultations for asthma occur each year [Asthma UK, 2006].

Each year, a GP with 2000 patients will see approximately 85 people with asthma, and each of these will consult three times on average [McCormick et al, 1995].

About 2% of adults consult their GP annually with asthma [McCormick et al, 1995].

Occupational asthma may account for 9–15% of adult-onset asthma. It is reported to be the most common industrial lung disease in the developed world [SIGN and BTS, 2011].

Risk factors

What are the risk factors for asthma?

Various risk factors may increase the likelihood of development or persistence of asthma:

Family history of atopic disease (for example asthma, eczema, allergic rhinitis, or allergic conjunctivitis).

Co-existence of atopic disease.

Male sex (for pre-pubertal asthma) and female sex (for persistence of asthma from childhood to adulthood).

Bronchiolitis in infancy.

Parental smoking, including perinatal exposure to tobacco smoke.

Low birthweight (associated with intrauterine growth retardation).

Premature birth (especially in extreme-preterm infants who required ventilatory support, with consequent chronic lung disease of prematurity).

[SIGN and BTS, 2011]

Complications and prognosis

Complications

Death: more than 1400 people died of asthma in the UK in 2002. On average, one person dies of asthma every 7 hours [Asthma UK, 2006]. Asthma accounts for one of every 250 deaths worldwide [Rees, 2006].

Respiratory complications: pneumonia, pulmonary collapse (atelectasis caused by mucus plugging of the airways), respiratory failure, pneumothorax, and status asthmaticus (repeated asthma attacks without respite, or non-response to appropriate treatment).

Growth and pubertal delay in children may be a direct result of chronic disease or secondary to use of inhaled corticosteroids or repeated short courses of systemic steroids. The growth-suppressive effects of the latter may be relatively short-lived [Wolthers, 2002; Doull, 2004].

Impaired quality of life may result from suboptimal control of asthma. This may include:

Fatigue.

Underperformance and time off school or work. Asthma accounts for at least 12.7 million work days lost each year in the UK [Asthma UK, 2006].

Psychological problems, including stress, anxiety, and depression [Opolski and Wilson, 2005]. Children may experience social exclusion because they cannot participate in activities and sports.

[SIGN and BTS, 2011]

Prognosis

Male children are more likely to grow out of asthma in the transition to adulthood [SIGN and BTS, 2011].

The earlier the onset of asthma, the better the prognosis; most children who present under 2 years of age become asymptomatic by mid-childhood (6–11 years of age) [SIGN and BTS, 2011].

However, early-onset asthma in atopic children may be associated with a worse prognosis [Warner, Personal Communication, 2006].

The Melbourne Epidemiological Study of Childhood Asthma was a 1964–1999 longitudinal study that suggested that in most children with asthma, significant wheezing continued into adult life, and the more severe or frequent the symptoms in childhood, the more likely that symptoms continued [Phelan et al, 2002; Horak et al, 2003]:

This study recruited children at age 7 years and followed them up through adolescence to adulthood. The proportion of people with no recent asthma increased steadily from 20% at age 14 years to 40% at age 42 years.

Episodic asthma in childhood tends to resolve in adolescence and early adulthood.

The study concluded that the pattern of asthma during childhood predicts outcome in later life, although this is not entirely reliable.

Of note, changes in disease prevalence, environmental factors, and treatment strategies over the study may affect the interpretation of longitudinal data [Robertson, 2002].

Diagnosis

Diagnosis of asthma

Diagnosis

How do I know my patient has it?

Initially, decide how likely it is that a person has asthma.

For children, base this decision on recognizing features that increase or decrease the probability of asthma. For more information, see Probability of asthma in children.

For adults, base this decision on recognizing features that increase or decrease the probability of asthma and spirometry. For more information, see Probability of asthma in adults.

Then use clinical judgement to categorize the person into one of three groups:

High probability: diagnosis of asthma likely.

Intermediate probability: diagnosis uncertain and insufficient evidence at first consultation to make a firm diagnosis, but no features to support an alternative diagnosis.

Low probability: diagnosis other than asthma likely.

For people with an intermediate and high probability of asthma, manage as suspected asthma (to confirm or refute the diagnosis). For more information, see Scenario: New presentation of asthma.

For people with a low probability of asthma consider an alternative diagnosis.

Occupational asthma is diagnosed when the diagnosis of asthma is confirmed, the relationship between asthma and work exposure is made, and a specific cause is identified.

Exercise-induced asthma is usually diagnosed based on symptoms related to exercise.

People with exercise-induced asthma report symptoms such as coughing and wheezing after 5–10 minutes of exercise or for up to 1–2 hours after finishing exercise. The symptoms are generally worse when breathing cold or dry air (outdoors), or with longer duration or higher intensity of exercise.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Probability of asthma in children

What features increase or decrease the probability of asthma in children?

Features that increase the probability of asthma in children include:

More than one of the following symptoms: wheeze, cough, difficulty breathing, chest tightness. Such symptoms particularly indicate asthma if they:

Are frequent and recurrent.

Are worse at night and in the early morning.

Occur in response to, or are worse after, exercise or other triggers such as exposure to pets, cold or damp air, or with emotions or laughter.

Occur even when the person has not got a cold (coryzal illness).

Personal history of another atopic disorder (hayfever, eczema).

Family history of asthma and/or atopic disorder.

Widespread wheeze (bilateral, predominantly expiratory).

The absence of wheeze does not rule out asthma. In severe cases, chest wall movement may be reduced on both sides, and wheeze may not be audible.

Prolonged expiration.

Increased respiratory rate.

Features that lower the probability of asthma in children include:

Symptoms with colds (coryzal illness) only.

Isolated cough in the absence of wheeze or difficulty breathing.

History of moist cough.

Prominent dizziness, light-headedness, peripheral tingling.

Clinical features pointing to an alternative diagnosis.

Repeatedly normal physical examination of the chest when symptomatic.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Probability of asthma in adults

What features increase or decrease the probability of asthma in adults?

Features that increase the probability of asthma in adults include:

More than one of the following symptoms: wheeze, breathlessness, chest tightness, and cough, particularly if they:

Are worse at night and in the early morning.

Occur in response to exercise, allergen exposure, and cold air.

Occur after taking aspirin or beta-blockers.

History of atopic disorder.

Family history of asthma and/or atopic disorder.

Widespread wheeze (bilateral, predominantly expiratory).

The absence of wheeze does not rule out asthma. In severe cases, chest wall movement may be reduced on both sides, and wheeze may not be audible.

Prolonged expiration.

Increased respiratory rate.

Features that lower the probability of asthma in adults include:

Prominent dizziness, light-headedness, peripheral tingling.

Chronic productive cough in the absence of wheeze or breathlessness.

Voice disturbance.

Symptoms with colds only.

Significant smoking history (greater than 20 pack-years).

Cardiac disease.

Repeatedly normal physical examination of the chest when symptomatic.

Clinical features of an alternative diagnosis.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Spirometry

When should I investigate with spirometry?

Spirometry is the preferred method to demonstrate airway obstruction because:

It more clearly identifies airway obstruction than peak expiratory flow (PEF), and the results are less dependent on effort.

PEF variability can be increased in people with conditions commonly confused with asthma.

PEF should only be used if spirometry is unavailable.

In view of the potential requirement for treatment over many years, it is important even in relatively clear cut cases, to try to obtain objective support for the diagnosis of asthma.

Adults

Perform spirometry on all adults to assess for the presence and severity of airway obstruction.

Airway obstruction is confirmed when forced expiratory volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio is less than 0.7.

Whether or not spirometry should happen before starting treatment depends on the certainty of the initial diagnosis and the severity of the presenting symptoms.

Normal spirometry obtained when a person is asymptomatic does not exclude a diagnosis of asthma. Repeated assessment and measurement may be necessary.

Children

Spirometry is recommended for children with an intermediate probability of asthma if they are able to perform the test (usually older than 5 years).

Spirographs require calibration to allow accurate interpretation of the results (for example Rosenthal normal values based on the child's sex and height). Health care professionals require training on how to calibrate and interpret the results from a spirogram. CKS recommend that advice should be sought regarding carrying out spirometry in children and interpreting the results, unless the healthcare professional has received the appropriate training.

Measuring lung function in young children is difficult and not usually possible in children under 5 years of age.

Normal results obtained when the child is asymptomatic do not exclude a diagnosis of asthma.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Trigger factors

What are the trigger factors?

Respiratory infections, most commonly viruses. Fungi, bacteria, or parasites may be responsible in some people.

Allergens, such as pollen, dust mites, and feathered or furry animals.

Airborne irritants, such as cigarette smoke, irritant dusts, cold air, vapours and fumes, atmospheric pollution.

Weather changes, such as cold air.

Exercise.

Emotional factors, such as stress or laughing.

Gastro-oesophageal reflux disease.

Allergic rhinitis and sinusitis.

Occupational sensitizers, such as isocyanates.

Drugs, such as nonsteroidal anti-inflammatory drugs and beta-blockers.

Foods containing sulphites, such as beer, wine, and shrimps.

Basis for recommendation

Basis for recommendation

This information is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011] and a strategy for asthma management and prevention from the Global Initiative for Asthma [GINA, 2006].

Differential diagnosis in children

What else might it be in children?

In young children with episodic breathlessness, wheeze, and cough, the most likely alternative diagnosis to asthma is viral-induced wheeze.

Other causes of persistent symptoms of breathlessness, wheeze, or cough:

Allergic bronchopulmonary aspergillosis, allergic alveolitis, hypersensitivity pneumonitis, polyarteritis nodosa.

Cystic fibrosis, chronic lung disease, ciliary dyskinesia, developmental anomaly (vascular ring) and other malformations affecting airway calibre, bronchopulmonary dysplasia.

Laryngeal disorder, laryngo-tracheomalacia, tracheo-oesophageal fistula.

Gastro-oesophageal reflux disease with or without aspiration, swallowing problems with aspiration.

Congestive heart failure, pulmonary thromboembolism, sarcoidosis.

Tumour, lymphoma with superior vena cava obstruction, neuromuscular disorder, immune deficiency.

Psychogenic cough.

Other causes of acute onset of breathlessness:

Inhaled foreign body.

Viral-associated wheeze of infancy, bronchiolitis, pneumonia, croup, bronchitis, pertussis.

Sinusitis.

Post-nasal drip.

Bronchiectasis.

Post-infection syndrome (bronchiolitis obliterans).

Tuberculosis.

Histoplasmosis.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Differential diagnosis in adults

What else might it be in adults?

In adults, alternative diagnoses can be classified according to the presence or absence of airways obstruction:

Conditions without airways obstruction:

Chronic cough syndromes

Hyperventilation syndrome

Vocal cord dysfunction

Rhinitis

Gastro-oesophageal reflux

Heart failure

Pulmonary fibrosis

Conditions with airways obstruction:

Chronic obstructive pulmonary disease

Bronchiectasis

Inhaled foreign body

Obliterative bronchiolitis

Large airway stenosis

Lung cancer

Sarcoidosis

† May also be associated with non-obstructive spirometry.

Basis for recommendation

Basis for recommendation

This recommendation is based on a British guideline on the management of asthma: a national clinical guideline, from the Scottish Intercollegiate Guidelines Network and the British Thoracic Society [SIGN and BTS, 2011].

Management

Management

Scenario: New presentation of asthma : covers the management of adults and children with a new presentation of asthma and who have a high, intermediate or low probability of having asthma.

Scenario: Uncontrolled asthma on current treatment : covers how to step up asthma therapy in adults and children with uncontrolled asthma.

Scenario: Controlled asthma on current treatment : covers how to follow up people with asthma and when to consider stepping down asthma therapy.

Scenario: Acute asthma exacerbation : covers how to assess someone with acute asthma, when admission to hospital is required, and how to manage people with acute asthma who do not require hospital admission.

Scenario: Management of exercise-induced asthma : covers the management of people with exercise induced asthma.

Scenario: Suspected occupational asthma : covers the management of occupational asthma.

Scenario: Pregnancy and breastfeeding : covers the management of asthma in a pregnant or breastfeeding woman.

Scenario: New presentation of asthma

Scenario: New presentation of asthma

1months3060monthsBoth

Managing children with suspected asthma

Managing children with suspected asthma

Managing children with a low probability of asthma

How should I manage children with a low probability of asthma?

Consider an alternative diagnosis, or refer to secondary care for further investigations.

Basis for recommendation

Basis for recommendation

This recommendation is based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Managing children with a high probability of asthma

How should I manage children with a high probability of asthma?

Start a trial of asthma treatment for 2–3 months. The choice of treatment depends on the severity and frequency of symptoms. For more information, see Starting asthma treatment.

If response is good, continue treatment.

If response is poor:

Assess compliance and inhaler technique.

Consider checking airway reversibility, or refer to secondary care for additional tests.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Managing children with an intermediate probability (cannot perform airway obstruction tests)

How should I manage children with an intermediate probability of asthma who cannot perform airway obstruction tests?

The following options may be tried depending on the frequency and severity of symptoms:

Watchful waiting — review the child after a time interval agreed with the parents or carers. In children with mild, intermittent wheeze and other respiratory symptoms which occur only with viral upper respiratory tract infections, it is reasonable to give no specific treatment and then review the child.

Start a trial of asthma treatment for 2–3 months. The choice of treatment depends upon the severity and frequency of symptoms:

If response is good, continue treatment.

If response is poor, assess compliance and inhaler technique, and consider referral for Additional tests in secondary care.

If it is unclear whether a child has improved, careful observation during a trial of treatment withdrawal may clarify whether they have responded to asthma treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Measuring lung function in young children is difficult and not usually possible in children younger than 5 years of age.

Although a trial of treatment with inhaled or oral steroids is often used to make a diagnosis there is little objective evidence to support this approach in children who present with a history of recurrent wheeze.

Managing children with an intermediate probability of asthma (can perform airway obstruction tests)

How should I manage children with an intermediate probability of asthma who can perform airway obstruction tests?

Check for airway obstruction using spirometry:

Spirometry should be done by a trained healthcare professional; if this is not possible, seek advice.

Normal spirometry results obtained when the child is asymptomatic do not exclude a diagnosis of asthma. Repeated measurements of lung function may be more helpful to interpret than a single measurement.

If there is no evidence of airway obstruction, consider referring for Additional tests in secondary care.

If there is evidence of airway obstruction, assess for reversibility to either bronchodilator therapy (for example salbutamol 400 micrograms via metered-dose inhaler and spacer) and/or to a trial of asthma treatment for 2–3 months:

If there is significant reversibility (greater than 12% increase in forced expiratory volume in 1 second [FEV1]), or if there is a significant increase in peak expiratory flow rate after a bronchodilator, a diagnosis of asthma is probable. Continue to treat as asthma. The choice of asthma treatment (for example inhaled short-acting beta2-agonist or inhaled corticosteroid) depends on the severity and frequency of symptoms. For more information, see Starting asthma treatment.

If there is no significant reversibility (less than 12% increase in FEV1), and a trial of treatment is not beneficial, refer to secondary care for additional tests.

If it is unclear whether a child has improved on a trial of asthma treatment, careful observation during a trial of treatment withdrawal may clarify whether they have responded to asthma treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

In children, tests of airway obstruction (spirometry or measuring peak expiratory flow) may provide support for a diagnosis of asthma.

Spirographs require calibration to allow accurate interpretation of the results (for example Rosenthal normal values based on the child's sex and height). Healthcare professionals require training on how to calibrate and interpret the results from a spirogram. CKS recommend that advice should be sought regarding carrying out spirometry in children and interpreting the results, unless the healthcare professional has received appropriate training.

Although a trial of treatment with inhaled or oral steroids is often used to make a diagnosis there is little objective evidence to support this approach in children who present with a history of recurrent wheeze.

Starting asthma treatment

How should I start treatment for asthma?

Explain that lifestyle changes and medication are meant to control asthma symptoms and prevent an exacerbation.

Explain the difference between reliever and preventive therapy, and demonstrate how to use inhalers and spacer devices.

Prescribe an effective delivery device on the basis of convenience, cost, and suitability.

Prescribe a short-acting beta2-agonist for use as required to treat daytime symptoms (twice weekly or less often) of short duration (lasting only a few hours).

Prescribe a regular inhaled corticosteroid with the short-acting beta2-agonist if symptoms are at least three times weekly, or waking the person one night weekly.

Prescribe a peak flow meter and record the person's best peak expiratory flow rate reading. Advise monitoring during an exacerbation, worsening symptoms, or a medication change. Regular monitoring of peak expiratory flow is no longer advised as it does not provide additional benefit when added to a symptom based management strategy.

Provide education about asthma, such as how to monitor symptoms and recognize an exacerbation.

Additional information

Additional information

Demonstrate how to use inhalers and spacer devices. Ask the person to repeat the technique back to you. For more information on how to use inhalers (with demonstrations), see www.asthma.org.uk or www.ginasthma.org.

Encourage monitoring of asthma control on the basis of symptoms [SIGN and BTS, 2011]:

Symptoms that worsen at night, or exercise-induced asthma, may suggest poor asthma control. The frequency of short-acting beta2-agonist use is a useful guide to asthma control. Ideally, people should not be using reliever medication in controlled asthma.

Do not recommend routine monitoring of peak expiratory flow rate (PEFR) unless the person has severe asthma or a poor perception of bronchoconstriction [SIGN and BTS, 2011]. However, encourage measuring PEFR as part of a self management programme: loss of asthma control may be assessed by symptoms or by measuring PEFR or both [SIGN and BTS, 2011].

Ideally, record PEFR annually in children whilst they are still growing [Pinnock and Shah, 2007].

A short-acting beta2-agonist should be started on an as required basis for mild, intermittent symptoms. People should have normal lung function and no nocturnal awakening. When symptoms are more frequent or are worsening, people require treatment at a level based on the severity of symptoms. See Scenario: Uncontrolled asthma on current treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Measuring peak expiratory flow rate (PEFR): The guideline development group for the British guideline on the management of asthma: a national clinical guideline commented that studies in children have shown that routine serial measurements of PEFR do not provide additional useful information when added to a symptom based management strategy [SIGN and BTS, 2011].

Short-acting bronchodilators: inhaled short-acting beta2-agonists are the preferred treatment for rapid symptom relief. The evidence suggests that short-acting beta2-agonists have a quicker onset of action and fewer adverse effects than other reliever drugs (inhaled anticholinergics, short-acting oral beta2-agonists, and short-acting theophylline). An as required regimen is at least as effective as regular use in people with asthma [GINA, 2006].

Managing adults with suspected asthma

Managing adults with suspected asthma

Managing adults with a low probability of asthma

How should I manage adults with a low probability of asthma?

Consider an alternative diagnosis, or refer to secondary care for further investigations.

Basis for recommendation

Basis for recommendation

This recommendation is based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Managing adults with a high probability of asthma

How should I manage adults with a high probability of asthma?

Start a trial of asthma treatment for 2–3 months. The choice of treatment depends on the severity and frequency of symptoms. For more information, see Starting asthma treatment.

If response is good, continue treatment.

If response is poor:

Assess compliance and inhaler technique.

Consider checking airway reversibility (in addition to spirometry at the initial diagnosis), or refer to secondary care for additional tests.

Assessing adults for airway reversibility

Assessing adults for airway reversibility

Assess forced expiratory volume in 1 second (FEV1) and/or symptoms before and 15 minutes after inhalation of a short-acting beta2-agonist (salbutamol 400 micrograms by metered-dose inhaler delivered via a spacer, or 2.5 mg by nebulizer) at the time of assessment. A greater than 400 mL improvement in FEV1 strongly suggests underlying asthma.

If response to inhaled salbutamol is incomplete, assess FEV1 after either inhaled corticosteroids (beclometasone equivalent 200 micrograms twice daily for 6–8 weeks) or oral prednisolone (30 mg/day for 14 days).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Managing adults with an intermediate probability of asthma

How should I manage adults with an intermediate probability of asthma?

If the person has an intermediate probability of asthma, consider performing a reversibility test (in addition to spirometry at the initial diagnosis) and/or a trial of treatment for 2–3 months:

If a trial of treatment is offered, the choice of treatment depends on the severity and frequency of symptoms (see Starting asthma treatment).

If a reversibility test shows significant reversibility (a greater than 400 mL improvement in forced expiratory volume in 1 second [FEV1]), start a trial of asthma treatment.

If a reversibility test shows no reversibility (less than 400 mL improvement in FEV1), consider referring to secondary care for additional tests.

If a trial of asthma treatment has been started and:

Response is good, continue treatment.

Response is poor, check for reversibility. If there is insignificant reversibility, consider referring to secondary care for additional tests. If there is significant reversibility, assess compliance and inhaler technique.

Assessing adults for airway reversibility

Assessing adults for airway reversibility

Assess forced expiratory volume in 1 second (FEV1) and/or symptoms before and 15 minutes after inhalation of a short-acting beta2-agonist (salbutamol 400 micrograms by metered-dose inhaler delivered via a spacer, or 2.5 mg by nebulizer) at the time of assessment. A greater than 400 mL improvement in FEV1 strongly suggests underlying asthma.

If response to inhaled salbutamol is incomplete, assess FEV1 after either inhaled corticosteroids (beclometasone equivalent 200 micrograms twice daily for 6–8 weeks) or oral prednisolone (30 mg/day for 14 days).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Starting asthma treatment

How should I start treatment for asthma?

Explain that lifestyle changes and medication are meant to control asthma symptoms and prevent an exacerbation.

Explain the difference between reliever and preventive therapy, and demonstrate how to use inhalers and spacer devices.

Prescribe an effective delivery device on the basis of convenience, cost, and suitability.

Prescribe a short-acting beta2-agonist for use as required to treat daytime symptoms (twice weekly or less often) of short duration (lasting only a few hours).

Prescribe a regular inhaled corticosteroid with the short-acting beta2-agonist if symptoms are at least three times weekly, or waking the person one night weekly.

Prescribe a peak flow meter, record the person's best peak expiratory flow rate reading, and advise monitoring during an exacerbation, worsening symptoms, or a medication change. Regular monitoring of peak expiratory flow is no longer advised as it does not provide additional benefit when added to a symptom based management strategy. However, adults with severe disease or who have a poor perception of bronchoconstriction may benefit from regular peak expiratory flow rate monitoring.

Provide self-management information about asthma, such as how to monitor symptoms and recognize an exacerbation.

Additional information

Additional information

Demonstrate how to use inhalers and spacer devices. Ask the person to repeat the technique back to you. For more information on how to use inhalers (with demonstrations), see www.asthma.org.uk or www.ginasthma.org.

Encourage monitoring of asthma control on the basis of symptoms [SIGN and BTS, 2011]:

Symptoms that worsen at night, or exercise-induced asthma, may suggest poor asthma control. The frequency of short-acting beta2-agonist use is a useful guide to asthma control. Ideally, people should not be using reliever medication in controlled asthma.

Do not recommend routine monitoring of peak expiratory flow rate (PEFR) unless the person has severe asthma or a poor perception of bronchoconstriction [SIGN and BTS, 2011]. However, encourage measuring PEFR as part of a self management programme: loss of asthma control may be assessed by symptoms or by measuring PEFR or both [SIGN and BTS, 2011].

A short-acting beta2-agonist should be started on an as required basis for mild, intermittent symptoms. People should have normal lung function and no nocturnal awakening. When symptoms are more frequent or are worsening, people require treatment at a level based on the severity of symptoms. See Scenario: Uncontrolled asthma on current treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Measuring peak expiratory flow rate (PEFR): The guideline development group for the British Guideline on the Management of Asthma: a national clinical guideline commented that in most adults with asthma, symptom-based monitoring is adequate [SIGN and BTS, 2011].

Short-acting bronchodilators: inhaled short-acting beta2-agonists are the preferred treatment for rapid symptom relief. The evidence suggests that short-acting beta2-agonists have a quicker onset of action and fewer adverse effects than other reliever drugs (inhaled anticholinergics, short-acting oral beta2-agonists, and short-acting theophylline). An as required regimen is at least as effective as regular use in people with asthma [GINA, 2006].

Key prescribing information

Key prescribing information

Choosing a delivery device

Which delivery device should I prescribe?

When choosing an inhaler device for a person with asthma, consider:

The availability of the drug and dose in the specific device.

The ability of the person to develop and maintain an effective technique with the specific device — this may depend on such factors as age, dexterity, coordination, and inspiratory flow.

The suitability of the device to the person's (and carer's) lifestyles, considering such factors as portability and convenience.

The person's preference for and willingness to use a particular device.

Cost — choose the device with the lowest overall cost (taking into account daily required dose and product price per dose).

Good technique is essential in ensuring the correct use of inhaler devices. Only prescribe inhalers after the person using them (or their carer) has received training in the use of the device and has demonstrated acceptable technique.

Additional information

Additional information

A wide variety of devices, masks, and spacers are used to deliver inhaled drugs, including:

Pressurized metered-dose inhalers.

Breath-actuated metered-dose inhalers.

Dry-powder inhalers.

Spacer devices with a variety of different volumes.

Face masks with a variety of designs.

Nebulizers, driven by air or oxygen.

For a full list of available devices, see www.bnf.org.

Prescribers should familiarize themselves with a selection of these devices so they can inform, supervise, and assist patients appropriately.

Dry-powder devices and breath-actuated metered-dose inhalers require an inspiratory flow of at least 30 L/min to activate the device. Some frail people and younger children cannot consistently achieve the required minimum inspiratory flow rate [NICE, 2002].

Table 1 shows suggested minimum age requirements for the correct use of inhaled drug delivery devices.

Table 1 . Age requirements for correct use of inhaler delivery devices.
Delivery system Minimum age
pMDI > 5 years
pMDI with spacer > 4 years
pMDI with spacer and mask 4 years or younger
Breath-actuated metered-dose inhaler > 5 years
Dry-powder inhaler 5 years or older
pMDI = pressurized metered-dose inhaler.

Basis for recommendation

Basis for recommendation

A number of factors guiding the choice of inhaler device have been identified in the literature [MeReC, 2002; Dolovich et al, 2005; SIGN and BTS, 2011].

Systematic reviews have found no evidence that alternative inhaler devices are clinically more effective than standard pressurized metered-dose inhalers (pMDIs) for delivering beta2-agonist bronchodilators or inhaled corticosteroids [Brocklebank et al, 2001; Ram et al, 2001]. On this basis, if used correctly, pMDIs are the most cost-effective inhaler devices:

Studies often select for people who can use each of the devices appropriately, or they provide intensive training to ensure that the appropriate technique is used [Dolovich et al, 2005]. Therefore, in practice, efficacy may differ among individuals.

Delivery systems for adults

Which delivery system is recommended for adults?

A pressurized metered-dose inhaler (pMDI) with or without a spacer device is recommended for delivery of inhaled corticosteroids and bronchodilators in adults, provided that the person can use the method adequately.

A dry-powder inhaler (DPI) or a breath-actuated metered-dose inhaler may be more acceptable to people who are unable or unwilling to use a standard pMDI and spacer:

Because large-volume spacer devices are not easily portable, a DPI or a breath-actuated metered-dose inhaler (which are smaller and therefore more portable) may be appropriate for bronchodilator (reliever) use during the day or when travelling.

Using such a device for portable bronchodilation does not necessitate use of the same device for inhaled corticosteroid treatment or for bronchodilator treatment at home.

Nebulizers are rarely required for the routine management of asthma in primary care:

If available, a nebulizer may be used in a severe exacerbation of asthma for the combined delivery of short-acting bronchodilators and anticholinergic drugs.

Basis for recommendation

Basis for recommendation

Good evidence from systematic reviews shows that, when used correctly, pressurized metered-dose inhalers (pMDIs) and alternative inhaler devices do not differ clinically in effectiveness [Brocklebank et al, 2001; Ram et al, 2001]. The pMDIs are generally less expensive than alternative inhaler devices.

Up to 70% of people cannot use a pMDI correctly. A common problem is the timing of actuation with inspiration [Giraud and Roche, 2002; Molimard et al, 2003]. Use of a spacer with a pMDI largely overcomes problems with poor technique.

Delivery system for children 5 to 15 years

Which delivery system is recommended for children aged 5 to 15 years?

A pressurized metered-dose inhaler (pMDI) with a suitable spacer device is recommended for the delivery of inhaled corticosteroids.

If the child's use of the pMDI and spacer is likely to be so poor as to undermine effective asthma control, consider alternative devices (e.g. dry-powder inhaler [DPI] or breath-actuated metered-dose inhaler [MDI]), bearing in mind the need to minimize the adverse effects of corticosteroids.

For bronchodilators, consider a wider range of devices (for example DPI, breath-actuated MDI), which allow for more frequent spontaneous use and greater portability.

Basis for recommendation

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence guidance Inhaler devices for routine treatment of chronic asthma in older children (aged 5–15 years), and are based on findings from limited evidence, clinical opinion, and pharmacological considerations [NICE, 2002].

Delivery system for children under 5 years

Which delivery system is recommended for children younger than 5 years?

A pressurized metered-dose inhaler (pMDI) plus suitable spacer device, with a face mask where necessary, is recommended for the delivery of inhaled corticosteroid and bronchodilators in children younger than 5 years.

A face mask is required until the child can breathe reproducibly using the spacer mouthpiece. Most children older than 3 years can use a mouthpiece.

If this is not clinically effective for the child, consider nebulized therapy. Few children younger than 5 years can use a dry-powder inhaler adequately.

Basis for recommendation

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence, Guidance on the use of inhaler systems in children under the age of 5 years with chronic asthma, and are based on limited evidence from small, poor-quality studies [NICE, 2000].

When to use a spacer device

When should a spacer device be used?

A large-volume spacer is recommended for the administration of inhaled corticosteroids in all children younger than 16 years, and for giving high doses of inhaled corticosteroids (> 800 micrograms of beclometasone or equivalent daily) in adults.

Consider spacer devices for people who have difficulty coordinating actuation of a pressurized metered-dose inhaler with inhalation.

Use a pressurized metered-dose inhaler plus a large-volume spacer device as an alternative to a nebulizer in an acute exacerbation of asthma. See Scenario: Acute asthma exacerbation for more information.

Basis for recommendation

Basis for recommendation

By filtering out larger particles, large-volume spacer devices reduce oropharyngeal deposition of the drug and the amount of drug absorbed from the gastrointestinal tract at all doses [DTB, 2000]. This is particularly important for inhaled corticosteroids because:

Reducing oropharyngeal deposition of inhaled corticosteroids decreases the incidence of local adverse effects, such as oral candidiasis.

Reducing the amount of drug absorbed from the gut reduces the risk of systemic adverse effects.

Choice of spacer device

Which spacer device should I prescribe?

Where possible, prescribe the spacer that the manufacturer recommends as suitable for use with the particular pressurized metered-dose inhaler.

Table 1 shows which spacer devices are compatible with which pressurized metered-dose inhalers.

Table 1 . Specific compatibilities of pressurized metered-dose inhalers (pMDIs) and spacer devices.
pMDI Spacer recommended
Bronchodilator Corticosteroid
Airomir® (salbutamol) Atrovent® (ipatropium) Qvar® (beclometasone) Alvesco® (ciclesonide) AeroChamber Plus®
Ventolin Evohaler® (salbutamol) Serevnt Evohaler® (salmeterol) Clenil Modulite® (beclometasone) Flixotide Evohaler® (fluticasone) Volumatic®
Data from: [BNF 53, 2007]

Basis for recommendation

Basis for recommendation

The Committee on the Safety of Medicines has raised concerns that drug delivery to the lung may be changed if alternative spacer devices are used [MHRA, 2006b]. This is most likely to be clinically significant with high-dose inhaled corticosteroids.

Advice on using a spacer device

What advice should I give regarding using the spacer device?

Drugs should be administered as single actuations into the spacer and inhaled with minimum delay after each actuation, repeating until the prescribed number of puffs has been given. The canister should be shaken between actuations.

When multiple puffs are being given, as during exacerbations, there should be a short pause between puffs to avoid hyperventilation.

Spacer devices should be washed before they are first used, and once a month thereafter. They should be replaced every 6–12 months.

Plastic or polycarbonate spacers (including Volumatic®, AeroChamber®, and Nebuhaler®) should be washed in washing-up liquid and allowed to air-dry (without rinsing or wiping). Any residual detergent should be wiped from the mouthpiece.

Basis for recommendation

Basis for recommendation

This recommendation is based on expert opinion in a review article [DTB, 2000].

Multiple actuations of the metered-dose inhaler into the spacer before inhalation may reduce the proportion of the drug inhaled [DTB, 2000].

Static charge builds up on the walls of the spacer, potentially reducing the output of medication from the spacer. Washing the spacer as advised reduces this charge for at least 4 weeks, increasing the delivery of drug to the lungs [DTB, 2000].

Role of combination inhalers

What is the role of combination inhalers in asthma?

In general, inhaled corticosteroid/long-acting beta2-agonist (LABA) combination inhalers are recommended in preference to an inhaled steroid and a long-acting beta2 agonist in separate inhalers. Combination inhalers should be used in people who are stabilized on the component drugs in the same dose ratio. A combination inhaler is recommended to:

Guarantee that the long-acting beta2-agonist is not taken without an inhaled steroid.

Improve adherence.

Three combined products are available in the UK:

Symbicort® is a combination of budesonide and formoterol delivered as a dry-powder inhaler.

Seretide® is a combination of fluticasone and salmeterol and is delivered by a dry-powder inhaler or pressurized metered-dose inhaler (pMDI).

Fostair® is a combination of beclometasone and formoterol delivered as a CFC-free pMDI. It is licensed for use only in adults aged 18 years and older. It is not dose equivalent to beclometasone delivered by CFC pMDI; Fostair® 100/6 may be substituted for Clenil Modulite® (CFC-free beclometasone pMDI) at 1:2 dosing.

The Symbicort SMART® regimen (a combination inhaler as maintenance and reliever therapy) may be considered in adults who respond to LABAs but still have inadequate control of their asthma (step 3).

Basis for recommendation

Basis for recommendation

Provided adherence is good, efficacy and adverse effects do not differ according to whether inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) for maintenance therapy are given in combination or in separate inhalers [SIGN and BTS, 2011].

In clinical practice, however, combination inhalers may improve adherence. Combination inhalers are therefore recommended by the National Institute for Health and Clinical Excellence [NICE, 2008] and the Medicines and Healthcare products Regulatory Agency [MHRA, 2008] as they:

Guarantee that the long-acting beta2-agonist is not taken without an inhaled corticosteroid. There is therefore a lower risk of serious asthma-related adverse effects, which can occur when a LABA inhaler is used on its own.

Improve adherence to drug treatment, as fewer inhalations and inhaler devices are needed [Currie et al, 2005]. However, no direct evidence substantiates this theory.

The main disadvantage of the combination inhalers is that the doses of the component drugs cannot be individually titrated without changing the inhaler (e.g. during stepping-up or stepping-down of ICS). This is more easily done with separate inhalers.

There is evidence that using the combination inhaler, Symbicort® (budesonide and formoterol) as a maintenance and reliever therapy (Symbicort SMART®) is similarly effective to conventional methods at reducing exacerbation rates in people with moderate to severe asthma symptoms. It is recommended for use as Step 3 of the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Referral

When is a referral recommended in people with asthma?

The decision to refer is influenced by local referral pathways, the individual, and the experience of the primary healthcare provider.

In addition to respiratory physicians and paediatricians with a specialist interest in respiratory medicine, such specialists as dietitians, physiotherapists, occupational therapists, and respiratory nurse specialists may be involved in the management of asthma at any stage.

Admit or refer adults for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt:

Unexpected clinical findings (for example crackles, clubbing, cyanosis, cardiac disease).

Persistent non-variable breathlessness.

Monophonic, unilateral or fixed wheeze or stridor.

Persistent chest pain or atypical features.

Prominent systemic features (for example weight loss, myalgia, fever).

Persistent cough or sputum production.

Spirometric or peak expiratory flow measurements that do not fit the clinical picture (for example unexplained restrictive spirometry).

Suspected occupational asthma.

Non-resolving pneumonia.

Inadequate response to maximum guideline treatment.

Admit or refer children for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt (the younger the child, the more difficult it is to be sure that wheezing is due to asthma):

Unexpected clinical findings (for example abnormal voice, focal chest signs, dysphagia, inspiratory wheeze, stridor).

Symptoms present from birth, or perinatal lung problem.

Excessive vomiting or posseting.

Severe upper respiratory tract infection.

Persistent productive cough.

Family history of unusual chest disease.

Failure to thrive.

Parental anxiety.

Inadequate response to maximum guideline treatment, particularly if oral corticosteroids are needed frequently, or use of the maximum dose of inhaled corticosteroids.

The urgency of a referral to secondary care or admission to hospital should be appropriate to the clinical situation.

For indications of when to admit someone with an acute exacerbation of asthma, see When to admit to hospital in Scenario: Acute asthma exacerbation.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Additional tests in secondary care

What additional tests are available in secondary care?

Other tests available in secondary care include:

Indirect testing for bronchoconstriction, for example more than 15% decrease in the forced expiratory value in 1 second after 6 minutes of running.

Testing for bronchial hyper-responsiveness using histamine or methacholine.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006a].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2011].

Scenario: Uncontrolled asthma on current treatment

Scenario: Uncontrolled asthma on current treatment

1months3060monthsBoth

Management in child under 5 years

Children under 5 years of age with uncontrolled symptoms on current treatment: How do I manage?

Adjust treatment using the step-wise approach outlined below.

Before starting a new drug or stepping up treatment, confirm with the parents their understanding of the role of treatment, adherence to treatment, inhaler technique, and appropriate elimination of trigger factors.

Choose an effective delivery device on the basis of convenience, cost, and suitability:

Step 1: Prescribe a short-acting beta2-agonist to all children, for rapid symptom relief.

Step 2: Consider starting an inhaled corticosteroid (ICS) at a dose that is appropriate for the severity of symptoms (usually equivalent to beclometasone CFC-free as Clenil Modulite® 200 to 400 micrograms/day). Indications for ICS include:

Having symptoms three times weekly or more, or

Awakening with symptoms one night weekly or more, or

Having an exacerbation in the last 2 years, or

Using inhaled short-acting beta2-agonist three times weekly or more.

If ICS are not tolerated or are contraindicated, consider starting a leukotriene receptor antagonist at step 2 (but do so only in children aged 2–5 years).

Step 3: If the child still has symptoms while using regular ICS (equivalent to Clenil Modulite® [beclometasone CFC-free] 400 micrograms/day), consider:

For children younger than 2 years: move to step 4.

For children aged 2–5 years: initiate a trial of a leukotriene receptor antagonist; if asthma remains inadequately controlled, move to step 4.

Step 4: Refer to a paediatrician with knowledge about respiratory diseases.

Offer self-management information, including written action plans focusing on the child's and the family's needs.

Additional information

Additional information

Inhaled corticosteroids should be used twice a day, at the lowest dose that maintains effective control of asthma. Higher doses may be needed in young children to ensure adequate drug delivery.

Leukotriene receptor antagonists: montelukast is the only drug in this class that is licensed for use in children 2–5 years of age.

Choose an effective delivery system on the basis of availability, the child's ability to use the device, convenience, and cost. For details, see Delivery system for children under 5 years.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Evidence is limited for all types of treatment for asthma in children younger than 5 years compared with older children and adults.

Inhaled corticosteroids (ICS): the evidence now suggests that ICS are safe and effective in younger children. These agents are beneficial even in mild asthma, but there is no benefit in starting treatment at very high doses and then stepping down. Concerns remain about the adverse effects of ICS in children.

Management in child 5-12 years

Children aged 5-12 years with uncontrolled symptoms on current treatment: How do I manage?

Adjust treatment using the step-wise approach outlined below.

Before starting a new drug or stepping up treatment, confirm with the parents their understanding of the role of treatment, adherence to treatment, inhaler technique, and appropriate elimination of trigger factors.

Choose an effective delivery device on the basis of convenience, cost, and suitability:

Step 1: Prescribe a short-acting beta2-agonist to all children with asthma, for rapid symptom relief.

Step 2: Consider starting an inhaled corticosteroid (ICS) at a dose most appropriate to the severity of symptoms; for beclometasone CFC-free as Clenil Modulite® this is 200 to 400 micrograms/day. Indications include:

Having symptoms three times weekly or more, or

Awakening with symptoms one night a week or more, or

Having an exacerbation in the past 2 years, or

Using their inhaled beta2-agonist three times weekly or more.

If ICS therapy is not tolerated, consider starting a leukotriene receptor antagonist or cromones. Long-acting beta2-agonists (LABA) should only be prescribed with an ICS and therefore should not be considered an alternative to ICS.

Step 3: Consider starting Long-acting beta2-agonists (LABA) if symptoms are still uncontrolled when using an ICS at 400 micrograms/day:

If the child has a good response to the LABA with adequate symptom control, continue the LABA and current dose of the ICS. Consider prescribing a combination inhaler.

If the child has a good response to the LABA but symptom control is still inadequate, and the child is receiving 400 micrograms/day of an ICS, continue the LABA and go to step 4.

If the child does not respond to LABA, stop the LABA. If the symptom control is inadequate and the child is receiving 400 micrograms/day of an ICS, then consider an alternative add-on treatment, such as a leukotriene receptor antagonist or modified-release theophylline, before moving to step 4.

Step 4: Consider increasing the ICS to the maximum recommended daily dose. For beclometasone CFC-free as Clenil Modulite® this is 800 micrograms/day. Children under specialist care may benefit from a trial of a dose of ICS above 800 micrograms a day before moving to step 5.

Step 5: Refer to a paediatrician with knowledge of respiratory medicine. Continuous or frequent use of oral corticosteroids may be needed. Omalizumab may be initiated by some specialists for children with severe, persistent, allergic asthma.

Offer self-management information, including written action plans focusing on the individual's needs.

Additional information

Additional information

The duration of a trial of add-on therapy depends on the desired outcome. A trial of days to weeks may be sufficient for symptom relief, whilst it may take weeks to months for benefits to be seen in exacerbation rates. For most preventive therapies, improvements begin within days, but the full benefit may only be evident after 3 or 4 months, especially in severe and chronically under-treated disease [GINA, 2006].

Short-acting beta2-agonists may be needed on a regular basis to provide temporary relief of uncontrolled symptoms. The aim is to stop the need for reliever medication by using adequate preventive therapy.

Inhaled corticosteroids are usually prescribed at the lowest dose needed to achieve control.

Inhaled long-acting beta2-agonists: when starting therapy with these drugs, it may be more practical to prescribe separate inhalers to allow titration of doses, and separate inhalers make it easier to step down treatment if symptoms improve. However, a combination inhaler should be considered once the dose has been titrated as this will ensure that a long-acting beta2-agonist is not taken without an inhaled corticosteroid.

Leukotriene receptor antagonists may be preferred over modified-release theophylline because they have fewer adverse effects.

Oral corticosteroids (daily) are an option for children whose asthma remains inadequately controlled after step 4, but they should not be prescribed without specialist advice.

Omalizumab: is an option as add-on therapy to inhaled corticosteroids in children with moderate to severe asthma but this should only be prescribed on specialist advice. Omalizumab is a humanised monoclonal antibody manufactured by recombinant DNA technology. It is given by subcutaneous injection and is licensed for use in people aged over 6 years [ABPI Medicines Compendium, 2010]. It is a Black Triangle product subject to intensive monitoring by the Medicines and Healthcare products Regulatory Agency (MHRA).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

For steps 2, 3, and 4, the benefits of treatment in trials are based on improvements in symptoms and lung function, reduced exacerbations, and a good safety profile. The British Thoracic Society based their add-on regimens on extrapolated evidence from trials of add-on therapy to inhaled corticosteroids (ICS) and on previous guidelines. Few clinical trials in specific patient groups are available to guide management.

Inhaled corticosteroids (ICS): The evidence suggests that ICS are the most effective preventive treatment for all people with asthma. Nevertheless, there are concerns about local and systemic adverse effects when ICS are used in high doses. Clinical trials show no difference in efficacy (provided adherence is good) between giving inhaled corticosteroids and long-acting beta2-agonists in combination or in separate inhalers. In clinical practice, however, combination inhalers may improve compliance. Combination inhalers are therefore recommended by the National Institute for Health and Care Excellence [NICE, 2008] and the Medicines and Healthcare products Regulatory Agency [MHRA, 2008] as they:

Guarantee that the long-acting beta2-agonist is not taken without an inhaled corticosteroid.

Aid adherence.

Although there are no controlled trials, expert opinion in the British guideline on the management of asthma: a national clinical guideline is that children of all ages who are being treated at step 4 may benefit from a trial of ICS above the maximum recommended dose before moving to step 5, provided this is initiated by a specialist [SIGN and BTS, 2011].

Long-acting beta2-agonists (LABA): The evidence suggests that adding a LABA provides better asthma control than increasing ICS above 400 micrograms. In children the dose at which add-on therapy appears to be more beneficial is when ICS exceed 400 micrograms/day (beclometasone equivalent). Use of a LABA alone (without ICS) appears to be associated with increased risk of asthma-related death. Larger prospective studies are needed to confirm these findings.

Leukotriene receptor antagonists (LTRA): The evidence suggests that leukotriene receptor antagonists improve asthma symptoms and lung function when added to ICS, but they do not provide greater benefit than increasing ICS alone.

Theophylline: The evidence suggests that increasing the ICS dose provides better asthma control than adding in theophylline. Comparison studies with other add-on therapies are limited, but theophylline appears to have a worse adverse effect profile than other drugs.

Cromones: Limited and inconclusive evidence suggests that cromones may provide some benefit in controlling asthma symptoms.

Omalizumab: Use of omalizumab has been studied in children aged 5–12 years and has been shown to significantly reduce clinically significant exacerbations. Most children studied were taking long acting beta2-agonists or a leukotriene antagonist. Omalizumab should only be administered under direct medical supervision because of the risk of anaphylaxis which has been reported after the first dose and also after 1 year [SIGN and BTS, 2011].

Management in people over 12 years

People over 12 years of age with uncontrolled symptoms on current treatment: How do I manage?

Adjust treatment using the step-wise approach outlined below.

Before starting a new drug or stepping up treatment, confirm with the person their understanding of the role of treatment, adherence to treatment, inhaler technique, and appropriate elimination of trigger factors.

Choose an effective delivery device on the basis of convenience, cost, and suitability:

Step 1: Prescribe a short-acting beta2-agonist to all people with asthma, for rapid symptom relief.

Step 2: Consider starting an inhaled corticosteroid (ICS) at a dose most appropriate to the severity of symptoms (for beclometasone CFC-free as Clenil Modulite® this is 200 to 800 micrograms/day, with 400 micrograms/day being appropriate for most people older than 12 years). Use half the dose for Qvar®. Indications include:

Having symptoms three times weekly or more, or

Awakening with symptoms one night weekly or more, or

Having an exacerbation in the past 2 years, or

Using inhaled beta2-agonist three times weekly or more.

If ICS are not tolerated, consider starting a leukotriene receptor antagonist or cromone. Long-acting beta2-agonists (LABA) should only be prescribed with an ICS and therefore should not be considered an alternative to ICS.

Step 3: Consider starting a long-acting beta2-agonist (LABA) if symptoms are still uncontrolled with the ICS (irrespective of the dose used):

If the person has a good response to the LABA with adequate symptom control, continue the LABA and current dose of the ICS. Consider using a combination inhaler.

If the person has a good response to the LABA but control remains inadequate, continue the LABA, but increase ICS up to 800 micrograms/day (half the dose for Qvar®). If the person is receiving 800 micrograms/day and control remains poor, move to step 4.

If the person does not respond to LABA, stop LABA therapy and increase ICS up to 800 micrograms/day (unless the person is already receiving this dosage). If control remains poor, consider an alternative add-on treatment, such as a leukotriene receptor antagonist or modified-release theophylline, before moving to step 4.

The Symbicort SMART ® regimen (a budesonide/formoterol combination inhaler used as a preventer and reliever) is an alternative in selected adults (18 year of age and older) who respond to a LABA but are poorly controlled, or in adults who are taking an ICS alone (above 400 micrograms/day) but are poorly controlled. The regular maintenance dose of budesonide should not be decreased, and may be budesonide 200 or 400 micrograms twice a day, depending on symptom severity. If the person regularly uses Symbicort® as a reliever once a day or more, review treatment.

People using the Symbicort SMART® regimen should be advised to continue using the inhaler regularly twice a day, as well as when required. Careful explanation is needed about why Symbicort® can be used as a reliever as well as a preventer, and why it is important to arrange a review if Symbicort® regularly needs to be used as a reliever (to review control of asthma and the risk of dose-related adverse effects).

Step 4: If control is still inadequate, either increase ICS to the maximum dose (for beclometasone CFC-free as Clenil Modulite®, this is 2000 micrograms/day) or consider starting a fourth drug that the person is not already using, such as a leukotriene receptor antagonist, modified-release theophylline, or an oral modified-release beta2-agonist.

Step 5: Refer to a specialist in respiratory medicine. Consider stopping any add-on therapy (or reducing the ICS dose) if these options are ineffective, whilst referring to a specialist.

Offer self-management information, including written action plans focusing on the individual's needs.

Additional information

Additional information

The duration of a trial of add-on therapy depends on the desired outcome. A trial of days to weeks may suffice for symptom relief, whilst it may take weeks to months for benefit to be seen in exacerbation rates. For most preventive therapies, improvements begin within days, but the full benefit may only be evident after 3 or 4 months, especially in severe and chronically undertreated disease [GINA, 2006].

Short-acting beta2-agonists may be needed on a regular basis to provide temporary relief of uncontrolled symptoms. The aim is to stop the need for reliever medication by using adequate preventive therapy.

Inhaled corticosteroids are usually prescribed at the lowest dose needed to achieve control and are rarely not tolerated.

Inhaled long-acting beta2-agonists (LABA): when starting therapy with LABA, it may be more practical to prescribe separate LABA and ICS inhalers to allow titration of doses. However, a combination inhaler should be considered once the dose has been titrated as this will ensure that a long-acting beta2-agonist is not taken without an inhaled corticosteroid.

Leukotriene receptor antagonists may be preferred to modified-release theophylline or oral modified-release beta2-agonist because they are associated with fewer adverse effects. In practice modified-release theophylline and oral modified-release beta2-agonists are not routinely prescribed in primary care.

Oral corticosteroids are an option for people whose asthma remains inadequately controlled after step 4, but they should not be prescribed without specialist advice.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

For steps 2, 3, and 4, the benefits of treatment in trials are based on improvements in symptoms and lung function, reduced exacerbations and a good safety profile. The British Thoracic Society based their add-on regimens on extrapolated evidence from trials of add-on therapy to ICS and on previous guidelines. Few clinical trials are available in specific patient groups to guide specific management.

Inhaled corticosteroids (ICS): The evidence suggests that ICS are the most effective preventive treatment for all people with asthma. Nevertheless, there are concerns about local and systemic adverse effects when ICS are used in high doses.

Long-acting beta2-agonists (LABA): The evidence suggests that adding a LABA controls asthma better than increasing the ICS dose. Use of LABA alone (without ICS) appears to be associated with an increased risk of asthma-related death. Clinical trials show no difference in efficacy (provided adherence is good) between giving inhaled corticosteroids and long-acting beta2-agonists in combination or in separate inhalers. In clinical practice, however, combination inhalers may improve compliance. Combination inhalers are therefore recommended by the National Institute for Health and Care Excellence [NICE, 2008] and the Medicines and Healthcare products Regulatory Agency [MHRA, 2008] as they:

Guarantee that the long-acting beta2-agonist is not taken without an inhaled corticosteroid.

Aid adherence.

Leukotriene receptor antagonists: The evidence suggests that these agents improve asthma symptoms and lung function when added to ICS; however, they do not provide any greater benefit than increasing ICS alone.

Theophylline: The evidence suggests that increasing the ICS dose provides better asthma control than adding in theophylline. Comparison studies with other add-on therapy are limited, but theophylline appears to have a worse adverse effect profile than other drugs used.

Cromones: Limited and inconclusive evidence suggest that cromones may provide some benefit in controlling asthma symptoms.

Always refer people to a specialist before starting therapy with oral corticosteroids, as they require close monitoring for such adverse effects as hypertension, diabetes, reduced growth (in children), and cataracts.

Combination inhalers: evidence indicates that using the combination inhaler Symbicort® (budesonide and formoterol) as a maintenance and reliever therapy (Symbicort SMART®) may be similarly effective to conventional methods at reducing exacerbation rates in people with moderate to severe asthma.

Follow up

What follow up is needed in someone with asthma?

Review a person with stable asthma at least once a year. More frequent follow up may be needed after the initial diagnosis, for example reassess within 2–3 months, when there is a change to medication, or in people with severe asthma, poor lung function or recurrent exacerbations.

Consider monitoring people with poor lung function and with a history of exacerbations in the previous year more often.

When assessing asthma control:

Use specific (closed) questions, because broad non-specific questions may underestimate symptoms.

In adults, use a questionnaire such as The Royal College of Physicians 3 questions or the Asthma Control Questionnaire or Asthma Control Test.

In children, use a symptom score such as the Asthma Control Questionnaire or the Children's Asthma Control Test.

Ask about symptoms during the day; difficulty sleeping; and the impact of asthma on such activities as exercise, work, school, and psychological well-being in the past week or month.

Assess lung function using spirometry or peak expiratory flow rate and compare with the previously recorded value. Reduced lung function may indicate current bronchoconstriction or a long-term deterioration in lung function. Carry out a detailed assessment if there has been a reduction in lung function.

Update the best peak flow expiratory rate in adults every few years and more often in growing children.

Ask about past exacerbations and their frequency, and whether oral corticosteroids or hospital admission was needed.

Ask about possible trigger factors, such as exercise, work, and allergens.

Ask about other conditions that are known to co-exist with asthma and aggravate symptoms, for example, allergic rhinitis, sleep apnoea, and gastro-oesophageal reflux disease.

Look for signs of complications which may necessitate referral to a specialist.

In children, monitor growth (height and weight centile) annually.

Review asthma medication:

Ask about the use of reliever medication, any benefits seen with changes in medication, and adherence with treatment (which can be assessed by reviewing prescription refill frequency).

Assess inhaler technique. Reinforce the correct use of inhalers at each review. Ask the person to show you how they use their inhaler, and correct any problems by demonstrating the technique and having the person repeat it back to you. For more information on how to use inhalers (with demonstrations), see www.asthma.org.uk or www.ginasthma.org.

Ask about smoking habits in adults and adolescents, and in children ask about exposure to tobacco smoke. Encourage people with asthma or parents of children with asthma to stop smoking.

Review self-management information and make any necessary changes to written action plans.

Discuss future career choices with adolescents, and highlight occupations that might increase the risk of developing occupational asthma. These include forestry workers, chemical workers, plastics and rubber workers, metal workers, welders, textile workers, electrical and electronic production workers, storage workers, farm workers, waiters, cleaners, painters, dental workers, and laboratory technicians.

The Royal College of Physicians 3 questions

The Royal College of Physicians 3 questions

The 'Royal College of Physicians (RCP) 3 questions' is simple to use in every day clinical practice. Answering 'no' to all three questions is consistent with controlled asthma.

Table 1 . Royal College of Physicians' 'three questions' for assessing asthma control.
In the last week/month: Yes No
Have you had difficulty sleeping because of your asthma symptoms (including cough)? 1 0
Have you had your usual asthma symptoms during the day (e.g. cough, wheeze, chest tightness, or breathlessness)? 1 0
Has your asthma interfered with your usual activities (e.g. housework, work, school)? 1 0
3 questions score (0–3)
This score should be used only for people who are at least 16 years old and after the diagnosis of asthma has been established [Pearson and Bucknall, 1999; SIGN and BTS, 2011].

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

The aim of a structured review is to assess how well a person's asthma is controlled and to identify possible triggers of poor control. Then, if needed, treatment can be changed (stepped up, down or changed) to help optimize control and reduce exacerbations and hospitalizations.

Current control is the best predictor for future exacerbations. Expert opinion in the British guideline on the management of asthma: a national clinical guideline is that for a given level of symptoms people with poor lung function and a history of recent exacerbations may be at increased risk of future exacerbations [SIGN and BTS, 2011].

Asthma morbidity questionnaires: Questionnaires have been developed to standardize the assessment of asthma symptom control. Asking people about asthma symptoms and their effects on everyday life is important to improve asthma management [Rees, 2006].

Ask closed questions. Asking general questions such as 'how is your asthma today?' is likely to generate a non-specific reply. Closed questions are more likely to result in useful information [SIGN and BTS, 2011]. Expert opinion in the British guideline on the management of asthma: a national clinical guideline is that it is best to use a validated questionnaire [SIGN and BTS, 2011]. Monitoring peak expiratory flow rate in addition to monitoring symptoms has not been shown to improve asthma control with the possible exception of adults who have severe disease or who have a poor perception of bronchoconstriction.

The 'Royal College of Physicians 3 questions' has not been well validated in adults and has not been validated in children. However, its simplicity is attractive for clinical practice. The Quality and Outcomes Framework for GMS contract 2012/2013 also suggests use of this questionnaire as an effective way of assessing asthma symptoms [BMA and NHS Employers, 2012].

The Asthma Control Questionnaire has been well validated in adults and children aged over 5 years.

The Asthma Control Test has been validated in adults and children aged over 3 years.

Structured reviews: The evidence shows that people have fewer exacerbations, have improved symptoms, and miss less school or work if they undergo structured asthma reviews, especially if the assessments are done by trained professionals. Telephone consultations may be as effective as face-to-face consultations [Pinnock and Shah, 2007].

Assessing lung function: Reduced lung function compared to previously recorded values may indicate current bronchoconstriction or a long term decline in lung function and should prompt detailed assessment [SIGN and BTS, 2011]. Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that a personal best peak flow expiratory rate should be measured once treatment has been optimised and updated every few years in an adult and more frequently in a child [SIGN and BTS, 2011].

Inhaler technique: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that inhalers should only be prescribed after the person has received training in the use of the inhaler device and has demonstrated satisfactory technique [SIGN and BTS, 2011].

Comorbidities: Gastro-oesophageal reflux disease, allergic rhinitis, obesity, and obstructive sleep apnoea have been reported in greater proportions of people with difficult-to-treat asthma. It is important to recognize such conditions because they appear to aggravate asthma symptoms and need treatment. However, to date, no evidence indicates that treating these conditions improves asthma control [GINA, 2006; SIGN and BTS, 2011].

Smoking: Smoking may cause poor asthma control. Past smoking can be associated with poor control due to fixed airway obstruction, and current smoking reduces the effectiveness of inhaled and oral corticosteroids [GINA, 2006].

Monitoring growth in children: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends to monitor growth (height and weight centile) annually [SIGN and BTS, 2011].

Self management information: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that all people with asthma should be offered self-management education and should also have a personalised action plan [SIGN and BTS, 2011].

Discussing the risk of occupational asthma with adolescents: This recommendation and the occupations listed are based on expert opinion in the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Referral

When is a referral recommended in people with asthma?

The decision to refer is influenced by local referral pathways, the individual, and the experience of the primary healthcare provider.

In addition to respiratory physicians and paediatricians with a specialist interest in respiratory medicine, such specialists as dietitians, physiotherapists, occupational therapists, and respiratory nurse specialists may be involved in the management of asthma at any stage.

Admit or refer adults for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt:

Unexpected clinical findings (for example crackles, clubbing, cyanosis, cardiac disease).

Persistent non-variable breathlessness.

Monophonic, unilateral or fixed wheeze or stridor.

Persistent chest pain or atypical features.

Prominent systemic features (for example weight loss, myalgia, fever).

Persistent cough or sputum production.

Spirometric or peak expiratory flow measurements that do not fit the clinical picture, for example unexplained restrictive spirometry.

Suspected occupational asthma.

Non-resolving pneumonia.

Inadequate response to maximum guideline treatment.

Admit or refer children for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt (the younger the child, the more difficult it is to be sure that wheezing is due to asthma):

Unexpected clinical findings (for example abnormal voice, focal chest signs, dysphagia, inspiratory wheeze, stridor).

Symptoms present from birth, or perinatal lung problem.

Excessive vomiting or posseting.

Severe upper respiratory tract infection.

Persistent productive cough.

Family history of unusual chest disease.

Failure to thrive.

Parental anxiety.

Inadequate response to maximum guideline treatment, particularly if oral corticosteroids are needed frequently, or use of the maximum dose of inhaled corticosteroids.

The urgency of a referral to secondary care or admission to hospital should be appropriate to the clinical situation.

For indications of when to admit someone with an acute exacerbation of asthma, see When to admit to hospital in Scenario: Acute asthma exacerbation.

Additional tests in secondary care

Additional tests in secondary care

Other tests available in secondary care include:

Indirect testing for bronchoconstriction, for example more than 15% decrease in the forced expiratory value in 1 second after 6 minutes of running.

Testing for bronchial hyper-responsiveness using histamine or methacholine.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006b].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2011].

Scenario: Controlled asthma on current treatment

Scenario: Controlled asthma on current treatment

1months3060monthsBoth

Management of controlled asthma

Children and adults with controlled symptoms on current treatment: How do I manage?

Do NOT step down treatment for people who have ongoing symptoms or need inhaled short-acting beta2-agonists, and those who have had a recent exacerbation.

If a person has controlled symptoms, consider the following approach to step-down treatment:

Make sure the person feels that their asthma is controlled and that they are willing to try step-down treatment.

Reduce the dose of inhaled corticosteroids slowly. The usual protocol is to decrease the dose by 25% to 50% per 3-month visit. Explain the potential for worsening symptoms and the increased risk of an exacerbation.

Some children with milder asthma and a clear seasonal pattern to their symptoms may tolerate a more rapid dose reduction during their 'good' season.

Review the person on a regular basis; promote lifestyle advice, assess for worsening symptoms, and consider increasing medication if the person's asthma deteriorates.

If stepping down is not possible, and the person is stable on an inhaled corticosteroid and a long-acting beta2-agonist, consider prescribing a combination inhaler.

Discuss the reason for reducing medication (to minimize adverse effects), and always take the person's preference into consideration.

Update the person's written 'action plan' and reinforce how to recognize and manage an acute exacerbation.

Tailor the management to the individual, on the basis of their combination of drugs and the doses needed to achieve asthma control:

If a person is on a combination of inhaled corticosteroids (ICS) and add-on therapy, slowly reduce the ICS to the lowest dose possible; if asthma control is maintained consider stopping add-on therapy. Some experts (although there is no clear evidence to do so) recommend discontinuing any regular use of a beta–agonist (short or long–acting) before reducing the inhaled corticosteroid dose below 400 micrograms daily.

Preventive ICS treatment may possibly be stopped if asthma remains controlled on the lowest possible dose and symptoms do not recur for one year.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011] and guidelines from the Global Initiative for Asthma [GINA, 2006]:

The reduced need for medication once control is achieved is not fully understood. Possibilities include a reversal of long-term inflammation in the airways or spontaneous improvement as part of the cyclical natural history of asthma [GINA, 2006].

Few studies have investigated the most appropriate way of stepping down treatment. One study in adults with stable asthma who used at least 900 micrograms of inhaled corticosteroids daily showed that the dose could be halved every 3 months with no significant deterioration in symptoms [SIGN and BTS, 2011].

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006b].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2011].

Follow up

What follow up is needed in someone with asthma?

Review a person with stable asthma at least once a year. More frequent follow up may be needed after the initial diagnosis, for example reassess within 2–3 months, when there is a change to medication, or in people with severe asthma, poor lung function or recurrent exacerbations.

Some people may not wish to attend for regular review. A structured interview by telephone may be an alternative approach. Ideally, candidates should have stable asthma, and face-to-face contact should be encouraged at a later date to assess their inhaler technique.

Review asthma control:

When assessing asthma control use specific (closed) questions because broad non-specific questions may underestimate symptoms. Responses can be recorded easily and can form the basis of a symptom diary.

In adults, use a questionnaire such as The Royal College of Physicians 3 questions or the Asthma Control Questionnaire or Asthma Control Test.

In children, use a symptom score such as the Asthma Control Questionnaire or the Children's Asthma Control Test (pdf).

Ask about symptoms, during the day; difficulty sleeping; and the impact of asthma on such activities as exercise, work, or school in the past week or month.

Assess lung function using spirometry or peak expiratory flow rate and compare with the previously recorded value. Reduced lung function may indicate current bronchoconstriction or a long-term deterioration in lung function. Carry out a detailed assessment if there has been a reduction in lung function.

Update the best peak flow expiratory rate in adults every few years and more often in growing children.

Ask about past exacerbations and their frequency, and whether oral corticosteroids or hospital admission was needed.

Ask about possible trigger factors such as exercise, work, and allergens.

Ask about other conditions that are known to co-exist with asthma and aggravate symptoms, for example allergic rhinitis, sleep apnoea, and gastro-oesophageal reflux disease.

Look for signs of complications which may necessitate referral to a specialist.

In children, monitor growth (height and weight centile) annually.

Review asthma medication:

Ask about the use of reliever medication, any benefits seen with changes in medication, and adherence with treatment.

Assess inhaler technique. Reinforce the correct use of inhalers at each review. Ask the person to show you how they use their inhaler, and correct any problems by demonstrating the technique and having the person repeat it back to you. For more information on how to use inhalers (with demonstrations), see www.asthma.org.uk or www.ginasthma.org.

Ask about smoking habits in adults and adolescents, and in children ask about exposure to tobacco smoke. Encourage people with asthma or parents of children with asthma to stop smoking.

Review Self-management information and make any necessary changes to written action plans.

Discuss future career choices with adolescents, and highlight occupations that might increase the risk of developing occupational asthma. These include forestry workers, chemical workers, plastics and rubber workers, metal workers, welders, textile workers, electrical and electronic production workers, storage workers, farm workers, waiters, cleaners, painters, dental workers, and laboratory technicians.

The Royal College of Physicians 3 questions

The Royal College of Physicians 3 questions

The 'Royal College of Physicians (RCP) 3 questions' is simple to use in every day clinical practice. Answering 'no' to all three questions is consistent with controlled asthma.

Table 1 . Royal College of Physicians' 'three questions' for assessing asthma control.
In the last week/month: Yes No
Have you had difficulty sleeping because of your asthma symptoms (including cough)? 1 0
Have you had your usual asthma symptoms during the day (e.g. cough, wheeze, chest tightness, or breathlessness)? 1 0
Has your asthma interfered with your usual activities (e.g. housework, work, school)? 1 0
3 questions score (0–3)
This score should be used only for people who are at least 16 years old and after the diagnosis of asthma has been established [Pearson and Bucknall, 1999; SIGN and BTS, 2011].

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

The aim of a structured review is to assess how well a person's asthma is controlled and to identify possible triggers of poor control. Then, if needed, treatment can be changed (stepped up, down or changed) to help optimize control and reduce exacerbations and hospitalizations.

Current control is the best predictor for future exacerbations. Expert opinion in the British guideline on the management of asthma: a national clinical guideline is that, for a given level of symptoms, people with poor lung function and a history of recent exacerbations may be at increased risk of future exacerbations [SIGN and BTS, 2011].

Asthma morbidity questionnaires: Questionnaires have been developed to standardize the assessment of asthma symptom control. Asking people about asthma symptoms and their effects on everyday life is important to improve asthma management [Rees, 2006].

Ask closed questions. Asking general questions such as 'how is your asthma today?' is likely to generate a non-specific reply. Closed questions are more likely to result in useful information [SIGN and BTS, 2011]. Expert opinion in the British guideline on the management of asthma: a national clinical guideline is that it is best to use a validated questionnaire [SIGN and BTS, 2011]. Monitoring peak expiratory flow rate in addition to monitoring symptoms has not been shown to improve asthma control with the possible exception of adults who have severe disease or who have a poor perception of bronchoconstriction.

The 'Royal College of Physicians 3 questions' has not been well validated in adults and has not been validated in children. However, its simplicity is attractive for clinical practice. The Quality and Outcomes Framework for GMS contract 2012/2013 also suggests use of this questionnaire as an effective way of assessing asthma symptoms [BMA and NHS Employers, 2012].

The Asthma Control Questionnaire has been well validated in adults and children aged over 5 years.

The Asthma Control Test has been validated in adults and children aged over 3 years.

Structured reviews: The evidence shows that people have fewer exacerbations, have improved symptoms, and miss less school or work if they undergo structured asthma reviews, especially if the assessments are done by trained professionals. Telephone consultations may be as effective as face-to-face consultations [Pinnock and Shah, 2007].

Assessing lung function: Reduced lung function compared to previously recorded values may indicate current bronchoconstriction or a long term decline in lung function and should prompt detailed assessment [SIGN and BTS, 2011]. Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that a personal best peak flow expiratory rate should be measured once treatment has been optimised and updated every few years in an adult and more frequently in a child [SIGN and BTS, 2011].

Inhaler technique: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that inhalers should only be prescribed after the person has received training in the use of the inhaler device and has demonstrated satisfactory technique [SIGN and BTS, 2011].

Comorbidities: Gastro-oesophageal reflux disease, allergic rhinitis, obesity, and obstructive sleep apnoea have been reported in greater proportions of people with difficult-to-treat asthma. It is important to recognize such conditions because they appear to aggravate asthma symptoms and need treatment. However, to date, no evidence indicates that treating these conditions improves asthma control [GINA, 2006; SIGN and BTS, 2011].

Smoking: Smoking may cause poor asthma control. Past smoking can be associated with poor control due to fixed airway obstruction, and current smoking reduces the effectiveness of inhaled and oral corticosteroids [GINA, 2006].

Monitoring growth in children: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends to monitor growth (height and weight centile) annually [SIGN and BTS, 2011].

Self management information: Expert opinion in the British guideline on the management of asthma: a national clinical guideline recommends that all people with asthma should be offered self-management education and should also have a personalised action plan [SIGN and BTS, 2011].

Discussing the risk of occupational asthma with adolescents: This recommendation and the occupations listed are based on expert opinion in the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Scenario: Acute asthma exacerbation

Scenario: Acute asthma exacerbation

1months3060monthsBoth

Assessment

What assessment is recommended during an exacerbation of asthma?

Ask about possible trigger factors, such as a recent upper respiratory tract infection.

Ask about the type and duration of symptoms, what treatment has been started (if any), and whether treatment has improved symptoms.

Assess the severity of the exacerbation:

Look for signs of exhaustion (inability to complete sentences) and cyanosis (bluish lips or extremities).

Examine the person's chest and record the respiratory rate, pulse, and blood pressure.

Record the peak expiratory flow rate (if the person is old enough to comply) and use the best of three recordings to grade the severity of the attack on the basis of the person's best or predicted value:

Moderate: more than 50–75%.

Acute severe: 33–50%.

Life-threatening: < 33%.

Measure a person's oxygen saturation in room air using pulse oximetry (if available).

Ask about depression, alcohol misuse, poor compliance with medication, social isolation and any previous exacerbations. Together with the severity of the exacerbation, this will help to determine the risk of death and the need for hospital admission.

Additional information

Additional information

Symptoms are a more sensitive measure than peak expiratory flow rate (PEFR) of the onset of an exacerbation, as the increase in symptoms usually precedes the deterioration in PEFR. Symptoms vary among individuals and age ranges. No symptom or sign alone (or together) is specific, and their absence does not exclude a severe exacerbation.

Signs to look for and record include:

Pulse rate (increasing suggests worsening asthma, whilst a decrease indicates a life-threatening situation).

Respiratory rate and use of accessory muscles.

Degree of wheeze (less apparent with increasing obstruction).

Degree of agitation and consciousness.

Peak expiratory flow rate is a more reliable indicator of severity than symptoms. Use a predicted PEFR value only if the person's recent (within 2 years) best PEFR is unknown. Ideally, use the person's own peak flow meter or a similar type.

Pulse oximetry may not be available in primary care, especially for young children.

When deciding to admit someone to hospital, assess the severity of this current exacerbation and also review the person's history. If they have any associated medical, behavioural, or psychosocial factors that are of concern, lower the threshold for admission.

Use the criteria in Table 1 to grade and record the severity of an asthma exacerbation.

Table 1 . Levels of severity of acute asthma exacerbation.
Level of severity Criteria
Near-fatal Respiratory acidosis (increased arterial carbon dioxide) and/or requiring mechanical ventilation with increased inflation pressures
Life-threatening Any one of the following in someone with severe asthma:
Peak expiratory flow rate < 33% of best or predicted Oxygen saturation < 92% Silent chest Cyanosis Feeble respiratory effort Bradycardia Dysrhythmia Hypotension Exhaustion Confusion Coma
Acute severe Any one of: Peak expiratory flow rate 33–50% of best or predicted Respiration rate: 2–5 years old: 40 breaths/min 5–12 years old: 30 breaths/min > 12 years old: 25 breaths/min Pulse: 2–5 years old: 140 beats/min 5–12 years old: 125 beats/min > 12 years old: 110 beats/min Inability to complete sentences in one breath Use of accessory neck muscles (in children)
Moderate asthma exacerbation Increasing symptoms Peak expiratory flow rate > 50–70% of best or predicted No features of acute severe asthma
Brittle asthma Type 1: wide variability in peak expiratory flow rate despite intensive therapy (i.e. > 40% diurnal variation for > 50% of the time over > 150 days) Type 2: sudden severe attacks despite apparently well-controlled asthma
Caution: people with severe or life-threatening attacks sometimes do not appear to be distressed and may not have all the features listed. Agitation and behavioural changes in a child may be a sign of hypoxia. Consider the occurrence of any feature as an alert for the presence of severe or life-threatening asthma [SIGN and BTS, 2011].

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Trigger factors: the evidence from small case-controlled studies shows that sensitization and exposure to allergens (house dust mites, cats, dogs) and respiratory viruses are independently and synergistically associated with asthma exacerbations [Green et al, 2002]. The role of atypical bacteria is much less certain [GINA, 2006].

Symptoms: early intervention (via an action plan) at signs of a possible exacerbation is essential, as most (88–92%) asthma attacks severe enough to require hospital admission develop relatively slowly, over 6 hours or more. In one study, more than 80% developed over 48 hours [SIGN and BTS, 2011].

Peak expiratory flow rate improves recognition of asthma severity and helps with decisions about management at home or in hospital. The most clinically useful value is peak expiratory flow rate measured as a percentage of the person's best [SIGN and BTS, 2011].

Pulse oximetry can help diagnose life-threatening asthma if a person's saturation is below 92%. A prospective study (n = 1184) of children aged 2–17 years suggested that low oxygen saturation predicts hospital admission, but no specific cut-off value is sufficiently accurate for clinical decision making [Keahey et al, 2002].

When to admit to hospital

When is hospital admission required?

Admit all people with a life-threatening asthma exacerbation (peak expiratory flow rate [PEFR] usually < 33% best or predicted and/or oxygen saturation < 92%).

Admit people with a severe asthma exacerbation (PEFR usually 33–50% best or predicted) who do not rapidly respond to initial treatment or who have a factor that warrants a lower threshold for admission.

Admit people with a moderate asthma exacerbation (PEFR usually > 50% best or predicted) who have a factor that warrants a lower threshold for admission.

The following factors should lower the threshold for admission:

People under 18 years.

Poor concordance.

Person lives alone.

Psychological problems such as depression, and alcohol or drug misuse.

Physical or learning disability.

Previous near-fatal attack or brittle asthma.

Persistent exacerbation despite an adequate dose of oral corticosteroids before presentation.

Presentation at night or in the afternoon.

Pregnancy.

Additional information

Additional information

Some people with a moderate to severe exacerbation (and no risk factors for a lower threshold of admission) may be managed in primary care only if they show a good response to initial treatment. The primary healthcare professional needs to make that decision on an individual basis. Their decision should be based on the knowledge of the person and how quickly they respond to initial treatment. If the healthcare professional has any doubt, does not have the appropriate facilities to assess and monitor treatment response, or cannot safely follow up the individual, admission to hospital is needed for further assessment.

Determine whether a person is at further risk of deterioration or death by assessing their medical, behavioural, and psychosocial history. See Table 1.

Table 1 . Important factors in near-fatal or fatal asthma exacerbation.
Medical risk factors Behavioural or psychosocial risk factors
Previous near-fatal episode of asthma (i.e. previous ventilation or respiratory acidosis) Non-compliance with treatment or monitoring
Previous hospital admission for asthma, especially within the past year Failure to attend appointments, or previous self-discharge from hospital
Requires three or more classes of asthma medication Psychiatric illness or learning difficulties, denial
Heavy use of beta2-agonist Misuse of alcohol or drugs
Repeated attendance at accident and emergency unit for asthma, especially within the past year Current or recent major tranquillizer use
'Brittle' asthma Income or employment problems, social isolation
Severe domestic, marital, or legal stress, child abuse
Obesity
Data from: [SIGN and BTS, 2011]

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Case-controlled studies have shown that people who die of asthma attacks or have near-fatal attacks are more likely to have associated adverse behavioural or psychological features. Deaths were also related to inadequate use of oral corticosteroids and poor follow up.

People who die of asthma are also likely to have had severe disease, poor compliance with medication, a hospital admission or visit to an accident and emergency department for asthma in the previous year, or a previous near-fatal attack.

An oxygen saturation (SpO2) of less than 92% is associated with a risk of hypercapnoea, which is a feature of life-threatening asthma. Hypercapnoea can only be detected by arterial blood gas measurement, not by pulse oximetry.

Managing people needing admission

Children and adults who need admission to hospital: How do I manage?

Organize urgent hospital admission.

Give high-flow oxygen (40–60%) with a tight-fitting mask. If pulse oximetry is available, adjust the flow rate to maintain an oxygen saturation of 94–98%.

Give a short-acting inhaled beta2-agonist:

For life-threatening asthma, give via a nebulizer, if available. Repeat every 20–30 minutes according to clinical response.

Ideally, nebulizers should be oxygen driven (flow rate of 6 L/min usually needed) to avoid worsening hypoxia.

For severe attacks, give via a nebulizer (preferred for children if available) or use a pressurized metered-dose inhaler with a large-volume spacer.

For an adult, give 4 puffs initially, followed by 2 puffs every 2 minutes according to response, up to 10 puffs.

For a child, give 2 puffs every 2 minutes according to response, up to 10 puffs.

Each puff should be given one at a time and inhaled with five tidal breaths.

The above process may be repeated every 10-20 minutes if clinically necessary; while the person is awaiting hospital admission.

For moderate attacks, use a pressurized metered-dose inhaler with a large-volume spacer.

Give the first dose of a course of prednisolone.

Monitor peak expiratory flow rate (if the person can comply) and oxygen saturation (if available) to assess response to treatment.

If the person does not respond to a beta2-agonist, consider continuous nebulized beta2-agonists or addition of ipratropium bromide (via a nebulizer). However, aim to get the person to hospital urgently.

Additional information

Additional information

High-flow oxygen: there is very little risk of causing high carbon dioxide retention with high-flow oxygen in people with asthma (unlike chronic obstructive pulmonary disease). Aim to keep the person's oxygen saturation between 94% and 98% (measured by pulse oximetry) by giving 6 L/min or a 40–60% flow rate whilst en route to hospital.

Inhaled short-acting beta2-agonist:

In life-threatening asthma, the agent should be delivered ideally by a high-flow oxygen-driven nebulizer. If an oxygen-driven nebulizer is unavailable, deliver by air-driven nebulizer (although be alert that oxygen desaturation may occur). Continuous nebulization is preferred in severe obstruction, but not all nebulizer systems can do this.

In severe asthma, the agent should be delivered by high-flow oxygen-driven nebulizer (preferred for children) or pressurized metered-dose inhaler with a large-volume spacer. If multiple puffs are needed, they should be given as single puffs into the spacer and inhaled with five tidal breaths after each, repeating until the prescribed number of puffs has been given. A short pause between puffs may be necessary to avoid hyperventilation.

In moderate asthma, the agent should be delivered by pressurized metered-dose inhaler with a large volume spacer.

Oral corticosteroids should be given as soon as possible. Oral administration is as effective as the intravenous route, provided that medication can be swallowed. If medication cannot be swallowed, consider intramuscular methylprednisolone 160 mg as an alternative to a course of oral prednisolone.

Table 1 . Doses of nebulized bronchodilators used in acute severe exacerbation of asthma.
Drug 2–5 years old 6–12 years old (higher dose for more severe) > 12 years old
Salbutamol 2.5 mg 2.5–5 mg 5 mg
Terbutaline 5 mg 5–10 mg 10 mg
Ipratropium (every 4 to 6 hours) 250 micrograms 250 micrograms 500 micrograms
When using intermittent nebulization, repeat beta2-agonist administration every 10–20 minutes. When using a continuous nebulizer, give the tabulated doses of beta2-agonist over 30–60 minutes [SIGN and BTS, 2011].

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline. Because most of the studies were small, had diverse designs, and involved people in secondary care settings, it is difficult to generalize findings to primary care [SIGN and BTS, 2011]:

If a person does not respond to initial treatment, the main aim is to get the person to hospital urgently for further support, such as intravenous medication and possibly ventilation.

Oxygen: people with a severe asthma attack are hypoxaemic; this should be corrected urgently with high-flow oxygen. Limited evidence (one randomized controlled trial, n = 74 adults) shows that 100% oxygen may worsen carbon dioxide retention, and improve peak expiratory flow rate to a lesser extent, compared with 28% oxygen [Rodolfo et al, 2005].

Inhaled beta2-agonists quickly correct bronchospasm with very few adverse effects. The evidence suggests salbutamol and terbutaline do not differ in efficacy. Delivery via a pressurized metered-dosed inhaler with a large-volume spacer appears to be as effective as delivery via a nebulizer. Continuous nebulization is at least as effective as bolus nebulization in relieving acute asthma. However, continuous nebulization appears to be more effective than bolus nebulization in asthma that is severe or unresponsive to treatment [SIGN and BTS, 2011].

Inhaled ipratropium bromide: the evidence suggests that combining nebulized ipratropium bromide with nebulized beta2-agonists in an acute attack may lead to a faster recovery and shorter duration of admission [SIGN and BTS, 2011].

Managing people not needing admission

Children and adults not needing admission to hospital: How do I manage?

Prescribe a short course of oral prednisolone (see Table 1 for doses). The usual dose for someone not taking a regular corticosteroid is:

Child < 2 years: 10 mg once a day for 3 days

Child 2–5 years: 20 mg once a day for 3 days

Child 6–12 years: 30–40 mg once a day for 3 days

Adult or child > 12 years: 40–50 mg once a day for 5 days

Do not prescribe antibiotics routinely, unless symptoms and signs suggest a bacterial infection.

Advise the person (or parent of a child) to use their short-acting beta2-agonist via a large-volume spacer.

For an adult, give 4 puffs initially, followed by 2 puffs every 2 minutes according to response, up to 10 puffs.

For a child, give 2 puffs every 2 minutes according to response, up to 10 puffs.

Each puff should be given one at a time and inhaled with five tidal breaths. Repeat every 10–20 minutes according to clinical response.

After the short-acting beta2-agonist has been given (up to 10 puffs), advise the person (or parent of a child):

To return to using their short-acting beta2-agonist as-required, up to four times a day (not exceeding 4-hourly use).

To monitor their peak expiratory flow rate (PEFR) and symptoms. If symptoms worsen, or PEFR decreases after starting treatment, they should seek further medical advice.

Consider initiating montelukast in children aged over 2 years with mild asthma early after the onset of symptoms.

Follow up a person (ideally) within 24 hours, or sooner if they deteriorate, and within 1 week after an exacerbation.

Additional information

Additional information

People whose condition deteriorates despite treatment normally need admission to hospital. Ideally, all people should be followed up after an exacerbation by telephone or, preferably, in person.

Inhaled beta2-agonists can be used on a regular basis to alleviate persistent symptoms during an exacerbation. Many people may have already implemented this procedure as part of their action plan.

Oral corticosteroids should be given for at least 5 days in adults, whilst 3 days is usually sufficient for children. Nevertheless, the length of a course should be tailored to the number of days necessary to bring about recovery. The benefits of corticosteroids can occur within 3–4 hours, and most people do not need tapering of the dose at the end of such a short course.

The dose of inhaled corticosteroids (ICS) does not need to be increased during an exacerbation, and people should remain on their usual dose. Treatment with ICS should not be used as an alternative to oral corticosteroids.

Antibiotics: explain to the individual that most exacerbations of asthma are not caused by a bacterial infection and antibiotics will not hasten recovery. If a person has a productive cough and elevated body temperature, consider an alternative diagnosis — see Differential diagnosis in adults and Differential diagnosis in children.

Table 1 . Dose of oral prednisolone used in acute severe exacerbation of asthma.
Dose of oral prednisolone (once daily) < 2 years old 2–5 years old 6–12 years old > 12 years old
People not taking regular oral corticosteroid 10 mg 20 mg 30–40 mg 40–50 mg*
People taking regular oral corticosteroid 2 mg/kg (maximum 40 mg) 2 mg/kg (maximum 60 mg) 2 mg/kg (maximum 60 mg) 2 mg/kg (maximum 60 mg)
* In practice, many healthcare professionals prescribe 30 mg/day. Data from: [BNF 53, 2007; BNF for Children, 2007; SIGN and BTS, 2011]

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Oral corticosteroids: the evidence shows that oral corticosteroids reduce mortality, relapse, subsequent hospital admission, and requirement for beta2-agonist therapy. The earlier oral corticosteroids are given in an acute attack, the better the outcome. Larger doses than those stated in the recommendation do not appear to provide any additional benefit.

Inhaled corticosteroids: no evidence indicates that doubling the dose of inhaled corticosteroids is effective in treating acute symptoms of asthma [SIGN and BTS, 2011].

Antibiotics: the evidence suggests that when an infection precipitates an exacerbation of asthma, it is likely to be viral. The role of bacterial infections has been overestimated [SIGN and BTS, 2011].

Montelukast: An update to the British Guideline on the Management of Asthma: a national clinical guideline states that there is evidence that initiating oral montelukast early after the onset of acute asthma in children aged over 2 years can result in decreased asthma symptoms and less need for subsequent healthcare attendances. There is no clear evidence to support the use of oral montelukast in moderate or severe asthma, but only in mild asthma [SIGN and BTS, 2011].

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006b].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2011].

Follow up

What follow up is recommended after an exacerbation of asthma?

Some people may not need follow up during a mild exacerbation. However, if there are signs of deterioration, review is necessary to determine whether admission to hospital is appropriate.

Sometimes attending for follow up may be impractical. Consider a telephone consultation to review the person early, and schedule a clinic consultation for a later date to assess inhaler technique and perform an examination.

People who have been discharged from hospital or from an emergency department should be followed up:

In primary care within 2 days of discharge.

By a respiratory specialist in about 1 month.

Assess the exacerbation:

Ask about the duration and severity of the exacerbation compared with any previous episodes. Record the number of exacerbations and hospital admissions.

Identify possible trigger factors, such as exercise, work, or allergens.

Optimize treatment:

Ask about compliance with treatment before the exacerbation and review the person's inhaler technique.

Provide advice on lifestyle, vaccinations, diet, exercise, and smoking. If the person or parent of the child smokes, advise them to stop.

Consider stepping-up treatment by increasing inhaled corticosteroids or adding in new preventive therapy.

Review self-management education and written action plan:

Review the person's understanding of how to recognize an exacerbation and what to do at the early signs of an exacerbation (increase beta2-agonist and start oral corticosteroids).

Reinforce understanding by updating the written action plan.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]. Many follow up studies have involved small numbers of people, mainly in a secondary care setting, and follow up was done by specialists using different methods. Evidence is scant on following up people who have not been admitted to hospital.

Follow up is necessary after an exacerbation, as the evidence suggests that more than 15% of people will have a relapse within 2 weeks [SIGN and BTS, 2011]. The follow up process should aim to identify a possible cause of the exacerbation so that strategies to prevent further exacerbations can be developed.

Follow up after discharge from hospital and emergency departments: this recommendation is based on expert opinion in the British Guideline on the Management of Asthma: a national clinical guideline which recommends that if the person requires admission for an exacerbation of asthma then the person's primary care practice should be informed within 24 hours of discharge from hospital, preferably by fax or e-mail to the person responsible for asthma care within the practice. They also recommend that the person should be assessed by either a respiratory physician or a hospital specialist asthma nurse about 1 month after admission [SIGN and BTS, 2011].

The evidence suggests that follow up after an exacerbation which involves providing self-management education and a written action plan may reduce hospital re-admissions and improve symptom control and self-management of asthma. Outcomes appear to differ little by the place or personnel involved [Bernard-Bonnin et al, 1995; Nathan et al, 2006].

Scenario: Management of exercise-induced asthma

Scenario: Management of exercise-induced asthma

1months3060monthsBoth

Managing exercise-induced asthma

Exercise-induced asthma: How do I manage?

If exercise-induced asthma is a symptom of poor asthma control, manage it as uncontrolled asthma.

If a person has otherwise well-controlled asthma, but finds exercise-induced asthma to be a problem:

Advise short-burst activities, exercising in humid environments, and breathing through the nose to avoid hyperventilation.

Prescribe use of a short-acting beta2-agonist 10–15 minutes before the start of exercise and after 2 hours of prolonged exercise, or after exercise has finished.

If exercise-induced symptoms persist despite use of a short-acting beta2-agonist (adequate dosage with good concordance):

Consider starting an inhaled corticosteroid.

If the individual is still symptomatic despite using an inhaled corticosteroid, consider prescribing a long-acting beta2-agonist or leukotriene receptor antagonist for regular use.

Other options, such as theophylline, sodium cromoglicate, or nedocromil sodium, and oral modified-release beta2-agonist (adults only) can be used but are less effective in exercise-induced asthma.

If the person does not respond to treatment and exercise-induced asthma is still problematic (especially in athletes), consider referral to a respiratory specialist.

Confirming the diagnosis of exercise-induced asthma can be difficult:

Ask about a cough (usually starting 6–10 minutes after the start of exercise) and associated chest tightness (up to 1–2 hours afterwards). Some people may have symptoms starting after exercise.

Ask about other symptoms not related to exercise, such as nocturnal cough, wheeze, or breathlessness, that might indicate poorly controlled asthma.

Give the person a peak flow diary and ask them to measure their peak flow before and 5 minutes after exercise to help support the diagnosis.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Very little evidence supports the use of any medication in exercise-induced asthma in children younger than 5 years. Most of the evidence is from poor quality trials involving small numbers of people with or without poorly controlled asthma, and using different doses of medication over different durations.

Exercise-induced asthma is often an indication of poorly controlled asthma. If control of asthma is improved, the symptoms of exercise-induced asthma will usually cease.

Inhaled short-acting beta2-agonists are the most effective therapy for prevention of exercise-induced asthma. Regular use offers no advantage over as-required regimens, and may result in tolerance [SIGN and BTS, 2011].

Long-acting beta2-agonists, leukotriene receptor antagonists, and cromones are more effective than placebo in controlling exercise-induced asthma in small randomized controlled trials, but they are no more effective than short-acting beta2-agonists [SIGN and BTS, 2011].

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006b].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2010].

Scenario: Suspected occupational asthma

Scenario: Suspected occupational asthma

144months3060monthsBoth

Managing occupational asthma

Suspected occupational asthma: How do I manage?

Refer any individual with suspected occupational asthma to a respiratory specialist for confirmation.

Suspect occupational asthma in adults who developed asthma in adulthood or have a recurrence of childhood asthma and have:

Asthma symptoms that are better on days away from work or on holidays.

A high-risk occupation, such as paint sprayers, bakers and pastry makers, nurses, chemical workers, animal handlers, welders, food processing workers, and timber workers.

Ask the person to keep a peak flow diary, recording their peak flow at work and away from work to show the specialist.

Additional information

Additional information

Work-aggravated asthma occurs when pre-existing asthma is aggravated by non-specific dust or fumes at work. In contrast, occupational asthma is pre-existing asthma which becomes additionally sensitized to an occupational agent.

Refer people with suspected occupational asthma to the occupational health service at the workplace (if available) or a respiratory specialist.

Occupational asthma is diagnosed in secondary care when all the following are true:

The diagnosis of asthma is confirmed.

A relationship between asthma and work exposures is confirmed, for example, by:

Serial measurements of peak expiratory flow rate at home and at work (at least three series of consecutive days at work with three periods away from work, at least four evenly spaced readings per day, and at least 3 days in each consecutive work period).

Specific and non-specific bronchial provocation tests.

A specific cause is identified.

Following confirmation, the person should relocate away from exposure as soon as possible, and ideally within 12 months of the first work-related symptoms of asthma. Sometimes, substitution of the hazard may be an alternative option.

Children may be affected by occupational allergens brought home by their parents.

More information and a computer tool for analysing data are available from www.occupationalasthma.com.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

The aim of management is to identify the cause, to remove the worker from exposure, and for the person to have worthwhile employment. Early identification and avoidance of the exposure offers the best chance of complete recovery. Studies have shown that the prognosis is worse for people who remain exposed after 1 year of symptoms compared with those removed earlier.

History: asking about symptoms improving away from work is more sensitive than asking about worsening symptoms at work, as many symptoms deteriorate in the hours after work or during sleep. However, these questions are not specific for occupational asthma and also identify people with asthma due to agents at home (who may improve on holidays) and those who do much less physical activity away from work.

Investigations: serial peak flow measurements are the most sensitive and specific initial investigation. Lung function tests away from work may have false-negative results. Specific bronchial provocation testing is the gold standard, but few facilities in the UK do such testing. Most cases of occupational asthma can be diagnosed in secondary care without such a test.

Lifestyle advice

Lifestyle advice

Self-management information

What information is needed in self-management education and action plans?

Give all people with asthma self-management education and a written action plan.

At each review, repeat education and advise on:

Taking medication and avoiding known trigger factors.

Recognizing poor asthma control (worsening symptoms or peak flow readings) and early signs of an exacerbation (sudden persistent worsening symptoms).

Presenting for follow up annually or more frequently if symptoms are not controlled.

A typical asthma action plan should include:

When to increase treatment (as defined by symptoms or peak expiratory flow rate).

How to change treatment in case of deterioration and when to go back to maintenance medication.

When to seek medical help.

Additional information

Additional information

Tailor self-management education and written action plans to the needs of the individual. Such plans may be particularly helpful in some high-risk people with a history of insidious deterioration of asthma, poor perception of deteriorating breathing, and poor adherence to medication, and in people with frequent exacerbations. Provide such people with a 'crash course' of oral corticosteroids and instructions, preferably in writing, on when to start treatment:

Advise people that poor asthma control may be suggested by:

Worsening symptoms (cough, wheeze, breathlessness), especially at night or during exercise.

Worsening peak expiratory flow rate (PEFR) compared with previous readings.

Advise people with worsening symptoms for a couple of days or a decrease in PEFR to initiate their personalized action plan. This plan should be based on the person's current medication, history, and severity of an exacerbation. Consider the following approach:

If a person's PEFR is > 75% (best or predicted), advise regular use of a short-acting beta2-agonist for 1–2 days until symptoms improve. If there is no benefit, start a course of oral prednisolone.

If a person's PEFR is 50–75% (best or predicted), advise starting a course of oral prednisolone with regular use of their short-acting beta2-agonist. If no benefit is seen after 1–2 days, seek medical help.

If a person's PEFR is < 50%, advise starting a course of oral prednisolone along with regular use of their short-acting beta2-agonist and seek medical help.

Examples of asthma action plans are available online from the National Asthma Campaign (www.asthma.org.uk).

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Studies vary widely in populations, setting, and disease severity. One approach cannot be assumed to be successful in all circumstances. Less evidence is available from primary care settings, and results are less consistent. Overall, self-management education packages appear to be effective, but no one individual component is consistently shown to be effective in isolation. A consistent finding in many studies has been improvements in people's self efficacy, knowledge, and confidence [SIGN and BTS, 2011].

Increasing low-dose inhaled corticosteroids (ICS) by as much as fourfold at the beginning of an exacerbation may be suitable for some people on low doses of maintenance ICS, but doubling ICS during an exacerbation has not been shown to provide benefit and is no longer recommended [SIGN and BTS, 2011].

Smoking

Smoking: What advice should I give someone with asthma?

Advise smokers with asthma to stop smoking and provide them with the appropriate help. For more information, see the CKS topic on Smoking cessation.

Advise people with asthma to, as far as possible, avoid exposure to tobacco smoke. For parents who smoke and have a child with asthma, this means either stopping smoking (the best option), or not smoking in the same room as the child (or, preferably, not smoking in the house).

Parents and parents-to-be who smoke should be advised about the many adverse effects of smoking on themselves and their children. They should be offered appropriate support to stop smoking.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

The evidence suggests that exposure to tobacco smoke in the home contributes to increased wheezing in infancy, increased risk of persistent asthma, increased severity of childhood asthma, and that starting smoking as a teenager increases the risk that asthma will persist. Active smoking in asthma results in worsening symptoms and decline in lung function, and it may inhibit the short-term response to inhaled or oral corticosteroids (although the mechanism of this effect is not certain) [Thomson et al, 2004].

Vaccinations

Vaccinations: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma that an influenza and a pneumococcal vaccination is advisable if asthma is severe and requires hospital admission or frequent use of corticosteroids.

Influenza vaccination is recommended for all people older than 6 months who have required hospital admission for an exacerbation of asthma, or who need continuous or frequently repeated use of inhaled or oral corticosteroids. For more information, see the CKS topic on Immunizations - seasonal influenza.

Pneumococcal vaccination is recommended in the following groups:

People (of any age) whose asthma is so severe that they require continuous or frequent repeated use of oral corticosteroids (i.e. at a dose equivalent to 20 mg or more of prednisolone daily).

Children weighing less than 20 kg, a dose prednisolone of 1 mg or more per kilogram body weight per day, for more than a month.

Note that pneumococcal vaccine is now part of the childhood immunization programme — see www.dh.gov.uk. For more information, see the CKS topic on Immunizations - pneumococcal.

Basis for recommendation

Basis for recommendation

These recommendations are based on government policy as discussed in the 'Green Book', published by the Department of Health [DH, 2006b].

A yearly influenza vaccination does not appear to protect people from exacerbations or improve asthma control [GINA, 2006].

Allergen avoidance

Allergen avoidance: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to avoid (if possible) known trigger factors, especially at times when asthma is poorly controlled.

Advise all adults to report promptly any worsening asthma control during work.

The person with asthma should identify trigger factors, where possible, by noting worsening symptoms or decreasing peak expiratory flow rates (PEFR) during exposure to certain situations. Some triggers cannot be avoided (for example air pollution, weather, viral illness), but at times of poor asthma control, it is prudent to do so if possible. Uncontrolled asthma is more sensitive to possible trigger factors.

Dust mites: sensitization to house dust mite is an important risk factor for the development of asthma, however in the absence of benefit from domestic aeroallergen avoidance, it is not possible to recommend it as a strategy for preventing childhood asthma. Overall, measures to decrease house dust mites have not been shown to have an effect on asthma severity. If a household member shows evidence of house dust mite allergy and wishes to try mite avoidance, strategies include complete barrier bed-covering systems, ensuring that susceptible children do not sleep in a lower bunk bed, removal of carpets or soft toys from beds, high-temperature washing of bed linen, application of acaricides (chemical agents that kill mites) to soft furnishings, and good ventilation.

Animal allergens, particularly cat and dog allergens, are potent inducers of asthma symptoms. Many experts recommend the removal of pets from the home of allergic people with asthma, but the reported effects are inconsistent.

Food and food additives (for example sulphites found in wine, beer, processed potatoes, shrimps) as an exacerbating factor for asthma are uncommon and occur primarily in young children. Do not recommend food avoidance unless there is a proven allergy, and then only with the supervision of a dietitian, especially in children.

Air pollutants (ozone, nitrogen oxide, acidic aerosols) and occasional weather changes have been associated with asthma symptoms and exacerbations, although there is no evidence to support a link between exposure to air pollutants and the induction of allergy. There is no need to recommend avoidance in people with stable asthma. Advise people with poorly controlled asthma who are troubled by outdoor triggers to minimize exposure, such as by not doing strenuous exercise or smoking in cold weather, low humidity, or times of high air pollution.

An occupational trigger will usually worsen asthma at work, and improvements will occur when the person is away from the work environment. Identify people with occupational triggers early and refer them to a respiratory specialist.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Allergen avoidance: the evidence that reducing allergen exposure can reduce morbidity and mortality is tenuous. In uncontrolled studies, children and adults have shown some benefit from exposure to very-low-allergen environments. However, the benefits cannot be necessarily attributed to allergen avoidance. Larger, well-designed studies of combined-allergen avoidance strategies in different groups are needed [GINA, 2006; SIGN and BTS, 2011].

Weight reduction, diet and exercise

Weight reduction, diet, and exercise: What advice should I give someone with asthma?

Advise overweight people that a healthy diet and regular exercise will help with weight reduction and improve asthma control:

Advise people (if possible) to take 30 minutes of exercise to increase their heart rate at least five times weekly. For more information on weight loss, see the CKS topic on Obesity.

Exercise — no specific exercise regimen can be recommended apart from that needed to adopt a healthier lifestyle (30 minutes of exercise to increase heart rate at least five times weekly). Advise people about precautions against exercise-induced asthma. See Scenario: Management of exercise-induced asthma.

Diet — no specific dietary recommendation can be given to people with asthma apart from a balanced diet, or a low-fat diet for people needing to lose weight. Observational studies in both adults and children have consistently shown that a high intake of fresh fruit and vegetables is associated with less asthma and better lung function. No intervention studies have yet been reported.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Weight reduction, diet, and exercise: the evidence is limited and based on small numbers of people with asthma. Weight reduction appears to improve asthma control, lung function, and symptoms in obese people. However, no convincing trial evidence shows that any specific diet or specific exercise regimen improves asthma control or symptoms [GINA, 2006; SIGN and BTS, 2011].

Comorbidities

Comorbidities: What advice should I give someone with asthma?

Advise all people with asthma and parents looking after children with asthma to report symptoms of conditions that could worsen asthma, such as rhinitis, sinusitis, gastro-oesophageal reflux disease, and sleep apnoea.

Explain that such symptoms as facial pain, nasal symptoms, indigestion, and snoring suggest co-existing conditions that may worsen asthma and need treatment.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011]:

Associated conditions, such as sinusitis, rhinitis, and gastro-oesophageal reflux disease, worsen asthma control. However, there is no conclusive evidence that managing these conditions results in significant clinical improvements in asthma symptoms.

Driving

Driving: What advice should I give someone with asthma?

For both group 1 (car or motorcycle) or group 2 (lorry or bus) entitlement:

The Driver and Vehicle Licensing Agency (DVLA) need not been informed unless attacks are associated with disabling giddiness, fainting, or loss of consciousness.

If the DVLA need to be notified, advise the person that it is their responsibility to do so.

The latest information from the DVLA regarding medical fitness to drive can be obtained at www.gov.uk/government/publications/at-a-glance.

Basis for recommendation

Basis for recommendation

This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2011].

Scenario: Pregnancy and breastfeeding

Scenario: Pregnancy and breastfeeding

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Pregnancy or breastfeeding

Women who are pregnant or breastfeeding with asthma: How do I manage?

Manage a woman who is pregnant like any other individual with asthma:

Continue the use of all medication as normal in pregnancy, but do not start leukotriene receptor antagonists. However, if the woman is already taking a leukotriene receptor antagonist and it is considered essential, continue treatment.

Advise women that the benefits of treatment with oral corticosteroids for an acute attack outweigh the risks.

Advise women who smoke about the dangers that smoking poses to themselves and their children. Give appropriate support for stopping smoking.

Encourage women with asthma to breastfeed their babies and use asthma medications as normal during breastfeeding.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

The risks from uncontrolled asthma are much greater than the risks from asthma treatments during pregnancy.

The risks of uncontrolled asthma in pregnancy include hyperemesis, hypertension, pre-eclampsia, vaginal haemorrhage, complicated labour, fetal growth restriction, pre-term birth, increased perinatal mortality, and neonatal hypoxia [Schatz et al, 1990; Perlow et al, 1992; Demissie et al, 1998; Dombrowski et al, 2004].

Women who have a severe exacerbation of asthma during pregnancy are at a significantly increased risk of having a low-birthweight baby compared with women without asthma [Murphy et al, 2006].

In contrast, if asthma is well controlled throughout pregnancy there is little or no increased risk of adverse maternal or fetal complications [Schatz et al, 1988; Schatz et al, 1995].

A case-control study including 2460 infants exposed to short-acting beta2-agonists found no increased risk of congenital malformation in exposed infants [Dombrowski et al, 2004].

A meta-analysis of four studies of inhaled corticosteroid use in pregnancy showed no increase in the rate of major malformations, pre-term delivery, low birth weight or pregnancy-induced hypertension [Rahimi et al, 2006]. A large UK population based case-control study found no increased risk of major congenital malformations in children of women receiving asthma treatment with inhaled beta2-agonists and inhaled corticosteroids in the year before or during pregnancy [Tata et al, 2008].

A systematic review of studies including 190 exposure to long-acting beta2-agonists demonstrated no increased risk of congenital malformations, pre-term delivery or per-eclampsia [Gluck and Gluck, 2005].

Oral corticosteroids are not teratogenic, although there are conflicting data on whether oral corticosteroids are associated with oral clefts. Expert opinion is that the association is not definite and, even if it is real, the benefit to the mother and her baby of using corticosteroids to treat a potentially life-threatening disease, justify their use in pregnancy [Schatz et al, 1990].

Leukotriene receptor antagonists should not be started during pregnancy because data on their safety in pregnant or breastfeeding women are limited [SIGN and BTS, 2011].

In two small prospective studies no increase in the rates of congenital malformation, preterm birth, or low-birthweight was found [Schaefer et al, 2007].

There have been several case reports of limb defects in women taking a leukotriene receptor antagonist during pregnancy, but a causal relationship has not been established [Schaefer et al, 2007].

Referral

When is a referral recommended in people with asthma?

The decision to refer is influenced by local referral pathways, the individual, and the experience of the primary healthcare provider.

In addition to respiratory physicians and paediatricians with a specialist interest in respiratory medicine, such specialists as dietitians, physiotherapists, occupational therapists, and respiratory nurse specialists may be involved in the management of asthma at any stage.

Admit or refer adults for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt:

Unexpected clinical findings (for example crackles, clubbing, cyanosis, cardiac disease).

Persistent non-variable breathlessness.

Monophonic, unilateral or fixed wheeze or stridor.

Persistent chest pain or atypical features.

Prominent systemic features, for example weight loss, myalgia, fever.

Persistent cough or sputum production.

Spirometric or peak expiratory flow measurements that do not fit the clinical picture, for example unexplained restrictive spirometry.

Suspected occupational asthma.

Non-resolving pneumonia.

Inadequate response to maximum guideline treatment.

Admit or refer children for specialist assessment or further investigation in the following situations:

The diagnosis is unclear or in doubt (the younger the child, the more difficult it is to be sure that wheezing is due to asthma):

Unexpected clinical findings (for example abnormal voice, focal chest signs, dysphagia, inspiratory wheeze, stridor).

Symptoms present from birth, or perinatal lung problem.

Excessive vomiting or posseting.

Severe upper respiratory tract infection.

Persistent productive cough.

Family history of unusual chest disease.

Failure to thrive.

Parental anxiety.

Inadequate response to maximum guideline treatment, particularly if oral corticosteroids are needed frequently, or use of the maximum dose of inhaled corticosteroids.

The urgency of a referral to secondary care or admission to hospital should be appropriate to the clinical situation.

For indications of when to admit someone with an acute exacerbation of asthma, see When to admit to hospital in Scenario: Acute asthma exacerbation.

Basis for recommendation

Basis for recommendation

These recommendations are based on the British guideline on the management of asthma: a national clinical guideline [SIGN and BTS, 2011].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Short-acting beta2-agonists

Prescribing a short-acting beta2-agonist

What do I need to know when prescribing a short-acting beta2-agonist?

Inhaled short-acting beta2-agonists should be used as required unless an individual has shown to benefit from regular use:

As-required use of short-acting beta2-agonists is at least as effective as regular administration [SIGN and BTS, 2011] and is less likely to result in tolerance.

Inhaled short-acting beta2-agonists have minimal adverse effects. Overuse can cause tremor, tension, headache, muscle cramps, and palpitations [BNF 53, 2007]. Hypokalaemia may result from high doses of inhaled beta2-agonists (or oral beta2-agonists); this may be potentiated by concomitant treatment with theophylline, corticosteroids, diuretics, and by hypoxia. The Committee on the Safety of Medicines has advised that plasma potassium should be monitored in people with severe asthma [CSM, 1990].

There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with short-acting beta2-agonists. The MHRA has issued advice that people with a history of heart disease, including angina or rhythm disturbance, should seek medical advice if symptoms such as shortness of breath or chest pain occur, as these may indicate worsening heart disease [MHRA, 2007].

Inhaled corticosteroids

Choosing an inhaled steroid

Which inhaled corticosteroid?

The various inhaled corticosteroids (ICS) do not seem to differ in efficacy (assuming a potency ratio of beclometasone and fluticasone of 2:1).

Adverse effects are class effects and do not differ significantly between the different inhaled corticosteroids (ICS) at either low or high doses. Increased doses of ICS are associated with an increased risk of local and systemic adverse effects. There is evidence that provided the recommended dose is used, ICS are effective and safe in children aged under 5 years [SIGN and BTS, 2011].

CKS recommends beclometasone, budesonide, or fluticasone because they are available in a range of formulations at different doses and for a range of ages.

Ciclesonide (available as a pressurized metered-dose inhaler) and mometasone (available as a dry-powder inhaler) are once-daily alternatives. Neither drug is licensed for children younger than 12 years. Mometasone has black triangle status and further post-marketing data are needed to confirm its safety.

Dose

Use the lowest dose of inhaled corticosteroid (ICS) that maintains effective control of asthma.

Start ICS at a dose appropriate to the severity of symptoms [SIGN and BTS, 2011]:

Suitable starting doses for beclometasone-CFC free as Clenil Modulite® are:

Age > 12 years: 200 micrograms twice daily.

Age 5–12 years: 100 micrograms twice daily.

Age < 5 years: 100 micrograms twice daily; higher doses may be required to ensure adequate drug delivery.

If beclometasone CFC-free is started as Qvar® use half the dose listed above (licensed only for age > 12 years).

Table 1 and Table 2 show comparable total daily doses of ICS.

Higher doses of ICS may be needed in people who smoke. At low doses, smokers with mild persistent asthma are less sensitive than non-smokers to the therapeutic effects of ICS treatment. This disparity is reduced at high doses of ICS [Tomlinson et al, 2005].

Treatment with ICS should initially be twice a day (except ciclesonide, which is licensed for once-a-day use) [SIGN and BTS, 2011]:

Most ICS are slightly more effective when used twice rather than once a day, but people with milder disease may use them once a day. There is little evidence of benefit for administration more frequently than twice a day.

Once-daily inhalation of ICS at the same total daily dose, within the product license, may be considered if good control is established.

Prescribe CFC-free beclometasone inhalers by brand name (Clenil Modulite® or Qvar®) [MHRA, 2006a]. They are not equivalent and must not be interchanged.

When changing from a CFC pMDI to a CFC-free pMDI [BNF 53, 2007; SIGN and BTS, 2011]:

Clenil Modulite® may be substituted for beclometasone CFC pMDI at 1:1 dosing.

Qvar® may be substituted for beclometasone CFC pMDI at 1:2 dosing if asthma is well controlled, but consider 1:1 dosing if asthma is poorly controlled. Monitor the person closely to ensure that adequate control is maintained.

Clarification / Additional information

Comparable doses of inhaled corticosteroids are shown in Table 1 (adults and children > 12 years of age) and Table 2 (children).

Beclometasone inhalers that contain chlorofluorocarbons (CFC) have been phased out and are no longer available.

Table 1 . Recommended daily doses of inhaled corticosteroid delivered by pressurized metered-dose inhaler (pMDI) for adults and children aged 12 years of age or older. Dosage adjustment may be necessary for alternative devices.
pMDI Age (Years) Dose of inhaled corticosteroid
Low dose Usual start dose (step 2) High dose (step 3) Maximum dose
Clenil Modulite® (beclometasone CFC-free) >12 100 micrograms twice daily 200 micrograms twice daily 400 micrograms twice daily 1000 micrograms twice daily
Qvar® (beclometasone CFC-free)* >12 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily 400 micrograms twice daily
Fluticasone‡ >12 50 micrograms twice daily 100 micrograms twice daily 250 micrograms twice daily 500 micrograms twice daily
*When converting from CFC beclometasone to Qvar®, double the dose in the table if control of asthma is poor. Note that this does not apply to Clenil Modulite®, which is equipotent. ‡The maximum licensed daily dose of fluticasone for adults is 2000 micrograms. The Committee on Safety of Medicines (CSM) has advised that doses of fluticasone above 1000 micrograms a day should only be prescribed for adults with severe asthma, and should only be initiated by a physician with a special interest in asthma [CSM, 2001]
Table 2 . Recommended daily doses of inhaled corticosteroid delivered by pressurized metered-dose inhaler (pMDI) for children < 12 years of age. Dosage adjustment may be necessary for alternative devices.
pMDI Age (years) Dose of inhaled corticosteroid
Low dose Ususal start dose (step 2) High dose (step 3) Maximum dose
Clenil Modulite®(Beclometasone CFC-free) 5–11 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily 400 micrograms twice daily (unlicensed)
< 5 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily
Qvar®(Beclometasone CFC-free)* < 12 Unlicensed for children under the age of 12
Budesonide 5–11 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily 400 micrograms twice daily
< 5 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily
Budesonide CFC-free 5–11 100 micrograms once daily 100 micrograms twice daily 200 micrograms twice daily 400 micrograms twice daily
2–5 100 micrograms once daily 100 micrograms twice daily 200 micrograms twice daily
< 2 Unlicensed for children < 2 years
Fluticasone 5–11 25 micrograms twice daily 50 micrograms twice daily 100 micrograms twice daily 200 micrograms twice daily
4 25 micrograms twice daily 50 micrograms twice daily 100 micrograms twice daily
< 4 Unlicensed for children < 4 years
* When converting from CFC beclometasone to Qvar®, double the dose in the table if control of asthma is poor. Note that this does not apply to Clenil Modulite®, which is equipotent. † In children under 5 years of age, doses higher than 200 micrograms twice a day of beclometasone (or equivalent ICS) should only be used under specialist supervision.

Adverse effects

What are the adverse effects of inhaled corticosteroids and how can they be managed?

Take into account the use of other systemic or topical corticosteroids when assessing risk.

Elderly people and children may be particularly susceptible to adverse effects.

Local adverse effects:

Oral candidiasis, sore mouth, dysphonia, and hoarseness are commonly recognized problems with inhaled corticosteroid (ICS) use, especially in high doses:

For people using a pressurized metered-dose inhaler, these effects may be reduced by using a large-volume spacer device (which reduces oropharyngeal deposition by filtering out larger particles) [DTB, 2000; RPSGB, 2006].

Oral candidiasis can be minimized by rinsing the mouth with water after ICS inhalation.

Oropharyngeal deposition is high with dry-powder inhalers and autohalers.

Systemic adverse effects — adults:

Osteoporosis: there are concerns that inhaled corticosteroids may affect bone mineral density, particularly when given in high doses for long periods, but the evidence regarding this is conflicting [SIGN and BTS, 2011]:

In people who require high doses of ICS for prolonged periods of time, general measures to counteract osteoporosis (such as regular exercise, smoking cessation, and adequate dietary calcium) are prudent.

Adrenal suppression: evidence indicates that high doses of ICS (equivalent to 1.5 mg/day CFC-containing beclometasone) result in significant adrenal suppression [EBM, 1999]. The risk of adrenal insufficiency is dose related and is largely due to use of oral corticosteroids, although inhaled corticosteroids may have an effect when they are taken at higher doses [Mortimer et al, 2006]:

Titrate the dose of inhaled steroid to the lowest dose at which effective control of asthma is maintained [SIGN and BTS, 2011].

Systemic adverse effects — children:

The Committee on Safety of Medicines has 'strongly advised that the paediatric licensed doses of all inhaled corticosteroids should not be exceeded' [CSM, 2002]. Use the lowest dose of ICS that will maintain disease control. If adequate control is not achieved, consider using add-on agents rather than increasing the dose of ICS [SIGN and BTS, 2011].

Childhood growth: some initial slowing of growth may occur in children who have used ICS, but final adult height does not appear to be affected [Childhood Asthma Management Program Research Group, 2000; MeReC, 2002]:

All children receiving prolonged treatment with ICS should have their height regularly and accurately monitored using a growth chart [CSM, 1998]. Any slowing of growth should prompt a reduction in dose if possible, or referral to a specialist, or both.

Bone mineral density: one long-term study in children with chronic asthma treated with ICS suggests no adverse effect of ICS on bone mineral density in children [Agertoft and Pedersen, 2000]. Further long-term studies are needed to confirm this. However, experts suggest that with careful ICS dose adjustment, this risk is likely to be outweighed by the ability of ICS to reduce the need for multiple courses of oral corticosteroids [Kelly et al, 2008].

Very rarely psychiatric disorders including psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, and behavioural changes (predominantly in children), have been reported [ABPI Medicines Compendium, 2011a].

Acute adrenal crisis: in a small number of children, doses of inhaled ICS at or above 400 micrograms per day of beclometasone have been associated with growth failure and adrenal suppression. The exact dose and duration of ICS treatment to put a child at risk of adrenal insufficiency is unknown, but it is likely to be 1000 micrograms or more of beclometasone or equivalent daily [SIGN and BTS, 2011]:

Specific written advice about steroid replacement in the event of a severe intercurrent illness should be part of the management plan for children treated with 800 micrograms or more of beclometasone or equivalent daily.

Any child receiving this dose should be under the care of a specialist paediatrician for the duration of the treatment.

Consider use of a steroid treatment card.

Consider the possibility of adrenal insufficiency in any child maintained on inhaled steroids presenting with shock or decreased consciousness:

Check serum biochemistry and blood glucose levels urgently.

Consider whether intramuscular hydrocortisone is required.

Advice for patients

Advise people that smoking can reduce the effectiveness of inhaled corticosteroids (ICS) [SIGN and BTS, 2011].

Advise people to rinse their mouth with water (or clean children's teeth) after inhalation of a dose of ICS to reduce the risk of oral candidiasis [BNF 53, 2007].

Advise on general measures to counteract osteoporosis (such as regular exercise, smoking cessation, and adequate calcium intake) in people using high doses of ICS for prolonged periods.

Advise parents to immediately report non-specific symptoms, such as anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased consciousness, hypoglycaemia, and seizures, in children using high doses of ICS (400 micrograms or more per day of beclometasone).

Consider use of a steroid treatment card:

People using prolonged high doses (off-label high doses, or maximum doses in conjunction with oral corticosteroids) of ICS should be given a steroid treatment card which gives guidance on minimizing risk and provides details of prescriber, drug, dosage, and duration of treatment [CHM, 2006].

Long-acting beta2-agonists

Prescribing a long-acting beta2-agonist

What do I need to know when prescribing a long-acting beta2-agonist?

The long-acting beta2-agonists (LABAs), salmeterol and formoterol, are well tolerated and have few adverse effects.

There has been concern regarding LABAs and an increase in asthma-related adverse events. On the basis of current evidence, the Medicines and Healthcare products Regulatory Agency has issued the following recommendations [MHRA, 2005]:

Long-acting beta2-agonists (LABAs) should not be prescribed for someone who is not already using an inhaled corticosteroid.

Inhaled corticosteroid treatment should not be stopped whilst the person is using a LABA.

People with acutely deteriorating asthma should not be started on LABA therapy.

People should be monitored closely, especially during the first 3 months of treatment.

Treatment with LABAs should be continued only if they have shown benefit.

Stepping-down therapy should be considered when good long-term asthma control has been achieved.

Salmeterol has a slower onset of action than salbutamol or terbutaline and should not be used to relieve an acute exacerbation of asthma [BNF 53, 2007].

A daily dose of 24 micrograms formoterol should be sufficient for most children, particularly younger age groups. Higher doses should be used rarely, and only when control is not maintained on the lower dose [MHRA, 2010].

Basis for recommendation

There has been concern regarding the safety of long-acting beta2-agonist (LABA) therapy.

The Salmeterol Multi-Centre Asthma Research Trial (SMART) [Nelson et al, 2006] was a large randomized controlled trial (n = 26,355) that compared salmeterol with placebo in older children and adults. The study was stopped prematurely because the incidence of asthma-related adverse effects (such as severe asthma exacerbations and asthma-related deaths) was higher in people who had used salmeterol without an inhaled corticosteroid (ICS):

The risk of adverse effects was higher in African-American people than in the white population.

The authors could not determine whether the negative outcomes in the trial were due to the physiological effect of the drug, genetic factors, behavioural factors, or combinations of these factors.

A meta-analysis pooled the results from 19 trials (n = 33,826 including the SMART study), and similarly concluded that LABA therapy increases severe and life-threatening asthma exacerbations, and risk of asthma-related death [Salpeter et al, 2006].

Using a long-acting beta2-agonist

Advise people who are starting treatment with a long-acting beta2-agonist (LABA) to report any deterioration in symptoms [BNF 53, 2007].

Advise people using a LABA that they must not stop using their inhaled corticosteroid (ICS).

Advise people who have been prescribed salmeterol that they should not use it to relieve an acute asthma attack.

Advise people who are inhaling terbutaline using a turbohaler to rinse their mouth after each use. A fraction of the dose will always be deposited in the mouth and rinsing the mouth will minimize the amount of terbutaline absorbed systemically [ABPI Medicines Compendium, 2011b].

Theophylline

Prescribing issues

The margin between therapeutic and toxic doses of theophylline is narrow. Most people require plasma concentrations between 10 and 20 mg/L for satisfactory bronchodilation, although a lower concentration may be effective.

Once a maintenance dose has been reached, check serum theophylline concentration every 6 to 12 months, or if the person is experiencing adverse effects that might suggest toxicity [UKMI, 2002].

Adverse effects, including nausea, vomiting, tremor, palpitations, and arrhythmias, can occur at plasma concentrations of 10–20 mg/L. The frequency and severity of adverse effects increase with concentrations greater than 20 mg/L.

Serum levels of theophylline are increased (because of an increase in the half-life of theophylline) in people with heart failure or hepatic impairment, in elderly people, and by drugs that inhibit hepatic enzymes (for example cimetidine, ciprofloxacin, erythromycin, fluvoxamine, St John's Wort):

If people whose disease is stable during theophylline therapy begin to take one of these drugs, a reduction of the theophylline dose is recommended.

Serum levels of theophylline are decreased (because of a decrease in the half-life of theophylline) in people who smoke, in chronic alcohol misuse, and by drugs that induce hepatic enzymes (for example phenytoin, carbamazepine, rifampicin):

If people whose disease is stable during theophylline therapy begin to take one of those drugs, the theophylline dose may need to be increased.

If people whose disease is stable during theophylline therapy stop smoking, plasma levels of theophylline may increase, and a reduction in dose may be necessary.

When prescribing theophylline, the brand should be specified on the prescription. Because of differences in bioavailability among brands, people should be maintained on the same brand of theophylline.

Leukotriene receptor antagonists

Prescribing a leukotriene receptor antagonist

The leukotriene receptor antagonists montelukast and zafirlukast are well tolerated and have few class-related adverse effects [GINA, 2006].

Zafirlukast has been associated with liver toxicity. If clinical symptoms or signs suggestive of liver dysfunction occur (for example anorexia, nausea, vomiting, right upper quadrant pain, fatigue, lethargy, flu-like symptoms, enlarged liver, pruritus, or jaundice), stop zafirlukast and immediately measure serum transaminases (in particular, serum alanine aminotransferase). Routine monitoring of liver function is not recommended [ABPI Medicines Compendium, 2004].

Use in children: montelukast is the only leukotriene receptor antagonist licensed for use in children (aged 6 months and older). A paediatric granule formulation is available, which can be swallowed or mixed with cold or room-temperature soft food and taken immediately [ABPI Medicines Compendium, 2007].

Use in pregnancy: do not start a leukotriene receptor antagonist during pregnancy. However, if a woman is already taking a leukotriene receptor antagonist and it is considered essential, treatment can be continued during pregnancy [SIGN and BTS, 2011].

In two small prospective studies no increase in the rates of congenital malformation, preterm birth, or low-birthweight was found. There have been several case reports of limb defects in women taking a leukotriene receptor antagonist during pregnancy, but a causal relationship has not been established [Schaefer et al, 2007].

Advice for patients

Advise people taking zafirlukast to seek medical advice in the event of persistent nausea, vomiting, malaise, or jaundice [BNF 53, 2007].

Advise the person that montelukast should not be used to relieve symptoms of an acute asthma exacerbation.

Cromones

Cromones (sodium cromoglicate and nedocromil sodium)

Advice for using an inhaled cromone

Advise people that inhaled sodium cromoglicate or nedocromil sodium should be used regularly, usually four times a day.

Cromone inhalers should not be used to relieve an acute attack of asthma.

If inhalation of the dry powder form of sodium cromoglicate causes bronchospasm, advise the person to use their short-acting beta2-agonist inhaler (salbutamol or terbutaline) a few minutes prior to using the sodium cromoglicate inhaler.

Oral corticosteroids

Prescribing oral corticosteroids

Adverse effects are uncommon with infrequent, short courses of oral corticosteroids.

Table 1 in managing people not needing admission shows the dose of oral prednisolone recommended in an acute exacerbation of asthma:

In adults, oral corticosteroids should be continued for at least 5 days, until recovery.

In children, oral corticosteroids should be continued for at least 3 days, until recovery.

Prescribe soluble prednisolone tablets for children who cannot swallow tablets.

Repeat the dose of prednisolone in children who vomit.

After recovery from the acute exacerbation, therapy with prednisolone can be stopped abruptly, without tapering the dose, unless the course was longer than 3 weeks or the person was previously receiving maintenance oral corticosteroid treatment.

Adverse effects

What are the adverse effects of continuous or frequent use of oral corticosteroids and how can they be managed?

The risk and severity of adverse effects with oral corticosteroids increase with the dose and the duration of treatment. People receiving long-term oral corticosteroids (more than 3 months) or those needing frequent courses of an oral corticosteroid (three to four per year) are at risk of systemic adverse effects.

Systemic adverse effects include osteoporosis, hypertension, diabetes, hypothalamic–pituitary–adrenal axis suppression, weight gain, cataracts, glaucoma, skin-thinning, easy bruising, and muscle weakness.

Aim to prevent, minimize, or quickly detect adverse effects of long-term corticosteroids. General and lifestyle recommendations to minimize adverse effects include the following:

Encourage adequate dietary calcium intake and good nutrition.

Maintain normal body weight where possible.

Advise on smoking cessation.

Advise on moderate alcohol consumption.

Encourage physical exercise within the limits imposed by the underlying disease.

Perform a falls risk assessment, where appropriate, and advise those at increased risk of fractures from falling.

Monitor, prevent, and treat the systemic adverse effects of continuous or frequent courses of oral corticosteroids:

Blood pressure: monitor regularly and treat if necessary.

Diabetes mellitus: screen regularly and treat if necessary.

Osteoporosis: see the CKS topic on Osteoporosis - prevention of fragility fractures for details on when to prescribe prophylactic bisphosphonate therapy.

Growth suppression: record height of children regularly and accurately.

Cataracts: screen children periodically through community optometric services.

Children who frequently use courses of oral corticosteroids should have regular checks for signs of adrenal suppression. Refer to a paediatrician who can arrange Synacthen® testing, where appropriate.

Document the person's history of chickenpox (fatal disseminated chickenpox may occur in non-immune people). Advise all people without a history of chickenpox who are taking systemic prednisolone to avoid close contact with people who have chickenpox or shingles, and to seek urgent medical advice if they are exposed.

Evidence

Evidence

Supporting evidence

Stable asthma

Evidence on stable asthma

Short-acting beta2-agonists

Evidence on short-acting beta2-agonists

There is no clinically significant difference between regular or as-required short-acting beta2-agonists in terms of lung function, use of reliever medication, exacerbation rates, or quality of life:

One systematic review (search date 2002, 22 crossover randomized controlled trials [RCTs] and eight parallel-group RCTs) examined regular versus as-required use of short-acting beta2-agonists in asthma control. Most studies did not allow concomitant use of inhaled corticosteroids, and only data from the crossover studies were suitable for pooling. The review found no difference in morning peak flow rates, but regular use improved evening peak flow rates, reduced diurnal variation, and reduced the need for reliever medication. However, the clinical relevance of these results is uncertain, because exacerbation rates, and quality-of-life scores did not differ and one RCT (n = 117) showed better symptom control over 24 hours with as-required use than with regular use. In some studies, regular use was associated with deterioration of airway responsiveness after stopping medication, increased allergen-induced bronchoconstriction, and tremor [Rodolfo et al, 2005].

Inhaled corticosteroids

Evidence on inhaled corticosteroids

ICS versus placebo:

One systematic review (search date 1999, 12 randomized controlled trials [RCTs], n = 647) and seven subsequent RCTs (six RCTs, n = 1210; one RCT, n = 7241) involved budesonide. One systematic review (search date 2004, seven RCTs, n = 1043) involved fluticasone (100 or 200 micrograms/day). One systematic review (search date 2003, 10 RCTs, n = 1458) examined beclometasone and seven RCTs (n = 2788) examined triamcinolone, flunisolide, mometasone, and ciclesonide. All studies involved people with mild asthma and showed that ICS improved lung function, improved asthma symptoms, and reduced the need for bronchodilator therapy compared with placebo. Only the fluticasone systematic review showed that fluticasone significantly increased the risk of oral candidiasis compared with placebo (2% versus 0.5%; RR 3.45, 95% CI 1.29 to 9.26). The other reviews may have been underpowered to detect a clinically important difference [Rodolfo et al, 2005].

ICS versus short-acting beta2-agonist:

One systematic review (no search date, five RCTs [of which two compared beta2-agonists], n = 141) showed that ICS significantly improved lung function compared with beta2-agonists. No information was provided on adverse effects [Rodolfo et al, 2005].

ICS versus sodium cromoglicate:

A Cochrane review (search date February 2004) included 17 trials (n = 1279 children > 2 years of age) and eight trials (n = 321 adults) of people with moderate-to-severe asthma that made head-to-head comparisons of ICS against sodium cromoglicate. Inhaled corticosteroids were superior to sodium cromoglicate for all outcomes, such as reduced exacerbation rates (primary outcome), asthma symptom scores, peak flow rates, and need for rescue medication in children and adults (secondary outcomes). Adverse effects did not differ between groups, although inconsistent reporting and lack of long-term follow up prevent drawing firm conclusions about safety. The results are generalizable, but the studies did not involve infants younger than 2 years and older people (> 65 years) [Guevara et al, 2006].

ICS versus leukotriene receptor antagonists:

A systematic review (13 RCTs, 12 in adults, one in children) in people with mild-to-moderate asthma compared ICS (doses equivalent to beclometasone, 400 micrograms/day) with leukotriene receptor antagonists. Inhaled corticosteroids were more effective at reducing exacerbations, nocturnal awakenings, use of rescue beta2-agonists, and days with symptoms. Adverse effects did not differ between groups, but more people in the leukotriene receptor antagonist group withdrew because of poor asthma control [Ducharme, 2003]:

An RCT (n = 994) randomized children 6–14 years of age with mild persistent asthma to receive inhaled fluticasone, 100 micrograms twice daily, or oral montelukast, 5 mg once daily, for 1 year. The results favoured ICS over montelukast. The ICS group had more rescue-free days (mean 86.7% versus 84%); this result was statistically significantly in favour of fluticasone but is of questionable clinical significance. The fluticasone group had a lower proportion of children requiring systemic corticosteroids and a lower proportion with asthma attack [Garcia Garcia et al, 2005].

Fluticasone versus hydrofluoroalkane-134a (HFA)-beclometasone dipropionate:

A Cochrane review (search date January 2007) involving eight RCTs (n = 1260, only one study involving children) showed no statistically significant difference between both ICS on lung function over 6 to 12 weeks. However, this should not be taken as equivalence, as the data available could not exclude a meaningful benefit of fluticasone over HFA-beclometasone dipropionate. Data on exacerbation rates, symptom scores, and rescue medication use were very limited, but overall, no differences were reported. Adverse effects did not differ between groups, and very few adverse effects were recorded, which may due to the short duration of many of the studies. These findings cannot be generalized to children or people with a poor inhaler technique. Further research is needed to validate the effects reported in these studies [Lasserson et al, 2006].

Long-acting beta2-agonists

Evidence on long-acting beta2-agonists

LABA versus placebo:

Four randomized controlled trials (RCTs) (n = 2063) in people with persistent asthma not controlled with beclometasone, 200 to 2000 micrograms/day, showed that the addition of salmeterol or formoterol improved peak expiratory flow rate, forced expiratory volume in 1 second (FEV1) and reduced night awakening compared with placebo. The studies involving salmeterol also showed improvements in quality-of-life scores compared with placebo. In the formoterol trials, symptoms were improved significantly at 6 months. However, exacerbation rates did not differ between groups in any RCT [Rodolfo et al, 2005].

A systematic review (search date June 2004, 26 RCTs [eight on children, 18 on adults]) randomized people to an ICS alone (beclometasone, 200 to 400 g/day or equivalent) or an ICS with LABAs (formoterol or salmeterol). Most trials lasted 4 months or less. The addition of LABA reduced risk of exacerbations requiring systemic steroids (NNT 18, 95% CI 13 to 33), and increased the proportion of symptom-free days by 17% (95% CI 12 to 22) in 6 trials, increased the proportion of rescue-free days by 19% (95% CI 12 to 26) in two trials, and reduced use of rescue short-acting beta2-agonists by 0.7 puff/day (95% CI –1.2 to –0.2 puff/day) [Ni Chroinin et al, 2005]. A later Cochrane review supports the benefits of LABA therapy in terms of lung function, fewer symptoms, less use of rescue medication, and improved quality-of-life score compared with placebo. However, the risk of exacerbations in children may have been increased; this finding needs further confirmation [Walters et al, 2007].

In a systematic review (search date July 2005) of ten parallel-group randomized trials, two studies showed that in adults, the addition of a LABA to ICS allows reduction of the ICS dose. The groups did not significantly differ in the rates of severe exacerbations requiring oral corticosteroids and withdrawal due to worsening asthma, and LABA therapy was associated with significant improvements in FEV1, peak expiratory flow rate, and percentage of rescue-free days [Gibson et al, 2005].

LABA versus increasing ICS:

A systematic review (search date July 2005, 30 RCTs, n = 9509, children > 2 years of age [three trials] and adults [27 trials]) compared a combination of LABA plus ICS with a higher dose of ICS. The combination regimen significantly increased symptom-free days by 12% (eight trials), reduced daytime use of rescue beta2-agonists by 1 puff/day (four trials), and reduced the rate of withdrawals owing to poor asthma control (20 trials). The groups did not significantly differ in the rate of exacerbations requiring systemic steroids (15 trials) or overall adverse events (15 trials). Tremor was the only significant adverse effect that was increased with LABA therapy (10 trials) [Greenstone et al, 2005].

One systematic review (search date 1999, nine RCTs) and eight additional RCTs found that adding LABA (salmeterol or formoterol) to ICS improved lung function and symptoms compared with increasing the ICS dose. Addition of LABA reduced exacerbation rates. However, one RCT found that increasing ICS compared with adding formoterol significantly reduced severe exacerbations at 1 year [Rodolfo et al, 2005].

An RCT (n = 1272) showed that formoterol was more effective than doubling the dose of budesonide at 1 year for reducing the risk of severe exacerbations and poorly controlled asthma days [O'Byrne et al, 2001].

LABA versus leukotriene receptor antagonists:

Seven RCTs (total n = 3943) compared salmeterol or formoterol with leukotriene receptor antagonists (montelukast or zafirlukast). All studies had slightly different results, but overall, LABA improved lung function and symptoms more than leukotriene receptor antagonists. One of the larger RCTs (n = 1490) showed no significant difference in asthma exacerbations over 48 weeks between fluticasone plus salmeterol and fluticasone plus montelukast (19.1% vs. 20.1%; difference 1%, 95% CI –3.1 to +5) [Rodolfo et al, 2005]. A recent Cochrane review (15 RCTs, 11 RCTs included in the meta-analysis, n = 6030) supports the findings of early RCTs and adds that LABA lower the risk of exacerbations requiring systemic corticosteroids (NNT 38 to prevent one exacerbation over 48 weeks, 95% CI 23 to 247) compared with leukotriene receptor antagonists [Ducharme et al, 2006].

LABA versus theophylline:

A systematic review (search date April 2003, 12 RCTs) showed LABA to be at least as effective as theophylline in reducing symptoms (including night awakening) and improving lung function. However, LABA were associated with less adverse effects than theophylline. A later systematic review (search date November 2006, 13 RCTs, n = 1344) confirmed these findings and suggested that LABA were more effective than theophylline in improving morning and evening peak expiratory flow rate. Salmeterol decreased the need for short-acting beta2-agonist compared with theophylline [Tee et al, 2007].

LABA adverse effects:

One RCT (Salmeterol Multicenter Asthma Research Trial [SMART], n = 26,355 people > 12 years of age) showed that salmeterol significantly increased the number of respiratory-related deaths (RR 2.16, 95% CI 1.06 to 4.41), asthma-related deaths (RR 4.37, 95% CI 1.25 to 15.3; NNH 1315), and combined asthma-related deaths or life-threatening experiences (RR 1.71, 95% CI 1.01 to 2.89; NNH 909). Mortality in the RCT was very low: the number needed to harm (one asthma-related death) was 1318 (95% CI 746 to 6173) after a mean of 7 months. Whether this increased risk represents lack of appropriate use of ICS, a treatment effect, or genetic factors is not yet clear [Nelson et al, 2006]. A Cochrane review (search date October 2005, 67 RCTs, n = 42,333) highlights that these observations were drawn from a post hoc analysis and lack the validity of pre-defined distinctions. The review also states that LABA used in appropriate candidates, along with ICS, are very safe [Walters et al, 2007].

A systematic review (19 RCTs, n = 33,836) including the SMART trial showed that use of LABA (salmeterol and formoterol) for at least 3 months (range 3–12 months) compared with placebo resulted in hospitalization for asthma exacerbation in 1.72% versus 0.6% (NNH 89) based on meta-analysis of 12 trials (n = 5091), and life-threatening asthma exacerbations in 0.32% versus 0.17% (NNH 666) based on meta-analysis of seven trials (n = 29,981). There were 15 versus 3 asthma-related deaths in 14 trials with reported asthma-related deaths (NNH 1428, 95% CI 1000 to 10,000). In sensitivity analysis that assumed no deaths in 28 additional trials, the absolute increase in risk was 0.06% (NNH 1666) [Salpeter et al, 2006].

Leukotriene receptor antagonists

Evidence on leukotriene receptor antagonists

Leukotriene receptor antagonists versus placebo in people using ICS:

A systematic review (search date October 2003, 27 RCTs, only two trials included children) showed that addition of a leukotriene receptor antagonist to ICS reduced the risk of exacerbations requiring systemic steroids (not statistically significant), reduced use of rescue short-acting beta2-agonists (by 1 puff/week), and improved peak expiratory flow rate (by 7.7 mL/min). Only three trials compared addition of leukotriene receptor antagonists with increasing the inhaled steroid dose, and no conclusions can be made [Ducharme et al, 2004].

An RCT (n = 455 adults) with asthma and skin-test sensitivity to seasonal aeroallergens were randomized to receive oral montelukast 10 mg vs. placebo for 3 weeks during the allergy season. The reduction in daytime asthma symptom score (total 6 points) was 0.54 points with montelukast and 0.34 points with placebo, a statistically significant (p = 0.002) but not clinically relevant difference [Busse et al, 2006].

An RCT (n = 689 children aged 2–5 years) showed that 12 weeks of montelukast, 4 mg once daily, was more effective than once-daily chewable placebo tablets at improving daytime asthma symptoms (59% vs. 64% days with asthma symptoms), nocturnal cough, and use of beta2-agonists (49% vs. 55% days with beta-agonist use) and use of oral steroids. No significant adverse effects were reported [Knorr et al, 2001].

Leukotriene receptor antagonist versus doubling the dose of ICS:

An RCT (n = 889 people aged 15–75 years) showed that addition of montelukast (10 mg once daily) and doubling the dose of budesonide were equally effective strategies in people whose asthma was inadequately controlled with budesonide, 800 micrograms/day, over 12 weeks. Both groups improved, and more rapid response was reported in the montelukast group, but this finding was based on peak flow measurements. The groups did not significantly differ in symptom-based outcomes. The study was funded by the manufacturer of montelukast [Rodolfo et al, 2005].

Leukotriene receptor antagonist alone versus ICS alone:

One systematic review (search date 2003, 15 RCTs in adults and three RCTs in children, n = 4965) found that leukotriene receptor antagonists were significantly less effective than ICS (beclometasone and fluticasone) in reducing risk of exacerbation requiring oral corticosteroids and reducing symptom-free days over 4 to 37 weeks. There was no difference in hospital admission rates for exacerbations [Rodolfo et al, 2005].

Leukotriene receptor antagonists alone versus ICS plus LABA:

Two RCTs (n = 855 adults) showed that fluticasone (200 micrograms/day) plus salmeterol (50 mg/day) compared with montelukast (10 mg/day) significantly increased symptom-free days, reduced exacerbations, and improved lung function and symptoms at 12 weeks [Rodolfo et al, 2005].

Theophylline

Evidence on theophylline

The evidence for theophylline use in asthma is limited and of poor quality. Results of head-to-head studies comparing theophylline with other add-on therapies are inconsistent and require further, more robust evaluation. Overall, theophylline appears to be more beneficial than placebo and is at best similar in effectiveness to long-acting beta2-agonists, sodium cromoglicate, and leukotriene receptor antagonists. However, increasing the dose of inhaled corticosteroids (ICS) provides better asthma control than adding in theophylline in poorly controlled asthma. In all comparison studies, theophylline is associated with an increased risk of adverse effects:

A systematic review (search date May 2006, 35 randomized controlled trials [RCTs], n = 2754) compared oral xanthines (for example theophylline) in children aged 18 months to 18 years [Seddon et al, 2006]:

Placebo (18 RCTs): xanthine increased the proportion of symptom-free days by 8% (95% CI 3.4 to 12.5) and decreased use of rescue medication, but symptom scores and hospitalizations did not significantly differ.

ICS (four RCTs): exacerbations were less frequent and symptom improvements were better with ICS, and xanthines were associated with more frequent headaches and nausea. There was no significant difference in lung function.

Regular short-acting beta2-agonists (ten RCTs): these agents did not significantly affect symptoms or use of rescue medication. They reduced hospitalizations and headaches but increased tremor.

Sodium cromoglicate (six RCTs): no significant differences in symptoms, exacerbations, or rescue medication use were observed. Xanthines had more gastrointestinal adverse effects.

A recent RCT (n = 489) randomized people with poorly controlled asthma to placebo, theophylline 300 mg/day, or montelukast 10 mg/day, for 24 weeks. Rates of episodes of poor asthma control, asthma symptoms, and quality of life did not differ significantly among groups. Theophylline and montelukast provided small improvements in the pre-bronchodilator forced expiratory volume in 1 second, which were of borderline significance. However, in people not taking ICS, asthma control, symptoms, and lung function improved more with low-dose theophylline than with montelukast or placebo [American Lung Association Asthma Clinical Research Centers, 2007].

Cromones

Evidence on cromones

Cromones may be of some benefit in adults and children older than 5 years to help with asthma symptoms, but the evidence is inconclusive. Sodium cromoglicate offers no clear benefit in children aged 5 years or younger [SIGN and BTS, 2011]:

A systematic review (24 double-blind randomized controlled trials [RCTs], n = 1074 children) concluded that sodium cromoglicate may have a small overall treatment effect; however, this finding lacked statistical significance, and the likelihood of publication bias was high. The authors concluded that sodium cromoglicate should not be used as first-line therapy in asthma management [Tasche et al, 2000].

A systematic review (15 randomized controlled trials, n = 1422 children) concluded that nedocromil may reduce symptoms in children with asthma, but the longer-term evidence of symptom benefit is limited and inconsistent. More evidence is required on nedocromil compared with inhaled corticosteroids, whose efficacy is well established in asthma. In short-term studies, nedocromil showed promising results compared with placebo, especially in terms of lung function. However, the primary endpoint of symptom-free days was inconsistent in the longer-term studies. The only significant adverse effect was unpleasant taste [Sridhar and McKean, 2006].

Symbicort Smart®

Evidence on Symbicort Smart® for maintenance and reliever therapy for asthma management

Symbicort SMART® compared with ICS + long-acting beta2-agonist (adults)

One Cochrane systematic review (search date September 2008, five randomized open controlled trials) found that Symbicort SMART® was no different to current best practice (ICS plus long-acting beta2-agonist) [Cates and Lasserson, 2009].

Exacerbations of asthma requiring treatment with oral corticosteroids: OR 0.83, 95% CI 0.66 to 1.03 (n = 4,470).

Exacerbations requiring hospital admissions: OR 0.59, 95% CI 0.24 to 1.45 (n = 5378).

There was no difference in the rate of fatal or non-fatal adverse events (data from three studies). The event rates were too low to rule out a clinically significant increase or decrease in adverse events.

Another four studies comparing Symbicort SMART® with current best practice are due for completion soon, and the results from a further 4600 participants are awaited.

Symbicort SMART® compared with ICS alone (adults and adolescents)

The same Cochrane systematic review (search date September 2008, three randomized, double-blind controlled trials, one randomized open controlled trial) found that Symbicort SMART® was no different to ICS alone for exacerbations needing hospital admission, but there were fewer exacerbations requiring oral corticosteroids [Cates and Lasserson, 2009]. One study compared Symbicort SMART® to the same dose of ICS. Three studies compared Symbicort SMART ® to increased dose ICS. Patients were withdrawn from their long-acting beta2-agonist in the ICS arms. The authors argue that this could have led to an increase in early exacerbations in patients taking ICS because an increase in the ICS dose would be expected to take longer to work than the long-acting beta2-agonist component in Symbicort®.

Exacerbations of asthma requiring treatment with oral corticosteroids: OR 0.54, 95% CI 0.45 to 0.64 (n = 4280).

Exacerbations requiring hospital admission: OR 0.56, 95% CI 0.28 to 1.09 (n = 4209).

There was no difference in the rate of fatal or non-fatal adverse events (data from three studies). The event rates were too low to rule out a clinically significant increase or decrease in adverse events.

Self-management education and action plans

Evidence on self-management education and action plans

People experience one-third to two-thirds reduction in hospitalizations, emergency department visits, missed days of work, and nocturnal wakening. Implementation of one self-management programme in 20 people prevents one hospitalization. Less intensive interventions (not involving a written action plan) appear to be less effective [GINA, 2006].

Written action plans improve health outcomes for people with asthma, as part of self-management education. The evidence is particularly good for people who have had a recent exacerbation [Gallefoss and Bakke, 2000; Moudgil et al, 2000; Cote et al, 2001; Guevara et al, 2003; Gibson and Powell, 2004; Rodolfo et al, 2005; Rees, 2006; SIGN and BTS, 2011]:

A systematic review (search date November 2004, four randomized controlled trials, n = 355) suggested that children prefer symptom-based monitoring action plans over peak flow-based monitoring action plans (RR 1.21, 95% CI 1.00 to 1.46), but parents showed no preference. Exacerbation rates, admissions, school absenteeism, lung function, symptom score, quality of life, and withdrawals did not differ significantly between types of action plans [Bhogal et al, 2006].

Self-management education:

In children and adolescents, self-management education can reduce symptoms, school absenteeism, and visits to emergency treatment services [Guevara et al, 2003; Bhogal et al, 2006]. There is less evidence of benefit of written action plans for very young children [Haby et al, 2001; Wolf et al, 2002; DTB, 2005].

In teenagers, innovative approaches, such as web-based or peer-based delivery (at school), appear to be more successful than traditional programmes [SIGN and BTS, 2011].

Lifestyle interventions

Evidence on lifestyle interventions

The evidence for lifestyle interventions in asthma management is based on a few small studies. Most of the trial evidence is inconsistent, however smoking cessation (by the individual or parent of a child with asthma) and weight reduction (in obese people) improve asthma symptoms. Larger, more robust studies of allergen avoidance are needed to confirm benefit:

Smoking:

There is a direct causal relationship between parental smoking and lower respiratory tract illness in children up to 3 years of age. Infants whose mothers smoke are four times more likely to develop wheezing illnesses in the first year of life [GINA, 2006].

Exposure to tobacco contributes to the severity of childhood asthma. Average exposure is associated with a 30% increased risk of asthma symptoms. One small study suggests that, by stopping smoking, parents can decrease the severity of asthma in their children [SIGN and BTS, 2011].

Vaccinations:

A systematic review (search date August 2003, nine randomized controlled trials [RCTs]) concluded that evidence is insufficient to determine whether influenza vaccination prevents exacerbations in people with asthma, but influenza vaccination with inactive vaccine does not cause exacerbations [Cates et al, 2003].

A systematic review (search date 2001 September) including only one RCT (n = 30 children) of poor methodological quality (lack of blinding and inadequate allocation concealment), showed that pneumococcal vaccination decreased the incidence of acute asthma exacerbations per child (from ten to seven episodes per year) in those with asthma prone to recurrent episodes of otitis media [Sheikh et al, 2002].

Allergen avoidance:

Aero-allergen avoidance trials have shown inconsistent effects on asthma. Air pollution may provoke or aggravate an acute asthma attack, but this trigger is minimal compared with an infectious trigger [SIGN and BTS, 2011].

Two Cochrane reviews suggest that measures to control house dust mite allergens do not appear to be a cost-effective method of treating asthma. Studies were heterogeneous in terms of intervention, and allocation was not adequately concealed in some studies. At present, there is no clear benefit of house dust mite avoidance [Woodcock et al, 2003; GINA, 2006; SIGN and BTS, 2011].

Results of observational studies are conflicting and have not shown that removing a pet from the home improves asthma control [SIGN and BTS, 2011].

Weight reduction, diet, and exercise:

An open study of two randomized parallel groups of obese people with asthma found that a supervised weight-reduction programme significantly improved lung function, symptoms, morbidity, and health status [Stenius-Aarniala et al, 2000]. A smaller study found that weight loss reduces airways obstruction and peak flow variability in obese people with asthma [Hakala et al, 2000].

There is no convincing evidence from Cochrane reviews to support the use of fish oil supplements, salt restriction, or tartrazine exclusion in the management of asthma [SIGN and BTS, 2011].

A Cochrane review (13 RCTs, n = 455) showed that physical training increases cardiorespiratory capacity but has no effect on lung function and days of wheezing in people with asthma. Evidence is insufficient on the role of breathing exercises in the management of asthma to recommend any one particular technique [Ram et al, 2005]. Nevertheless, some small studies have suggested a possible benefit in asthma symptoms with the Buteyko [Cooper et al, 2003] and Papworth [Holloway and West, 2007] methods of breathing. These findings need further confirmation.

Associated conditions:

Rhinitis: one study showed that 76% of people with asthma had symptoms of rhinitis. Half of these people said their rhinitis made their asthma worse [Pinnock and Shah, 2007]. Rhinitis usually comes before asthma, and it is both a risk factor for asthma and is associated with increased severity of the disease [GINA, 2006]. The treatment of allergic rhinitis has not been shown to improve asthma control [SIGN and BTS, 2011].

Gastro-oesophageal reflux disease: the relationship of increased asthma symptoms, particularly at night, to gastro-oesophageal reflux remains uncertain, although the condition is three times more prevalent in people with asthma than in the general population [GINA, 2006]. A Cochrane review (12 RCTs) concluded that the treatment of gastro-oesophageal reflux in people with asthma had no effect on asthma symptoms or lung function. Dry cough improved, although this symptom was probably not due to asthma [SIGN and BTS, 2011].

Hay fever: there is a strong link between asthma and hay fever, and deaths from asthma in young adults peak during the pollen season [Pinnock and Shah, 2007].

Acute asthma exacerbation

Evidence on acute asthma exacerbation

Trigger factors

Evidence on trigger factors

The evidence on trigger factors for exacerbation of asthma comes from small case-controlled studies. Viruses appear to be a common trigger, whilst bacterial infections are a much less common cause [GINA, 2006; SIGN and BTS, 2011]:

Small case-controlled studies in children have shown respiratory syncytial virus to be associated with wheezing in infancy. Rhinovirus (the cause of common cold) is the principal cause of wheezing and worsening asthma in older children and adults. Other viruses, such as parainfluenza and enterovirus, are also associated with worsening asthma symptoms.

Small case-controlled studies have identified atypical bacteria (Chlamydia pneumoniae and Mycoplasma pneumoniae) as a much less frequent cause of worsening asthma, but their exact role remains uncertain.

Inhaled beta2-agonists

Evidence on inhaled beta2-agonists

Most studies of inhaled beta2-agonists were done in Accident and Emergency departments and involved monitoring people over 1–6 hours; the findings are therefore difficult to generalize to primary care. However, continuous beta2-agonist treatment or the addition of ipratropium bromide appears to reduce the number of people hospitalized with a severe asthma exacerbation:

Beta2-agonist dose and frequency:

A randomized controlled trial (RCT, n = 100) in adults with acute asthma showed that six sprays of salbutamol via a metered-dose inhaler every 60 minutes was safe and effective, but some people who did not respond initially may benefit from treatment 30 minutes after the first inhalation. Treatment intervals of 60 minutes (compared with 30 minutes or 120 minutes) seemed to provide optimal results in most people, and hospitalization rates and adverse events did not differ [Karpel et al, 1997].

Beta2-agonists via a pressurized metered-dosed inhaler versus a nebulizer:

A systematic review (six RCTs, n = 491 children < 5 years of age) showed a metered-dose inhaler with a spacer to be more effective than a nebulizer. The children who received nebulizers had higher admission rates [Castro-Rodriguez and Rodrigo, 2004]. Children are less likely to have tachycardia and hypoxia when using a pressurized metered-dose inhaler with spacer compared with a nebulizer [SIGN and BTS, 2011].

Continuous versus intermittent beta2-agonists:

One systematic review (search date 2004, eight RCTs, n = 461) found that continuous nebulized beta2-agonists significantly reduce hospital admission compared with intermittent nebulized beta2-agonists, especially in people with severe airflow obstruction (RR 0.64, 95% CI 0.50 to 0.90). Adverse effects, such as heart rate and blood pressure elevation and tremor, did not differ between groups [Rodolfo et al, 2005].

Ipratropium bromide added to beta2-agonists:

Two systematic reviews and one subsequent RCT found that the addition of ipratropium bromide to beta2-agonists in acute severe asthma improves lung function and is likely to reduce hospital admission [Rodolfo et al, 2005].

Oral corticosteroids

Evidence on oral corticosteroids

Systemic corticosteroids versus placebo:

One systematic review (search date 1991, five RCTs, n = 422) found that early intervention with systemic corticosteroids (oral, intravenous, or intramuscular) significantly reduced hospitalizations compared with placebo (OR 0.47, 95% CI 0.27 to 0.79). Another systematic review (five RCTs, n = 345) showed that systemic corticosteroids (oral or intramuscular) significantly reduced the relapse rate at 7–10 days (RR 0.35, 95% CI 0.17 to 0.73; NNT 13) and hospital readmission within 7 days (RR 0.32, 95% CI 0.11 to 0.94; NNT 16) compared with placebo. Corticosteroids also significantly reduced the use of beta2-agonists [Rodolfo et al, 2005].

A later systematic review (search date September 2000, 12 RCTs, n = 863) of corticosteroids given within 1 hour to people presenting to the emergency department with acute asthma further supports these findings. Early administration of corticosteroids significantly reduced admission rates (11 trials; pooled OR 0.4, 95% CI 0.21 to 0.78; NNT 8, 95% CI 5 to 21), and benefits were more pronounced for people not already receiving systemic corticosteroids and people with more severe asthma. Oral corticosteroids were particularly effective in children (three RCTs) [Rowe et al, 2001].

Stopping treatment:

A small RCT (n = 35) of people admitted to hospital for asthma who were given 40 mg of prednisolone over 10 days showed no difference in morning peak expiratory flow rate between tapering over 1 week and abruptly stopping therapy (p = 0.82) [Rodolfo et al, 2005].

Dose and duration:

Three small RCTs showed no difference in dose and duration (5–10 days) of corticosteroids with regard to lung function and relapse rates. Nevertheless, all three RCTs may have lacked the power to detect a clinically important difference. The optimum dose and duration is likely to depend on the individual, severity of the exacerbation, and concomitant medication [Rodolfo et al, 2005].

Corticosteroids in children:

A systematic review (17 RCTs) showed oral corticosteroids to be effective for outpatient treatment of acute asthma in children. Early administration of oral corticosteroids appeared to reduce hospitalizations [Rachelefsky, 2003].

A systematic review (search date May 2006, two RCTs, n = 303) showed that when parents initiated oral corticosteroid therapy for an intermittent wheezing illness (asthma, viral wheeze, and preschool viral wheeze), there was no significant benefit in terms of hospital admissions, symptom scores, bronchodilator use, parental and patient impressions, or days lost from school [Vuillermin et al, 2006].

Inhaled cortisosteroids

Evidence on inhaled corticosteroids

Inhaled corticosteroids (ICS) have been shown in small randomized controlled trials (RCTs) to provide benefit in asthma management in terms of reducing hospital admissions compared with placebo. No consistent evidence indicates that doubling the dose of ICS improves peak expiratory flow rate (PEFR) and symptoms compared with continuing the usual dose of ICS. Use of ICS in addition to oral corticosteroids offers no benefit in preventing asthma exacerbations [Rodolfo et al, 2005]:

Increasing the ICS dose at early signs of an exacerbation does not appear to benefit management of an exacerbation:

ICS versus placebo:

One systematic review (search date February 2005, 10 RCTs, n = 587) in adults and children attending an emergency department showed that ICS reduced hospital admission. Subgroup analysis found that the benefit was significant only in people not receiving concomitant oral corticosteroids (OR 0.27, 95% CI 0.14 to 0.52). Treatment with ICS was well tolerated, with few reported adverse effects.

An RCT (n = 390) showed that doubling the dose of ICS for worsening PEFR and symptoms was no better than continuing therapy with the regular dose. People at risk of exacerbation monitored their morning peak flow and symptoms for up to 12 months. They were randomly assigned to use an active inhaler or a placebo inhaler and to double the usual dose for 14 days if their PEFR or symptoms deteriorated. Results showed no difference in use of oral corticosteroids (11% vs. 12%) or symptom scores [Harrison et al, 2004].

ICS plus oral corticosteroids versus oral corticosteroids alone:

One systematic review (search date 2003, three RCTs, n = 909) showed that in adults attending an emergency department, relapse rates after 24 days did not differ significantly with either regimen (OR 0.68, 95% CI 0.46 to 1.02) [Rodolfo et al, 2005].

ICS versus oral corticosteroids:

One systematic review (search date 2001, four RCTs, 772 adults and 22 children) showed no significant difference in relapse rates at 7–10 days in people receiving oral prednisolone or ICS (equivalent to beclometasone, 2000 micrograms/day) for an acute asthma exacerbation (OR 1.00, 95% CI 0.66 to 1.52, p = 0.88). One subsequent RCT (n = 40) in adults discharged from hospital following an exacerbation showed no difference in lung function or symptoms between oral prednisolone and inhaled flunisolide at 7 days. An additional RCT (n = 413) showed no significant difference in treatment failure with oral prednisolone and high-dose inhaled fluticasone (2000 micrograms/day) in people presenting to their GP for an asthma exacerbation [Rodolfo et al, 2005].

Further small studies have shown conflicting evidence of ICS compared with oral corticosteroids in children with acute asthma. Overall, oral corticosteroids appear to be superior to ICS, but trials are heterogeneous, making it difficult to draw definite conclusions [Schuh et al, 2006].

Montelukast

Montelukast

There is evidence from two small randomized trials that montelukast given to children aged over 2 years with mild asthma may reduce symptoms and subsequent hospital attendance. There is no evidence for its use other than for a mild exacerbation of asthma.

A randomized, double-blind, placebo-controlled, parallel-group study included 51 children aged 2–5 years who were using a short acting beta2-agonist intermittently and who had a clinical history of intermittent asthma [Harmanci et al, 2006]. During an acute attack the children were randomized to receive montelukast (n = 25) or placebo (n = 26). Clinical improvement was assessed by a pulmonary index score which had five parameters: air entry, wheezing, supra sternal retractions, abdominal breathing, and oxygen saturation. The score was measured at half hourly intervals for 4 hours.

After 90 minutes there was a significant improvement in the pulmonary index score in the group receiving montelukast.

A randomized, double-blind, placebo-controlled, multicentre trial included 220 children with intermittent asthma who were randomized to receive either montelukast (n = 107) or placebo (n = 113) during an acute exacerbation of asthma [Robertson et al, 2007]. There were 163 exacerbations of asthma over 12 months in the group receiving montelukast and 228 exacerbations in the placebo group [Robertson et al, 2007].

There was a significant reduction in nights awakened by 8.6% (p = 0.43), days off from school by 37% (p< 0.0001), and parent time off from work by 33% (p<0.0001).

A randomized, double-blind, placebo-controlled, pilot study enrolled children aged 6–14 years who presented with an acute asthma exacerbation of moderate severity (PEFR  = 40–70% of predicted) [Nelson et al, 2008]. The children were randomized to receive either oral montelukast or placebo at the beginning of their treatment. FEV1 was measured before the start of treatment and then hourly until 3 hours post treatment.

There was no improvement in FEV1 at 3 hours.

The authors concluded that in children with moderate asthma, oral montelukast is unlikely to result in improvement in FEV1.

Exercise-induced asthma

Evidence on exercise-induced asthma

The evidence for medication in exercise-induced asthma is limited to small randomized controlled trials (RCTs). Different study designs and dose and duration of medication make it difficult to draw definite conclusions. Overall, short-acting beta2-agonists appear to be the most cost-effective therapy for preventing symptoms of exercise-induced asthma. Very few head-to-head studies have been conducted, and no evidence is available for children younger than 5 years:

Long-acting beta2-agonists (LABAs): in small RCTs, LABAs were more effective than placebo in controlling exercise-induced asthma, but no more effective than short-acting beta2-agonists. The benefit appears to decrease with long-term use [SIGN and BTS, 2011]:

An RCT crossover trial (n = 24 children) showed formoterol to be similar to terbutaline in bronchodilator effect for exercise-induced asthma [Hermansen et al, 2006].

An RCT (n = 20 adults) compared salmeterol (twice daily for 1 month) with placebo. All participants underwent 30 minutes of exercise after the morning dose and 9 hours later. The benefits appeared to be minimal at 9 hours, especially on days 14 and 29 [Nelson et al, 1998].

Leukotriene receptor antagonists: most evidence is available for montelukast.

When taken regularly, montelukast appears to be more effective than placebo and at least as effective as LABAs (especially over the longer term) in preventing exercise-induced asthma. Montelukast may provide some benefit in preventing bronchospasm by use of a single dose before exercise, but larger studies are needed to confirm this [Pearlman et al, 2006].

Cromones (nedocromil and sodium cromoglicate):

A systematic review (search date September 2001, 20 trials, n = 280) showed that nedocromil given before an exercise challenge test appears to be effective at preventing exercise-induced asthma, especially in people with more severe bronchoconstriction [Spooner et al, 2002].

A systematic review (search date March 2000, eight RCTs, children > 6 years of age) showed no significant difference between sodium cromoglicate or nedocromil (at different doses) in preventing or reducing exercise-induced asthma symptoms for up to 2 hours [Kelly et al, 2000].

References

ABPI Medicines Compendium (2004) Summary of product characteristics for Accolate. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2007) Summary of product characteristics for Singulair paediatric 4mg granules. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2010) Summary of product characteristics for Xolair 150 mg powder and solvent for solution for injection. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2011a) Summary of product characteristics for Clenil Modulite 50, 100, 200, 250 micrograms inhaler. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2011b) Summary of product characteristics for Bricanyl Turbohaler, 0.5mg/dose, inhalation powder. Electronic Medicines CompendiumDatapharm Communications Ltd. www.medicines.org.uk [Free Full-text]

Agertoft, L. and Pedersen, S. (2000) Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. New England Journal of Medicine 343(15), 1064-1069. [Abstract] [Free Full-text]

American Lung Association Asthma Clinical Research Centers (2007) Clinical trial of low-dose theophylline and montelukast in patients with poorly controlled asthma. American Journal of Respiratory and Critical Care Medicine 175(3), 235-242. [Abstract] [Free Full-text]

Anderson, H.R. (2005) Prevalence of asthma. British Medical Journal 330(7499), 1037-1038. [Free Full-text]

Asthma UK (2006) Where do we stand? Asthma in the UK today. Asthma UK. www.asthma.org.uk

Bernard-Bonnin, A.C., Stachenko, S., Bonin, D. et al. (1995) Self-management teaching programs and morbidity of pediatric asthma: a meta-analysis. Journal of Allergy and Clinical Immunology 95(1), 34-41. [Abstract]

Bhogal, S., Zemek, R. and Ducharme, F.M. (2006) Written action plans for asthma in children (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

BMA and NHS Employers (2011) Summary of 2011/12 QOF indicator changes, points and thresholds. BMA and NHS Employers. www.nhsemployers.org [Free Full-text]

BMA and NHS Employers (2012) Quality and outcomes framework for 2012/13. Guidance for PCOs and practices. BMA and NHS Employers. www.bma.org.uk [Free Full-text]

BMA and NHS Employers (2013) Summary of QOF changes for 2013/14 in England. British Medical Association and NHS Employers. www.nhsemployers.org [Free Full-text]

BNF 53 (2007) British National Formulary. 53rd edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

BNF for Children (2007) British National Formulary for children. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain.

Brocklebank, D., Wright, J. and Cates, C. (2001) Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma. British Medical Journal 323(7318), 896-900. [Abstract] [Free Full-text]

Burr, M.L., Wat, D., Evans, C. et al. (2006) Asthma prevalence in 1973, 1988 and 2003. Thorax 61(4), 296-299. [Abstract] [Free Full-text]

Busse, W.W., Casale, T.B., Dykewicz, M.S. et al. (2006) Efficacy of montelukast during the allergy season in patients with chronic asthma and seasonal aeroallergen sensitivity. Annals of Allergy, Asthma & Immunology 96(1), 60-68. [Abstract]

Castro-Rodriguez, J.A. and Rodrigo, G.J. (2004) beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis. Journal of Pediatrics 145(2), 172-177. [Abstract]

Cates, C.J. and Lasserson, T.J. (2009) Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Cates, C.J., Jefferson, T.O., Bara, A.I. and Rowe, B.H. (2003) Vaccines for preventing influenza in people with asthma (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com

Childhood Asthma Management Program Research Group (2000) Long-term effects of budesonide or nedocromil in children with asthma. New England Journal of Medicine 343(15), 1054-1063. [Abstract] [Free Full-text]

CHM (2006) High dose of inhaled steroids: new advice on supply of steroid treatment cards. Current Problems in Pharmacovigilance 31(May), 5. [Free Full-text]

Cooper, S., Oborne, J., Newton, S. et al. (2003) Effect of two breathing exercise (Buteyko and pranayama) in asthma: a randomised controlled trial. Thorax 58(8), 674-679. [Abstract] [Free Full-text]

Cote, J., Bowie, D.M., Robichaud, P. et al. (2001) Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation. American Journal of Respiratory and Critical Care Medicine 163(6), 1415-1419. [Abstract] [Free Full-text]

CSM (1990) Beta-agonists, xanthines and hypokalaemia. Current Problems in Pharmacovigilance 28(May), 3. [Free Full-text]

CSM (1998) Focus on corticosteroids. Current Problems in Pharmacovigilance 24(May), 5-10. [Free Full-text]

CSM (2001) Reminder: fluticasone propionate (Flixotide): use of high doses (>500 micrograms/twice daily). Current Problems in Pharmacovigilance 27(Aug), 10. [Free Full-text]

CSM (2002) Inhaled corticosteroids and adrenal suppression in children. Current Problems in Pharmacovigilance 28(Oct), 7. [Free Full-text]

Currie, G.P., Devereux, G.S., Lee, D.K. and Ayres, J.G. (2005) Recent developments in asthma management. British Medical Journal 330(7491), 585-589. [Free Full-text]

de Marco, R., Locatelli, F., Sunyer, J. and Burney, P. (2000) Differences in incidence of reported asthma related to age in men and women. A retrospective analysis of the data of the European Respiratory Health Survey. American Journal of Respiratory and Critical Care Medicine 162(1), 68-74. [Abstract] [Free Full-text]

Demissie, K., Breckenridge, M.B. and Rhoads, G.G. (1998) Infant and maternal outcomes in the pregnancies of asthmatic women. American Journal of Respiratory and Critical Care Medicine 158(4), 1091-1095. [Abstract] [Free Full-text]

DH (2006a) Immunisation against infectious disease - "The Green Book". Chapter 2 - Consent. Department of Health. www.dh.gov.uk [Free Full-text]

DH (2006b) Immunisation against infectious disease - "The Green Book". Chapter 25 - Pneumococcal. Department of Health. www.dh.gov.uk [Free Full-text]

Dolovich, M.B., Ahrens, R.C., Hess, D.R. et al. (2005) Device selection and outcomes of aerosol therapy: evidence-based guidelines. Chest 127(1), 335-371. [Abstract] [Free Full-text]

Dombrowski, M.P., Schatz, M., Wise, R. et al. (2004) Asthma during pregnancy. Obstetrics and Gynecology 103(1), 5-12. [Abstract]

Doull, I.J. (2004) The effect of asthma and its treatment on growth. Archives of Disease in Childhood 89(1), 60-63. [Abstract] [Free Full-text]

DTB (2000) Inhaler devices for asthma. Drug & Therapeutics Bulletin 38(2), 9-14. [Abstract]

DTB (2005) Action plans in asthma. Drug & Therapeutics Bulletin 43(12), 91-94. [Abstract]

Ducharme, F.M. (2003) Inhaled glucocorticoids versus leukotriene receptor antagonists as single agent asthma treatment: systematic review of current evidence. British Medical Journal 326(7390), 621. [Abstract] [Free Full-text]

Ducharme, F., Schwartz, Z. and Kakuma, R. (2004) Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Ducharme, F.M., Lasserson, T.J. and Cates, C.J. (2006) Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

DVLA (2010) At a glance guide to the current medical standards of fitness to drive (August update). Driver and Vehicle Licensing Agency. www.gov.uk [Free Full-text]

DVLA (2011) At a glance guide to the current medical standards of fitness to drive (February 2011). Driver and Vehicle Licensing Agency. www.gov.uk [Free Full-text]

EBM (1999) High-dose inhaled corticosteroids increase the risk for some systemic adverse effects in asthma. Evidence-Based Medicine 4(6), 191.

Gallefoss, F. and Bakke, P.S. (2000) Impact of patient education and self-management on morbidity in asthmatics and patients with chronic obstructive pulmonary disease. Respiratory Medicine 94(3), 279-287. [Abstract]

Garcia Garcia, M.L., Wahn, U., Gilles, L. et al. (2005) Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC Study. Pediatrics 116(2), 360-369. [Abstract] [Free Full-text]

Gibson, P.G. and Powell, H. (2004) Written action plans for asthma: an evidence-based review of the key components. Thorax 59(2), 94-99. [Abstract] [Free Full-text]

Gibson, P.G., Powell, H. and Ducharme, F. (2005) Long-acting beta2-agonists as an inhaled corticosteroid-sparing agent for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

GINA (2006) Global strategy for asthma management and prevention. Global Initiative for Asthma.

Giraud, V. and Roche, N. (2002) Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. European Respiratory Journal 19(2), 246-251. [Abstract] [Free Full-text]

Gluck, J.C. and Gluck, P.A. (2005) Asthma controller therapy during pregnancy. American Journal of Obstetrics and Gynecology 192(2), 369-380. [Abstract]

Green, R.M., Custovic, A., Sanderson, G. et al. (2002) Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. British Medical Journal 324(7340), 763. [Abstract] [Free Full-text]

Greenstone, I.R., Ni Chroinin, M.N., Masse, V. et al. (2005) Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Guevara, J.P., Wolf, F.M., Grum, C.M. and Clark, N.M. (2003) Effects of educational interventions for self management of asthma in children and adolescents: systematic review and meta-analysis. British Medical Journal 326(7402), 1308-1309. [Abstract] [Free Full-text]

Guevara, J.P., Ducharme, F.M., Keren, R. et al. (2006) Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Haby, M.M., Waters, E., Robertson, C.F. et al. (2001) Interventions for educating children who have attended the emergency room for asthma (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Hakala, K., Stenius-Aarniala, B. and Sovijarvi, A. (2000) Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma. Chest 118(5), 1315-1321. [Abstract] [Free Full-text]

Harmanci, K., Bakirtas, A., Turktas, I. and Degim, T. (2006) Oral montelukast treatment of preschool-aged children with acute asthma. Annals of Allergy, Asthma and Immunology 96(5), 731-735. [Abstract]

Harrison, T.W., Oborne, J., Newton, S. and Tattersfield, A.E. (2004) Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 363(9405), 271-275. [Abstract]

Hermansen, M.N., Nielsen, K.G., Buchvald, F. et al. (2006) Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma. Chest 129(5), 1203-1209. [Abstract] [Free Full-text]

Holloway, E.A. and West, R. (2007) Integrated breathing and relaxation training (the Papworth Method) for adults with asthma in primary care: a randomised controlled trial. Thorax 62(12), 1039-1042. [Abstract] [Free Full-text]

Horak, E., Lanigan, A., Roberts, M. et al. (2003) Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42. British Medical Journal 326(7386), 422-423. [Free Full-text]

Karpel, J.P., Aldrich, T.K., Prezant, D.J. et al. (1997) Emergency treatment of acute asthma with albuterol metered-dose inhaler plus holding chamber: how often should treatments be administered? Chest 112(2), 348-356. [Abstract] [Free Full-text]

Keahey, L., Bulloch, B., Becker, A.B. et al. (2002) Initial oxygen saturation as a predictor of admission in children presenting to the emergency department with acute asthma. Annals of Emergency Medicine 40(3), 300-307. [Abstract]

Keeley, D. and McKean, M. (2006) Asthma and other wheezing disorders in children. Clinical EvidenceBMJ Publishing Group Ltd. www.clinicalevidence.com

Kelly, K., Spooner, C.H. and Rowe, B.H. (2000) Nedocromil sodium versus sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Kelly, A., Tang, R., Becker, S. and Stanley, C.A. (2008) Poor specificity of low growth hormone and cortisol levels during fasting hypoglycemia for the diagnoses of growth hormone deficiency and adrenal insufficiency. Pediatrics 122(3), e522-e528. [Abstract] [Free Full-text]

Knorr, B., Franchi, L.M., Bisgaard, H. et al. (2001) Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 108(3), E48. [Abstract] [Free Full-text]

Lai, C.K., Beasley, R., Crane, J. et al. (2009) Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study fo Asthma and Allergies in Childhood (ISAAC). Thorax 64(6), 476-483. [Abstract]

Lasserson, T.J., Cates, C.J., Jones, A.B. et al. (2006) Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

McCormick, A., Fleming, D. and Charlton, J. (1995) Morbidity statistics from general practice. Fourth national study 1991-1992. Office of Population Censuses and Surveys. www.statistics.gov.uk

MeReC (2002) Chronic asthma. MeReC Briefing 18(Jun), 1-5. [Free Full-text]

MHRA (2005) Reminder: Salmeterol (Serevent) and formoterol (Oxis, Foradil) in asthma management. Medicines and Healthcare Products Regulatory Agency. www.mhra.gov.uk [Free Full-text]

MHRA (2006a) Beclometasone dipropionate pressurised metered dose inhaler. Important information. Medicines and Healthcare Products Regulatory Agency. www.mhra.gov.uk

MHRA (2006b) Reintroduction of the volumatic spacer device: important new information. Medicines and Healthcare Products Regulatory Agency. www.mhra.gov.uk

MHRA (2007) Short-acting beta agonists: myocardial ischaemia. Drug Safety Update 1(5), 10. [Free Full-text]

MHRA (2008) Long-acting beta2 agonists for asthma: review. Drug Safety Update 1(6), 9. [Free Full-text]

MHRA (2010) Long-acting β2-agonists: reminder for use in children and adults. Drug Safety Update 4(2), H2. [Free Full-text]

Molimard, M., Raherison, C., Lignot, S. et al. (2003) Assessment of handling or inhaler devices in real life: an observational study in 3811 patients in primary care. Journal of Aerosol Medicine 16(3), 249-254. [Abstract]

Mortimer, K., Tata, L.J., Smith, C.J.P. et al. (2006) Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study. Thorax 61(5), 405-408. [Abstract] [Free Full-text]

Moudgil, H., Marshall, T. and Honeybourne, D. (2000) Asthma education and quality of life in the community: a randomised controlled study to evaluate the impact on white European and Indian subcontinent ethnic groups from socioeconomically deprived areas in Birmingham, UK. Thorax 55(3), 177-183. [Abstract] [Free Full-text]

Murphy, V.E., Clifton, V.L. and Gibson, P.G. (2006) Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax 61(2), 169-176. [Abstract] [Free Full-text]

Nathan, J.A., Pearce, L., Field, C. et al. (2006) A randomized controlled trial of follow-up of patients discharged from the hospital following acute asthma: best performed by specialist nurse or doctor? Chest 130(1), 51-57. [Abstract] [Free Full-text]

Nelson, J., Strauss, L., Skowronski, M. et al. (1998) Effect of long-term salmeterol treatment on exercise-induced asthma. New England Journal of Medicine 339(3), 141-145. [Abstract] [Free Full-text]

Nelson, H.S., Weiss, S.T., Bleecker, E.R. et al. (2006) The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 129(1), 15-26. [Abstract] [Free Full-text]

Nelson, K.A., Smith, S.R., Trinkaus, K. and Jaffe, D.M. (2008) Pilot study of oral montelukast added to standard therapy for acute asthma exacerbations in children aged 6 to 14 years. Pediatric Emergency Care 24(1), 21-27. [Abstract]

Newman Taylor, A.J. (2003) Asthma. In: Warrell, D.A., Cox, T.M., Firth, J.D. and Benz, E.J. (Eds.) Oxford textbook of medicine. 4th edn. Oxford: Oxford University Press.

NICE (2000) Guidance on the use of inhaler systems (devices) in children under the age of 5 years with chronic asthma (NICE technology appraisal 10). National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2002) Inhaler devices for routine treatment of chronic asthma in older children (aged 5 - 15 years) (NICE technology appraisal 38). National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2008) Inhaled corticosteroids for the treatment of chronic asthma in adults and in children ages 12 years and over (NICE technology appraisal 138). National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

NICE (2013) Key therapeutic topics - medicines management options for local implementation. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

Ni Chroinin, M., Greenstone, I.R., Danish, A. et al. (2005) Long-acting beta2-agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma (Cochrane Review). The Cochrane LibraryJohn Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Nicolai, T., Pereszlenyiova-Bliznakova, L., Illi, S. et al. (2003) Longitudinal follow-up of the changing gender ratio in asthma from childhood to adulthood: role of delayed manifestation in girls. Pediatric Allergy and Immunology 14(4), 280-283. [Abstract]

NPC (2011) Key therapeutic topics 2010/11 - Medicines management options for local implementation. National Prescribing Centre. www.npc.nhs.uk [Free Full-text]

NPC (2012) Key therapeutic topics - medicines management options for local implementation. National Prescribing Centre. www.npc.nhs.uk [Free Full-text]

O'Byrne, P.M., Barnes, P.J., Rodriguez-Roisin, R. et al. (2001) Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. American Journal of Respiratory and Critical Care Medicine 164(8 Pt 1), 1392-1397. [Abstract] [Free Full-text]

Opolski, M. and Wilson, I. (2005) Asthma and depression: a pragmatic review of the literature and recommendations for future research. Clinical Practice and Epidemiology in Mental Health 1(Sep), 18. [Abstract] [Free Full-text]

Pearlman, D.S., van Adelsberg, J., Philip, G. et al. (2006) Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast. Annals of Allergy, Asthma and Immunology 97(1), 98-104. [Abstract]

Pearson, M.G. and Bucknall, C.E. (Eds.) (1999) Measuring clinical outcome in asthma. London: The Royal College of Physicians.

Perlow, J.H., Montgomery, D., Morgan, M.A. et al. (1992) Severity of asthma and perinatal outcome. American Journal of Obstetrics and Gynecology 167(4 Pt 1), 963-967. [Abstract]

Phelan, P.D., Robertson, C.F. and Olinsky, A. (2002) The Melbourne Asthma Study: 1964-1999. Journal of Allergy and Clinical Immunology 109(2), 189-194. [Abstract]

Pinnock, H. and Shah, R. (2007) Asthma. BMJ Masterclass for GPs. British Medical Journal 334(7598), 847-850. [Free Full-text]

Rachelefsky, G. (2003) Treating exacerbations of asthma in children: the role of systemic corticosteroids. Pediatrics 112(2), 382-397. [Abstract] [Free Full-text]

Rahimi, R., Nikfar, S. and Abdollahi, M. (2006) Meta-analysis finds use of inhaled corticosteroids during pregnancy safe: a systematic meta-analysis review. Human & Experimental Toxicology 25(8), 447-52. [Abstract]

Ram, F.S., Wright, J., Brocklebank, D. and White, J.E. (2001) Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering beta2 agonists bronchodilators in asthma. British Medical Journal 323(7318), 901-905. [Abstract] [Free Full-text]

Ram, F.S.F., Robinson, S.M., Black, P.N. and Picot, J. (2005) Physical training for asthma (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Rees, J. (2006) Asthma control in adults. British Medical Journal 332(7544), 767-771. [Free Full-text]

Robertson, C.F. (2002) Long-term outcome of childhood asthma. Medical Journal of Australia 177(Suppl), S42-S44. [Abstract]

Robertson, C.F., Price, D., Henry, R. et al. (2007) Short-course montelukast for intermittent asthma in children: a randomized controlled trial. American Journal of Respirtory and Critical Care 175(4), 323-329. [Abstract] [Free Full-text]

Rodolfo, J.D., Solarte, I. and Fitzgerald, J.M. (2005) Asthma. Clinical EvidenceBMJ Publishing Group Ltd. www.clinicalevidence.com

Rowe, B.H., Spooner, C., Ducharme, F.M. et al. (2001) Early emergency department treatment of acute asthma with systemic corticosteroids (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

RPSGB (2006) Practice guidance on the care of people with asthma and chronic pulmonary disease [Withdrawn]. Royal Pharmaceutical Society of Great Britain. www.rpharms.com

Salpeter, S.R., Buckley, N.S., Ormiston, T.M. and Salpeter, E.E. (2006) Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Annals of Internal Medicine 144(12), 904-912. [Abstract] [Free Full-text]

Schaefer, C., Peters, P. and Miller, R.K. (Eds.) (2007) Drugs during pregnancy and lactation: treatment options and risk assessment. 2nd edn. Oxford: Academic Press.

Schatz, M., Harden, K., Forsythe, A. et al. (1988) The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis. Journal of Allergy and Clinical Immunology 81(3), 509-517. [Abstract]

Schatz, M., Zeiger, R.S. and Hoffman, C.P. (1990) Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study Group. Chest 98(2), 389-392. [Abstract] [Free Full-text]

Schatz, M., Zeiger, R.S., Hoffman, C.P. et al. (1995) Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis. American Journal of Respiratory and Critical Care Medicine 151(4), 1170-1174. [Abstract]

Schuh, S., Dick, P.T., Stephens, D. et al. (2006) High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics 118(2), 644-650. [Abstract] [Free Full-text]

Seddon, P., Bara, A., Ducharme, F.M. and Lasserson, T.J. (2006) Oral xanthines as maintenance treatment for asthma in children (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Sheikh, A., Alves, B. and Dhami, S. (2002) Pneumococcal vaccine for asthma (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons Ltd. www.thecochranelibrary.com [Free Full-text]

SIGN and BTS (2005) 2005 update to the British guideline on the management of asthma [Withdrawn]. Scottish Intercollegiate Guidelines Network and British Thoracic Society. www.sign.ac.uk

SIGN and BTS (2008a) British guideline on the management of asthma: a national clinical guideline. Scottish Intercollegiate Guidelines Network and British Thoracic Society. www.sign.ac.uk [Free Full-text]

SIGN and BTS (2008b) British guideline on the management of asthma: a national clinical guideline (revised 2009). Scottish Intercollegiate Guidelines Network and The British Thoracic Society. www.sign.ac.uk [Free Full-text]

SIGN and BTS (2011) British guideline on the management of asthma: a national clinical guideline (revised 2011). Scottish Intercollegiate Guidelines Network and The British Thoracic Society. www.sign.ac.uk [Free Full-text]

Spooner, C.H., Saunders, L.D. and Rowe, B.H. (2002) Nedocromil sodium for preventing exercise-induced bronchoconstriction (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Sridhar, A.V. and McKean, M. (2006) Nedocromil sodium for chronic asthma in children (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Stenius-Aarniala, B., Poussa, T., Kvarnstrom, J. et al. (2000) Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study. British Medical Journal 320(7238), 827-832. [Abstract] [Free Full-text]

Tasche, M.J., Uijen, J.H., Bernsen, R.M. et al. (2000) Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 55(11), 913-920. [Abstract] [Free Full-text]

Tata, L.J., Lewis, S.A., McKeever, T.M. et al. (2008) Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax 63(11), 981-987. [Abstract]

Tee, A.K.H., Koh, M.S., Gibson, P.G. et al. (2007) Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Thomson, N.C., Chaudhuri, R. and Livingston, E. (2004) Asthma and cigarette smoking. European Respiratory Journal 24(5), 822-833. [Abstract] [Free Full-text]

Tomlinson, J.E.M., McMahon, A.D., Chaudhuri, R. et al. (2005) Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax 60(4), 282-287. [Abstract] [Free Full-text]

UKMI (2002) Monitoring drug therapy. North West Drug Information Letter. No. 120. UK Medicines Information. www.ukmi.nhs.uk [Free Full-text]

Vuillermin, P., South, M. and Robertson, C. (2006) Parent-initiated oral corticosteroid therapy for intermittent wheezing illnesses in children (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Walters, E.H., Gibson, P.G., Lasserson, T.J. and Walters, J.A.E. (2007) Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]

Warner, J. (2006) Personal communication. Consultant in Paediatrics, Imperial College, St Mary's Hospital: London.

Wolf, F.M., Guevara, J.P., Grum, C.M. et al. (2002) Educational interventions for asthma in children (Cochrane Review). The Cochrane Library. Issue 4. John Wiley & Sons Ltd. www.thecochranelibrary.com [Free Full-text]

Wolthers, O.D. (2002) Growth problems in children with asthma. Hormone Research 57(Suppl 2), 83-87. [Abstract]

Woodcock, A., Forster, L., Matthews, E. et al. (2003) Control of exposure to mite allergen and allergen impermeable bed covers for adults with asthma. New England Journal of Medicine 349(3), 225-236. [Abstract] [Free Full-text]