Bronchiectasis
Bronchiectasis - Summary
Bronchiectasis is a permanent dilatation and thickening of the airways associated with chronic cough, sputum production, bacterial colonization, and recurrent infection.
Bronchiectasis is caused by chronic inflammation of the airways and is associated with a wide range of diseases.
It is estimated that around 1 in 1000 adults in the UK have bronchiectasis and it is more common in women than in men.
The prognosis for bronchiectasis varies widely. Most people have few or no symptoms and a normal life expectancy. More severe disease results in daily symptoms, progressive loss of lung function, and a reduced life expectancy.
The prognosis is worse if the person has extensive disease, has frequent exacerbations, is colonized by Pseudomonas aeruginosa, and/or smokes.
Complications of bronchiectasis include:
Respiratory complications.
Right heart failure, secondary to chronic respiratory disease.
Reduced quality of life.
Urinary incontinence and sexual problems.
Chronic tiredness.
Nutritional deficiency.
Bronchiectasis should be suspected in:
Adults with a chronic cough.
Adults thought to have chronic obstructive pulmonary disease, who do not smoke, or who have frequent or prolonged exacerbations.
Children or adults with unexplained haemoptysis (usually recurrent blood-streaked sputum).
Children with a chronic cough (usually productive).
Children thought to have asthma that responds poorly to treatment.
Symptoms of bronchiectasis include:
Cough.
Breathlessness.
Haemoptysis.
Chest pain that is present between exacerbations and is usually non-pleuritic.
Signs of bronchiectasis include:
Course crackles during early inspiration.
Wheeze.
Large airway rhonchi (low pitched snore-like sound).
Finger clubbing — occurs very infrequently.
If bronchiectasis is suspected, the following should be arranged:
A chest x-ray to exclude other causes of chronic cough (such as lung cancer).
Referral to a respiratory physician to confirm the diagnosis and determine the underlying cause of bronchiectasis.
An infective exacerbation of bronchiectasis requiring antibiotic therapy can be diagnosed when there is:
Acute deterioration (usually over several days), with worsening cough (with increased sputum volume, viscosity, or purulence; with or without increasing wheeze, breathlessness, or haemoptysis) and/or systemic upset.
The presence of mucopurulent or purulent sputum alone, or the isolation of a pathogen alone, without deterioration in symptoms is not necessarily an indication for antibiotic treatment, particularly in adults.
An infective exacerbation of bronchiectasis can be managed in primary care. However, in some cases, hospital admission may be required (for example if the person is confused or has a temperature of 38°C or more).
Previous microbiology cultures, when available, should guide antibiotic choice for the treatment of bronchiectasis.
If previous microbiology cultures are not available:
Antibiotics should be prescribed according to local protocols where available, or
Amoxicillin is the first-line choice; alternatives for people allergic to penicillin include clarithromycin, erythromycin, or doxycycline (adults only).
Have I got the right topic?
This CKS topic covers the detection and management, in primary care, of bronchiectasis unrelated to cystic fibrosis in children and adults.
This CKS topic does not cover bronchiectasis caused by cystic fibrosis.
There are separate CKS topics on Asthma and Chronic obstructive pulmonary disease.
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.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
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].
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.
April 2011 — minor update. Change to recommendation regarding need for additional contraception during or after a course of antibiotics - additional contraception is no longer required when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less [FSRH, 2011]. Issued in June 2011.
April to August 2010 — This is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.
Update
New evidence
Evidence-based guidelines
Guidelines published since the last revision of this topic:
Pasteur, M.C., Bilton, D., Hill, A.T., and British Thoracic Society Bronchiectasis non-CF Guideline Group (2010) British Thoracic Society guideline for non-CF bronchiectasis. Thorax 65(Suppl 1), i1-1i58. [Abstract] [Free Full-text (pdf)] **This CKS topic is consistent with the recommendations in this guideline**
HTAs (Health Technology Assessments)
No new HTAs since 1 February 2010.
Economic appraisals
No new economic appraisals relevant to England since 1 February 2010.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Wurzel, D., Marchant, J.M., Yerkovich, S.T., et al. (2011) Short courses of antibiotics for children and adults with bronchiectasis (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:
Wong, C., Jayaram, L., Karalus, N., et al. (2012) Azithromycin for the prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 380(9842), 660-667. [Abstract]
Observational studies published since the last revision of this topic:
Chalmers, J.D., McHugh, B.J., Docherty, C., et al. (2013) Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. Thorax 68(1), 39-47. [Abstract]
New policies
No new national policies or guidelines since 1 February 2010.
New safety alerts
No new safety alerts since 1 February 2010.
Changes in product availability
No changes in product availability since 1 February 2010.
Goals and outcome measures
Goals
To support primary healthcare professionals:
To recognize the clinical features of bronchiectasis
To identify and treat exacerbations effectively
To refer appropriately for definitive diagnosis, investigation, and treatment
To promote effective shared-care arrangements with respiratory specialists
QIPP — Options for local implementation
QIPP — Options for local implementation
Antibiotic prescribing — especially quinolones and cephalosporins
Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with Health Protection Agency (HPA) guidance.
Review the total volume of antibiotic prescribing against local and national data.
Review the use of quinolones and cephalosporin prescribing against local and national data.
Background information
Definition
What is it?
Bronchiectasis is a permanent dilatation and thickening of the airways associated with chronic cough, sputum production, bacterial colonization, and recurrent infection.
Focal bronchiectasis is limited to one area of lung.
Diffuse bronchiectasis is widespread.
[Barker, 2002; Rosen, 2006; O'Donnell, 2008; Murray and Hill, 2009]
Causes
What causes it?
Bronchiectasis is caused by chronic inflammation of the airways and is associated with a wide range of diseases.
Inflammation destroys the elastic and muscular components of the bronchi, and the surrounding contractile lung tissue widens the airways.
Mucus collecting in the dilated airways is prone to further infection, resulting in a cycle of recurrent infection and progressive airway injury.
Focal bronchiectasis may be due to:
Bronchial obstruction, such as by a foreign body, tumour, or compression by peri-bronchial lymph nodes.
Prior severe respiratory infection.
Diffuse bronchiectasis may be caused by:
Infection, such as whooping cough, measles, or pneumonia.
Rheumatoid arthritis.
Allergic bronchopulmonary aspergillosis (ABPA).
Immunodeficiency, such as common variable immunodeficiency (hypogammaglobulinaemia) or HIV infection.
Cystic fibrosis.
Primary ciliary dyskinesia.
Inflammatory bowel disease.
Aspiration, for example from gastro-oesophageal reflux.
Yellow nail syndrome.
Other congenital disorders, such as: alpha-1 antitrypsin deficiency; Young's syndrome (characterized by bronchiectasis, rhinosinusitis, and reduced fertility caused by abnormally viscous mucus); and Marfan's syndrome (a genetic disorder of connective tissue).
A UK study of 150 adults with bronchiectasis examined the prevalence of the underlying cause [Pasteur et al, 2000].
No cause or association was found in over 50% of people.
Bronchiectasis followed a childhood chest infection in 30% of people.
Of the rest, 8% were caused by an immune defect, 7% by ABPA, 4% by aspiration, 3% by Young's syndrome, 3% by cystic fibrosis, 3% by rheumatoid arthritis, 1.5% by ciliary dysfunction, and less than 1% by miscellaneous causes.
[Pasteur et al, 2000; DTB, 2003; Rosen, 2006; Shoemark et al, 2007; ten Hacken et al, 2007; Murray and Hill, 2009]
Prevalence
How common is it?
It is estimated that around 1 in 1000 adults in the UK have bronchiectasis [DTB, 2003; ten Hacken et al, 2007].
It may be more common in women than in men, but the evidence for this is limited to a number of case series. Several recent case series found that approximately 70% of people with bronchiectasis were women [King et al, 2006].
Bronchiectasis may be under-diagnosed. A quarter of people diagnosed as having chronic obstructive pulmonary disease by general practitioners may have bronchiectasis [O'Brien et al, 2000; King et al, 2006].
Prognosis
What is the prognosis?
The prognosis for bronchiectasis varies widely. Most people have few or no symptoms and a normal life expectancy. More severe disease results in daily symptoms, progressive loss of lung function, and a reduced life expectancy.
The prognosis has substantially improved with the advent of vaccination programmes and antibiotics.
Before 1940, a third of people with bronchiectasis died before 40 years of age. By the 1960s the average age of death was around 55 years of age.
Clinical experience suggests that the prognosis has continued to improve, although CKS found no evidence to quantify more recent average life expectancy.
The prognosis is worse if the person:
Has extensive disease.
Has frequent exacerbations.
Is colonized by Pseudomonas aeruginosa.
Smokes.
[King et al, 2006, O'Donnell, 2008; Loebinger et al, 2009; British Thoracic Society, 2010]
Complications
What are the complications?
Respiratory complications include:
Repeated infections and chronic bacterial colonization.
Haemoptysis that can occur at any stage of the disease and may be life-threatening.
Pneumothorax or rib fractures secondary to coughing.
Respiratory failure.
Right heart failure, secondary to chronic respiratory disease.
Reduced quality of life caused by:
Anxiety and depression.
Social embarrassment, urinary incontinence, and sexual problems caused by chronic cough.
Chronic tiredness.
Nutritional deficiency, caused by the chronic inflammatory state, breathlessness, and poor appetite.
[Ellis et al, 1981; ten Hacken et al, 2007; McLean, 2008; British Thoracic Society, 2010]
Diagnosis
Diagnosis of bronchiectasis
Detection and diagnosis
When should I suspect bronchiectasis and how do I make the diagnosis?
Suspect bronchiectasis in:
Adults with a chronic cough, particularly in the presence of any of the following:
Daily sputum production.
Pseudomonas aeruginosa in the sputum.
A young age at presentation.
A history of symptoms over many years.
No history of smoking.
Adults thought to have chronic obstructive pulmonary disease, who do not smoke, or who have frequent or prolonged exacerbations.
Children or adults with unexplained haemoptysis (usually recurrent blood-streaked sputum).
Children with a chronic cough (that is usually productive but may be non-productive).
Children thought to have asthma, that responds poorly to treatment.
Identify the clinical features of bronchiectasis.
Exclude other causes for chronic cough based on clinical features and chest radiography.
Refer to a respiratory physician to confirm the diagnosis and determine the underlying cause.
Basis for recommendation
Basis for recommendation
This information is based on expert opinion from the British Thoracic Society [British Thoracic Society, 2010].
Clinical features - children
What are the clinical features of bronchiectasis in children?
There may be a history of:
Failure to thrive.
Recurrent lower respiratory tract infections.
Symptoms of bronchiectasis include:
Chronic cough — usually productive but may be unproductive.
Wheeze.
Haemoptysis (usually blood-streaked sputum).
Exertional breathlessness.
Signs of bronchiectasis include:
Persistent inspiratory crackles.
Finger clubbing, cyanosis, and hyperinflation — these are uncommon in bronchiectasis that is not due to cystic fibrosis.
Signs of malnutrition.
Basis for recommendation
Basis for recommendation
Clinical features of bronchiectasis in children are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Clinical features - adults
What are the clinical features of bronchiectasis in adults?
There may be a history of:
A severe lower respiratory tract infection in early childhood.
Recurrent lower respiratory tract infections.
Symptoms of bronchiectasis include:
Cough — in over 90% of adults.
Cough with daily sputum production — present in over 75% of adults.
Cough with intermittent sputum production — present in up to 20% of adults.
Cough that is unproductive — present in up to 8% of adults.
Breathlessness — present in up to 83% of adults.
Haemoptysis — occurs in up to 50% of adults.
Blood-stained sputum in 27% of adults.
Frank bleeding may occur in up to 20% of adults.
Massive haemoptysis (more than 235 mL) is rarely seen in adults.
Chest pain that is present between exacerbations and is usually non-pleuritic — present in 31% of adults.
Signs of bronchiectasis include:
Course crackles during early inspiration that are commonest in the lower lung fields — present in approximately 70% of adults.
Wheeze — present in 34% of people.
Large airway rhonchi (low pitched snore-like sounds) — present in 44% of adults.
Finger clubbing — occurs very infrequently.
Basis for recommendation
Basis for recommendation
The prevalence of the clinical features of bronchiectasis in adults is based on evidence summarized by the British Thoracic Society [British Thoracic Society, 2010].
Other causes of chronic cough
What other causes of chronic cough should I consider?
Chronic cough is a characteristic feature of many disorders, many of which are more common than bronchiectasis.
Common causes of chronic cough include:
Smoking.
Asthma.
Chronic obstructive pulmonary disease.
Drug adverse effects (for example angiotensin converting enzyme inhibitors).
Upper airway cough syndrome (previously known as postnasal drip syndrome).
Gastro-oesophageal reflux disease.
Less common but serious causes of chronic cough include:
Lung cancer.
Pulmonary fibrosis.
Tuberculosis.
Foreign body.
Basis for recommendation
Basis for recommendation
The differential diagnosis is based on expert opinion in review articles and a text book [Lane, 2003; Rosen, 2006; Chung and Pavord, 2008].
Primary care investigations
What investigations should be undertaken in primary care for a person with suspected bronchiectasis?
Arrange chest X-ray in all people suspected of having bronchiectasis.
The chest X-ray is abnormal in 90% of people with bronchiectasis; however, radiological findings are not usually diagnostic.
The main value of chest X-ray is to exclude other causes of chronic cough (such as lung cancer).
Consider further investigations to exclude other causes of chronic cough, guided by clinical findings.
Refer to a respiratory physician to confirm the diagnosis and determine the underlying cause of bronchiectasis.
Basis for recommendation
Basis for recommendation
The recommendation for chest X-ray in all people with suspected bronchiectasis is based on expert opinion [Barker, 2002; Rosen, 2006; ten Hacken et al, 2007; O'Donnell, 2008; British Thoracic Society, 2010]. There is expert consensus:
That chest X-rays lack sensitivity and specificity for the diagnosis of bronchiectasis.
The main role is to exclude other causes for symptoms in people suspected of having bronchiectasis.
Secondary care investigations
How is bronchiectasis confirmed and the underlying cause determined in secondary care?
High-resolution computed tomography (HRCT) scanning is the investigation of choice to establish the diagnosis of bronchiectasis.
Investigations to determine the underlying cause of bronchiectasis include:
Further testing for cystic fibrosis — such as sweat chloride or gene testing for all children and adults up to 40 years of age and adults older than 40 years of age with clinical features consistent with cystic fibrosis.
Screening for gross antibody deficiency — serum IgG (immunoglobulin G), IgA, IgM and electrophoresis for all people with confirmed bronchiectasis.
Investigation of immunological disorders — such as alpha-1 antitrypsin level, serum IgE, Aspergillus-specific IgE and precipitins; for people with clinical features or risk factors for immunological disorders.
Bronchoscopy may be indicated for further investigation of lower respiratory tract infection or bronchial obstruction (for example for suspected foreign body aspiration in children or to exclude an endobronchial lesion in adults).
Gastrointestinal investigations such as 24-hour pH monitoring for people suspected of having bronchiectasis secondary to gastro-oesophageal reflux and aspiration.
Basis for recommendation
Basis for recommendation
Investigations to make a diagnosis of bronchiectasis
The recommendation for a high-resolution CT scan to establish the diagnosis of bronchiectasis is based on evidence of [Grenier et al, 1986]:
A specificity and sensitivity of over 90% when compared with the prior gold standard of bronchography.
A lower risk of adverse effects compared with bronchography.
Investigations to determine the underlying cause of bronchiectasis
Recommended investigation of the underlying cause of bronchiectasis is based on expert opinion from the British Thoracic Society [British Thoracic Society, 2010].
Management
Management
Scenario : Infective exacerbation: covers the management of an infective exacerbation of bronchiectasis.
Scenario : Chronic disease management: covers the long-term management of bronchiectasis.
Scenario : Infective exacerbation
Scenario : Infective exacerbation of bronchiectasis
Diagnosing infective exacerbation
How do I know my patient has an infective exacerbation of bronchiectasis?
Diagnose an infective exacerbation of bronchiectasis requiring antibiotic therapy when there is:
Acute deterioration (usually over several days), with worsening cough (with increased sputum volume, viscosity, or purulence; with or without increasing wheeze, breathlessness, or haemoptysis) and/or systemic upset.
The presence of mucopurulent or purulent sputum alone, or the isolation of a pathogen alone, without a deterioration in symptoms is not necessarily an indication for antibiotic treatment, particularly in adults.
Basis for recommendation
Basis for recommendation
Diagnostic criteria for infective exacerbations of bronchiectasis are based on expert opinion from the British Thoracic Society [British Thoracic Society, 2010].
When to admit
When should I admit someone with an acute exacerbation?
Arrange hospital admission for adults who:
Are unable to cope at home.
Are cyanosed or confused.
Have a respiratory rate more than 25 breaths per minute.
Have signs of cardiorespiratory failure (such as marked breathlessness, rapid respiration, laboured breathing, cyanosis, worsening peripheral oedema, or oxygen saturation < 93% on room air).
Have a temperature of 38°C or more.
Are unable to take oral therapy.
Have failed to respond adequately to oral therapy.
Have pleuritic pain severe enough to inhibit coughing and the clearing of secretions.
Arrange hospital admission for children who:
Are cyanosed.
Have increased respiratory rate and work of breathing.
Have signs of cardiorespiratory failure (such as marked breathlessness, rapid respiration, laboured breathing, cyanosis, worsening peripheral oedema, or oxygen saturation < 93% on room air).
Have a temperature of 38°C or more.
Are unable to take oral therapy.
Fail to respond adequately to oral therapy.
Basis for recommendation
Basis for recommendation
Admission criteria for people with an infective exacerbation of bronchiectasis are based on expert opinion from the British Thoracic Society [British Thoracic Society, 2010] and (in the case of pleuritic complications) a CKS expert reviewer.
Management in primary care
How do I manage an infective exacerbation of bronchiectasis in primary care?
Send sputum for culture and sensitivity testing before starting antibiotics (even if the person is taking long-term antibiotics).
Collect expectorated sputum after deep coughing. A pharyngeal swab after coughing may be of value in very young children.
Ensure prompt transport of specimens to the laboratory, as Haemophilus influenzae and Streptococcus pneumoniae may only be viable if the specimen is processed within 3 hours.
Promptly prescribe an antibiotic for 10–14 days.
Do not await the results of culture.
For further information, see Antibiotic choice.
Prescribe a short-acting inhaled beta2-agonist (such as salbutamol) if necessary for wheeze or breathlessness in the acute phase.
Avoid using inhaled or oral corticosteroids, unless required for the treatment of coexisting asthma or chronic obstructive pulmonary disease.
Ensure that a suitable airway clearance technique (that has been taught by a respiratory physiotherapist) is used during the exacerbation.
Arrange an urgent appointment with a physiotherapist if the person has not already been taught this or if they cannot manage this alone.
Review the response to empirical treatment when sputum culture and sensitivity results are available.
If the person is responding well, continue with the prescribed antibiotic. Do not change the treatment based on the culture results.
If the person has not responded well to treatment, prescribe a different antibiotic. The choice of antibiotic should be guided by the results of sputum culture and sensitivity testing.
If the person deteriorates at any stage after starting treatment, re-assess to see if hospital admission is indicated.
Basis for recommendation
Basis for recommendation
Sputum culture
Experts recommend that samples should be collected even in people taking long-term antibiotics, as the antibiotic doses used are low and have little effect on actual pathogens isolated [McLean, 2008].
Antibiotics
Recommendations on the use of antibiotics are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010] and the opinions of CKS expert reviewers, who also recommend some flexibility in the duration of antibiotic treatment. Not all people may require the full 14 days. Clinical judgement is advised due to the weakness of the evidence base.
The recommendation to not switch antibiotic on the basis of culture results unless there also is a lack of clinical response is based on expert opinion. This is because some people may respond to antibiotic treatment despite resistance to that drug in vitro [Murray and Hill, 2009; British Thoracic Society, 2010].
Inhaled short-acting beta2-agonist
CKS expert reviewers advise that while a short-acting beta2-agonist may be prescribed for acute symptoms, longer-term use should prompt secondary care referral for review.
Corticosteroids
CKS expert reviewers advised that inhaled or oral corticosteroids have no routine role for the treatment of isolated bronchiectasis; but they may be of value for the treatment of coexisting conditions such as asthma.
Physiotherapy
It is not possible, from the limited available evidence, to assess the effectiveness of physiotherapy for people with bronchiectasis.
It is widely believed by experts that airway clearance techniques are an important component of managing bronchiectasis [British Thoracic Society, 2010].
Antibiotic choice
Which antibiotic should I prescribe for an infective exacerbation of bronchiectasis?
Previous microbiology cultures, when available, should guide antibiotic choice.
For more information, see Table 1.
When previous microbiology cultures are not available:
Prescribe according to local protocols where available, or
Prescribe amoxicillin 500 mg three times a day (for 10–14 days). Clarithromycin 500 mg twice a day, erythromycin 500 mg four times a day, or doxycycline (adults only) 200 mg stat and then 100 mg once a day (all for 10–14 days) are alternatives for people allergic to penicillin.
For further information on dosing regimens for empirical antibiotic treatment, see Prescriptions.
Table 1. Recommended antibiotics (with doses for adults) for acute exacerbations of bronchiectasis if sputum results from a previous sputum sample are available.| Organism | First-line antibiotic | Second-line antibiotic | Duration |
|---|---|---|---|
| Streptococcus pneumoniae | Amoxicillin 500 mg TDS | Clarithromycin 500 mg BD | 10–14 days |
| Haemophilus influenzae (beta-lactamase negative) | Amoxicillin 500 mg TDS orAmoxicillin 1 g TDS orAmoxicillin 3 g BD | Clarithromycin 500 mg BDorDoxycycline 200 mg stat, then 100 mg OD* | 10–14 days |
| Haemophilus influenzae (beta-lactamase positive) | Co-amoxiclav 625 mg TDS | Clarithromycin 500 mg BDorDoxycycline 200 mg stat, then 100 mg OD* | 10–14 days |
| Moraxella catarrhalis | Co-amoxiclav 625 mg TDS | Doxycycline 200 mg stat, then 100 mg OD* | 10–14 days |
| Staphylococcus aureus (MSSA) | Flucloxacillin 500 mg QDS | Clarithromycin 500 mg BD | 10–14 days |
| Staphylococcus aureus (MRSA) | Rifampicin‡ PLUS trimethoprim 200 mg BD | Rifampicin PLUS doxycycline 100 mg BD‡§ | 10–14 days |
| Coliforms (such as Klebsiella or enterobacter) | Ciprofloxacin 500 mg BD | Intravenous antibiotics | 10–14 days |
| Pseudomonas aeruginosa | Ciprofloxacin 500 mg BD†orCiprofloxacin 750 mg BD | Intravenous antibiotics | 10–14 days |
Basis for recommendation
Basis for recommendation
Recommendations on the use of antibiotics are largely based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Choice of antibiotic
Recommended antibiotics reflect the likely pathogens. The commonest bacteria isolated during infective exacerbations of bronchiectasis include Haemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus (the presence of which raises the suspicion of cystic fibrosis), and mycobacterium. Sometimes no organism is found [O'Donnell, 2008].
Amoxicillin is a reasonable first-line empirical choice in the absence of previous sputum results as it has good activity against H. influenzae and S. pneumoniae [Murray and Hill, 2009; British Thoracic Society, 2010]. In addition, it is usually well tolerated and is inexpensive.
Clarithromycin and erythromycin are recommended as alternatives for people with penicillin allergy [Murray and Hill, 2009; British Thoracic Society, 2010]. They are active against H. influenzae, S. pneumoniae, S. aureus (meticillin sensitive) and M. catarrhalis. However, resistance to H. influenzae is increasing [Bryskier and Butzler, 2003].
Clarithromycin causes fewer gastrointestinal adverse effects than erythromycin [DTB, 1991], and adherence may be easier because of the twice-daily regimen.
Erythromycin is less expensive than clarithromycin, particularly for the suspension formulations [Prescription Pricing Division, 2010]. It is the macrolide of choice in women who are pregnant or breastfeeding [Trent Drug Information Service, 2001; NTIS, 2008b].
Doxycycline is an alternative empirical antibiotic for people with penicillin allergy [HPA, Personal Communication, 2010]. It is active against H. influenzae, S. pneumoniae, S. aureus and M. catarrhalis. It is available as a convenient, once-daily regimen (after an initial loading dose), is well tolerated by most people, and is relatively inexpensive.
Duration of antibiotic treatment
The duration of treatment is based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010] and the opinions of CKS expert reviewers, who also recommend some flexibility in the duration of antibiotic treatment. Not all people may require the full 14 days. Clinical judgement is advised due to the weakness of the evidence base.
Scenario : Chronic disease management
Scenario : Chronic disease management of bronchiectasis
Primary care follow-up
What follow-up is recommended for people with bronchiectasis in primary care?
All children with bronchiectasis should be followed up by a specialist.
All adults with bronchiectasis should be offered an annual review in primary care. Ask about:
Smoking.
The number of exacerbations in the last year.
Breathlessness associated with activities of daily living.
Sputum volume and character.
Send sputum for culture and sensitivity at annual review or if it has become persistently purulent between exacerbations — to assess for chronic bacterial colonization.
Specialist follow up is required for adults with:
Chronic colonization with Pseudomonas aeruginosa, opportunist mycobacteria, or meticillin-resistant Staphylococcus aureus (MRSA).
Deteriorating symptoms.
Three or more infective exacerbations a year.
Bronchiectasis requiring long-term prophylactic antibiotics.
Bronchiectasis associated with rheumatoid arthritis, immune deficiency, inflammatory bowel disease, primary ciliary dyskinesia, and allergic bronchopulmonary aspergillosis.
Advanced disease.
Ensure all people with bronchiectasis:
Know how to recognize exacerbations and understand the condition. A patient information leaflet on bronchiectasis is available from the British Lung Foundation.
Have a record of sputum cultures from previous exacerbations to guide future treatment of exacerbations.
Have been taught an airway clearance technique by a physiotherapist — for daily use by people with a chronic productive cough, and intermittent use by people with a productive cough during exacerbations.
Offer pulmonary rehabilitation to people with bronchiectasis and breathlessness associated with activities of daily living.
Refer the person to a specialist to arrange this.
People who have been advised to start antibiotics themselves for exacerbations should:
Understand when it is appropriate to start treatment and the importance of collecting sputum before starting treatment.
Have sputum collection pots and a repeat prescription for antibiotics.
Offer immunization against Streptococcus pneumoniae and seasonal influenza. See CKS topics on Immunizations - pneumococcal and Immunizations - seasonal influenza.
Offer people who smoke advice and support to help them stop — for further information, see the CKS topic on Smoking cessation.
Do not routinely repeat chest X-rays.
Routine annual spirometry is not recommended for people who are stable, with minimal exercise limitation, and who have few exacerbations.
Basis for recommendation
Basis for recommendation
Recommendations on who should receive follow up in secondary care
These recommendations are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Record of sputum cultures from previous exacerbations
Experts consider that treatment of exacerbations is more likely to be effective when this is based on previous sputum culture results [British Thoracic Society, 2010].
The recommendation to send sputum samples for analysis at annual review, when the person is clinically stable, is based on the opinion of a CKS expert reviewer.
Physiotherapy
It is not possible, from the limited available evidence, to assess the effectiveness of physiotherapy for people with bronchiectasis.
It is widely believed by experts that airway clearance techniques are an important component of managing bronchiectasis [British Thoracic Society, 2010].
Pulmonary rehabilitation
Pulmonary rehabilitation is recommended for people with bronchiectasis associated with exercise limitation. This is based on limited evidence summarized by the British Thoracic Society [British Thoracic Society, 2010].
A Cochrane systematic review showed that inspiratory muscle training improved exercise endurance and health-related quality of life [Bradley et al, 2002].
Further evidence from a randomized controlled trial compared exercise capacity in three groups of people. The first group received 8 weeks of a high intensity pulmonary rehabilitation programme with inspiratory muscle training; the second group received pulmonary rehabilitation with sham inspiratory muscle training; and a control group received no rehabilitation.
There was a statistically significant improvement in exercise capacity in both groups receiving pulmonary rehabilitation.
This improvement was maintained in the group receiving additional inspiratory muscle training but not in the group that received sham inspiratory muscle training.
Immunization
There is a lack of evidence on the benefit of vaccination in people with bronchiectasis [ten Hacken et al, 2007]. The recommendation to offer people with bronchiectasis immunization against seasonal influenza and Streptococcus pneumoniae is based on expert opinion from the British Thoracic Society [British Thoracic Society, 2010].
Smoking cessation advice
Recommendations on smoking cessation advice are based on accepted good clinical practice.
Secondary care follow-up
Who should be followed-up in secondary care?
Regular follow up in secondary care is recommended for:
All children.
Adults with bronchiectasis, with:
Chronic colonization with Pseudomonas aeruginosa, opportunist mycobacteria, or meticillin-resistant Staphylococcus aureus (MRSA).
Clinical deterioration with declining lung function.
Three or more infective exacerbations a year.
Requirement for long-term prophylactic antibiotics.
Co-existing rheumatoid arthritis, immune deficiency, inflammatory bowel disease, primary ciliary dyskinesia, or allergic bronchopulmonary aspergillosis.
Advanced disease — including those people who are being considered for transplantation.
Secondary care follow up for adults with less severe disease is at the discretion of the specialist.
Follow up is likely to be exclusively in primary care if the disease is stable, with minimal exercise limitation and few exacerbations.
Follow up is usually shared between primary care and secondary care for people with intermediate disease severity.
Basis for recommendation
Basis for recommendation
Recommendations on who should receive follow up in secondary care are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Secondary care management
What treatments for bronchiectasis may be initiated in secondary care?
All people with bronchiectasis should be referred to a respiratory physiotherapist for the teaching of an airway clearance technique.
People with a chronic productive cough should use the technique every day.
People who have a productive cough during exacerbations can use the technique intermittently (during an exacerbation).
All people with bronchiectasis who have breathlessness associated with activities of daily living should be offered pulmonary rehabilitation.
All people having three or more exacerbations a year, and those with fewer exacerbations causing significant morbidity, should be considered for long-term prophylactic treatment with antibiotics.
Nebulized antibiotics should be considered in adults chronically colonized with Pseudomonas aeruginosa.
Nebulized antibiotics should be considered in children with frequent recurrent exacerbations, or deteriorating bronchiectasis despite oral antibiotics, or if oral antibiotics are not appropriate.
Long-term treatment with theophylline, aminophylline, inhaled beta2-agonists, or inhaled anticholinergic bronchodilators should only be prescribed after a trial of therapy has demonstrated improvement of symptoms or lung function.
Lung resection surgery may be considered in people with localized disease when symptoms cannot be controlled by medical treatment.
Basis for recommendation
Basis for recommendation
Physiotherapy
It is not possible, from the limited available evidence, to assess the effectiveness of physiotherapy for people with bronchiectasis.
It is widely believed by experts that airway clearance techniques are an important component of managing bronchiectasis [British Thoracic Society, 2010].
Pulmonary rehabilitation
UK Guidelines recommend a number of techniques; such as postural drainage and pelvic floor muscle training [Bott et al, 2009].
Pulmonary rehabilitation is recommended in individuals with bronchiectasis who are breathless during activities of daily living; based on limited evidence summarized by the British Thoracic Society [British Thoracic Society, 2010].
A Cochrane systematic review showed that inspiratory muscle training improved exercise endurance and health-related quality of life [Bradley et al, 2002].
Further evidence was provided from a randomized controlled trial that compared exercise capacity in three groups of people. The first group received 8 weeks of a high intensity pulmonary rehabilitation programme with inspiratory muscle training; the second group received pulmonary rehabilitation with sham inspiratory muscle training; and a control group received no rehabilitation.
There was a statistically significant improvement in exercise capacity in both groups receiving pulmonary rehabilitation.
This improvement was maintained in the group receiving additional inspiratory muscle training but not in the group that received sham inspiratory muscle training.
Prophylactic antibiotics
Limited evidence from studies of long-term antibiotics suggest small clinical benefits, and no benefit in terms of exacerbation rate or lung function.
Information on who should receive long-term antibiotics are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Bronchodilators
Information on the use of bronchodilators are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
It is unclear from the limited available evidence whether bronchodilators are beneficial in bronchiectasis.
Lung resection surgery
Information on lung resection surgery are based on the expert opinion of the British Thoracic Society [British Thoracic Society, 2010].
Treatments not recommended
What treatments are not recommended for bronchiectasis?
These treatments should not be used for the treatment of bronchiectasis:
Corticosteroids (inhaled or oral) — unless there is coexistent asthma.
Mucolytics.
Leukotriene receptor antagonists.
Basis for recommendation
Basis for recommendation
Mucolytics
There is insufficient evidence to determine whether mucolytics are of benefit for people with bronchiectasis.
Experts recommend that these should not be routinely prescribed for the treatment of bronchiectasis [British Thoracic Society, 2010].
Inhaled corticosteroids
There is insufficient evidence to determine whether inhaled corticosteroids are of benefit for people with bronchiectasis.
Experts recommend that these should not be routinely prescribed for the treatment of bronchiectasis (unless there is coexistent asthma) [British Thoracic Society, 2010].
Oral corticosteroids
There is insufficient evidence to determine whether oral corticosteroids are of benefit for people with bronchiectasis.
Experts recommend that these should not be routinely prescribed for the treatment of bronchiectasis [British Thoracic Society, 2010].
Leukotriene receptor antagonists
There is insufficient evidence to determine whether leukotriene receptor antagonists are of benefit for people with bronchiectasis.
Experts recommend that these should not be routinely prescribed for the treatment of bronchiectasis [British Thoracic Society, 2010].
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).
Amoxicillin
Amoxicillin
Amoxicillin is usually well tolerated; but nausea, vomiting, or diarrhoea can sometimes occur.
Advise people taking penicillin antibiotics to seek urgent medical advice if they get a rash, swelling of the face, hands or feet, or feel short of breath (as this may indicate an allergic response).
Additional contraceptive precautions are not required during or after a course of amoxicillin.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
Basis for recommendation
These recommendations are based on information from the manufacturer [ABPI Medicines Compendium, 2010], Stockley's drug interactions [Baxter, 2008], and the Faculty of Sexual and Reproductive Healthcare [FSRH, 2011]. In particular:
Although the UKMEC criteria advise additional precautions with antibiotics that do not induce enzymes [FSRH, 2009], this was an interim measure until the evidence could be reviewed in detail by the FSRH clinical effectiveness unit [FSRH, 2011].
Having reviewed the available evidence, the FSRH no longer advises that additional precautions are required to maintain contraceptive efficacy when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less, unless the antibiotics (or the illness) cause vomiting or diarrhoea [FSRH, 2011].
Clarithromycin and erythromycin
Clarithromycin and erythromycin
Clarithromycin is better tolerated than erythromycin, but nausea, vomiting, or diarrhoea can sometimes occur.
Clarithromycin and erythromycin should be used with caution in people with:
Severe renal impairment
If the estimated glomerular filtration rate (eGFR) is less than 30 mL/minute/1.73 m2 — use half the clarithromycin dose (that is, reduce it from 500 mg twice daily to 250 mg twice daily).
If the eGFR is less than 15 mL/minute/1.73 m2 — use a maximum of erythromycin 1.5 g per day (since there is a risk of ototoxicity).
Liver disease — consider avoiding clarithromycin and erythromycin, as they can cause hepatic dysfunction. Hepatic failure has been reported with clarithromycin, very rarely, in people with liver disease.
Consider the possibility of drug interactions before prescribing clarithromycin or erythromycin in people taking:
Aminophylline or theophylline — check theophylline levels 48 hours after starting erythromycin and adjust the dose accordingly. Interaction is less likely with clarithromycin unless theophylline levels are at the higher end of the therapeutic range.
Carbamazepine — use azithromycin instead (interaction unlikely) or consider reducing the dose of carbamazepine by 30–50% during treatment with clarithromycin and advise the person to report symptoms of toxicity (such as dizziness, diplopia, ataxia, confusion). Clarithromycin and erythromycin inhibit cytochrome P450 enzyme CYP3A4, resulting in reduced carbamazepine metabolism.
Warfarin — this is an established but unpredictable interaction. Monitor the international normalized ratio (INR) and adjust the warfarin dose accordingly.
Atorvastatin or simvastatin — use azithromycin instead, but advise the person to report muscle symptoms (interaction unlikely). Alternatively, stop atorvastatin or simvastatin for the duration of treatment with clarithromycin or erythromycin (inhibits metabolism of atorvastatin and simvastatin via CYP3A4).
Drugs that prolong the QT interval (such as antiarrhythmics, antipsychotics, tricyclic antidepressants) — seek advice from a microbiologist regarding a suitable alternative antibiotic. All macrolides can prolong the QT interval. Concomitant use of two drugs that prolong the QT interval is not recommended.
Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta2-agonists) — hypokalaemia is a risk factor for QT prolongation.
Contraceptives — additional contraceptive precautions are not required during or after a course of clarithromycin or erythromycin.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
Basis for recommendation
These recommendations are based on information from Stockley's drug interactions [Baxter, 2008], the Medicines and Healthcare Regulatory Agency (MHRA) [CSM, 1996; CSM, 2004; MHRA, 2008], the Faculty of Sexual and Reproductive Healthcare [FSRH, 2011], and the Drug and therapeutics bulletin [DTB, 1991]. In particular:
Although the UKMEC criteria advise additional precautions with antibiotics that do not induce enzymes [FSRH, 2009], this was an interim measure until the evidence could be reviewed in detail by the FSRH clinical effectiveness unit [FSRH, 2011].
Having reviewed the available evidence, the FSRH no longer advises that additional precautions are required to maintain contraceptive efficacy when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less, unless the antibiotics (or the illness) cause vomiting or diarrhoea [FSRH, 2011].
Doxycycline
Doxycycline
Do not use doxycycline in:
Children under the age of 12 years — tetracyclines are deposited in the teeth (causing staining) and bones of the developing child.
Pregnant or breast feeding women.
If possible, avoid doxycycline in:
People with hepatic impairment or alcohol dependence — hepatic excretion.
People travelling to a hot country or people who use sunlamps — doxycycline can cause photosensitivity reactions.
Doxycycline can sometimes cause gastrointestinal adverse effects (e.g. nausea, vomiting, diarrhoea, oesophageal irritation).
Advise people taking doxycycline to:
Take the capsules with food or milk to help prevent gastrointestinal adverse effects. The capsules should be swallowed whole with plenty of fluids while sitting or standing (to prevent oesophageal irritation).
Avoid exposure to direct sunlight or to sunlamps.
Avoid taking indigestion remedies (e.g. antacids), or medicines containing iron or zinc at the same time as doxycycline — they should be taken 2–3 hours apart.
Contraceptives — additional contraceptive precautions are not required during or after a course of doxycyline.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
Warfarin — the effects of warfarin are not usually altered to a clinically relevant extent by treatment with a tetracycline. However, a few patients have unpredictably shown increased anticoagulant effects. Advise people taking warfarin to report any unusual bruising or bleeding whilst taking doxycycline.
Benign intracranial hypertension is a rare but important adverse effect of tetracyclines. If a person taking doxycycline develops headache and visual disturbances, it should be stopped.
Basis for recommendation
These recommendations are based on information from the manufacturer's Summary of Product Characteristics [ABPI Medicines Compendium, 2008]. In addition:
The information regarding drug interactions with antacids is taken from the British national formulary [BNF 59, 2010].
The information regarding drug interactions with warfarin is taken from Stockley's drug interactions [Baxter, 2008].
Although the UKMEC criteria advise additional precautions with antibiotics that do not induce enzymes [FSRH, 2009], this was an interim measure until the evidence could be reviewed in detail by the FSRH clinical effectiveness unit [FSRH, 2011].
Having reviewed the available evidence, the FSRH no longer advises that additional precautions are required to maintain contraceptive efficacy when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less, unless the antibiotics (or the illness) cause vomiting or diarrhoea [FSRH, 2011].
Antibiotics in pregnancy and breastfeeding
Antibiotic choice in pregnancy and breastfeeding
Pregnancy
Antibiotics that can be used by women who are pregnant, for an exacerbation of bronchiectasis, include:
Penicillins (such as amoxicillin, co-amoxiclav, flucloxacillin).
Erythromycin.
Antibiotics which should not be used during pregnancy, include:
Clarithromycin.
Ciprofloxacin.
Doxycycline.
Breastfeeding
Antibiotics that can be used by women who are breastfeeding, for an exacerbation or bronchiectasis, include:
Penicillins (such as amoxicillin, co-amoxiclav, flucloxacillin).
Erythromycin (but avoid if the neonate is jaundiced).
Antibiotics that may be used by women who are breastfeeding, if the benefits are thought to outweigh the risks, include:
Clarithromycin (off-label use; avoid if the neonate is jaundiced).
Ciprofloxacin (off-label use).
Doxycycline should not be used during breastfeeding.
Basis for recommendation
Penicillins
The available data on the use of penicillins in pregnancy do not suggest they are associated with an increased risk of congenital abnormalities above the background rate for the population [NTIS, 2008b].
Only low levels of penicillins are found in breast milk and their use during breastfeeding is well established [Trent Drug Information Service, 2001].
Erythromycin
Data from more than 7000 pregnancies do not indicate that erythromycin is associated with an increased risk of congenital malformations and other adverse fetal effects. A recent study suggested a possible increased risk of cardiovascular malformation and pyloric stenosis; however causality has not been established and the individual risk, if any, is thought to be low [NTIS, 2008a].
Only low levels of erythromycin are found in breast milk and its use during breastfeeding is well established [NPIS, 2010a]. However, erythromycin should be avoided if the neonate has jaundice. There are case reports of pyloric stenosis in breastfed neonates of women who were taking erythromycin, but causality has not been established [Schaefer et al, 2007].
Clarithromycin
There are fewer data available on pregnancy outcomes with clarithromycin than erythromycin, therefore erythromycin is preferred if a macrolide is required during pregnancy. One study reported an increased risk of spontaneous abortion in utero, but this finding has not been replicated [NTIS, 2008c].
Use of clarithromycin is less well established than use of erythromycin in breastfeeding, although the available data suggest that only low levels are found in breast milk [Trent Drug Information Service, 2001; NPIS, 2009].
Ciprofloxacin
There are limited data available on quinolones in human pregnancy. Due to these limited data and the theoretical risk of arthropathy in the infant (extrapolated from animal studies), the use of quinolones in pregnancy is not generally recommended (except for the treatment of serious of life-threatening conditions unresponsive to standard antibiotic therapy) [NTIS, 2008b].
Ciprofloxacin is excreted into breast milk but in only low levels that are not thought to be harmful (theoretical risk of arthropathy in the infant). It is possible that the calcium in breast milk could prevent the infant absorbing the ciprofloxacin, since ciprofloxacin is known to chelate with metal ions, but there are no data to prove or disprove this theory [NPIS, 2010b].
Doxycycline
Due to the risk of its deposition in developing bones and teeth, doxycyline should not be given to women who are pregnant or breastfeeding [ABPI Medicines Compendium, 2008; NTIS, 2008b]. However, it is possible that the risk in breastfeeding is reduced because calcium in breast milk is likely to chelate the doxycycline and prevent absorption [NPIS, 2010c].
Short-acting beta2-agonists
Short-acting beta2-agonists
Inhaled short-acting beta2-agonists should be used as required unless an individual has shown to benefit from regular use.
Inhaled short-acting beta2-agonists have minimal adverse effects. However:
Overuse can cause tremor, tension, headache, muscle cramps, and palpitations.
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.
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.
Basis for recommendation
The recommendation to use beta2-agonists as required is extrapolated from the SIGN and BTS guideline, British guideline on the management of asthma [SIGN and BTS, 2008].
The information on adverse effects is based on the manufacturer's Summary of Product Characteristics [ABPI Medicines Compendium, 2007] and advice from the Medicines and Healthcare products Regulatory Agency [MHRA, 2007] and the Committee on Safety of Medicines [CSM, 1990].
Evidence
Evidence
Supporting evidence
The evidence on treatments that could potentially be initiated in primary care has been reviewed and summarized in this section.
Vaccinations
Evidence on vaccinations in people with bronchiectasis
CKS found no randomized controlled trials evaluating the efficacy of influenza vaccine or pneumococcal vaccine for people with bronchiectasis.
Influenza vaccine
One Cochrane systematic review (search date: to July 2006) found no randomized controlled trials evaluating the efficacy of influenza vaccines for people with confirmed bronchiectasis [Chang et al, 2007]. Studies evaluating people with cystic fibrosis were excluded.
Pneumococcal vaccine
One Cochrane systematic review (search date: to July 2006) found no randomized controlled trials evaluating the efficacy of pneumococcal vaccines for people with confirmed bronchiectasis [Chang et al, 2009]. Studies evaluating people with cystic fibrosis were excluded.
Bronchodilators
Evidence on bronchodilators for bronchiectasis
It is unknown whether bronchodilators are beneficial for bronchiectasis. CKS found no randomized controlled trials evaluating the efficacy of inhaled short-acting beta2-agonists, inhaled long-acting beta2-agonists, inhaled anticholinergics, oral methylxanthines, or oral leukotriene-receptor antagonists.
Short-acting beta2-agonists
One Cochrane systematic review (search date: to May 2008) found no randomized controlled trials evaluating the efficacy of inhaled short-acting beta2-agonists in people with confirmed bronchiectasis [Franco et al, 2003]. Studies evaluating people with cystic fibrosis were excluded.
Long-acting beta2-agonists
One Cochrane systematic review (search date: to August 2008) found no randomized controlled trials evaluating the efficacy of inhaled long-acting beta2-agonists in people with confirmed bronchiectasis [Sheikh et al, 2001]. Studies evaluating people with cystic fibrosis were excluded.
Anticholinergics
One Cochrane systematic review (search date: to May 2005) found no randomized controlled trials evaluating the efficacy of inhaled anticholinergics in people with confirmed bronchiectasis [Lasserson et al, 2001a]. Studies evaluating people with cystic fibrosis were excluded.
Methylxanthines
One Cochrane systematic review (search date: to July 2008) found no randomized controlled trials evaluating the efficacy of oral methylxanthines in people with confirmed bronchiectasis [Steele and Greenstone, 2000]. Studies evaluating people with cystic fibrosis were excluded.
Leukotriene-receptor antagonists
One Cochrane systematic review (search date: to April 2009) found no randomized controlled trials evaluating the efficacy of oral leukotriene-receptor antagonists in people with confirmed bronchiectasis [Corless and Warburton, 2000]. Studies evaluating people with cystic fibrosis were excluded.
Inhaled corticosteroids
Evidence on inhaled corticosteroids for bronchiectasis
CKS found inadequate evidence to recommend the routine use of inhaled corticosteroids in adults with stable bronchiectasis. Only marginal benefits were found in trials using high-dose inhaled corticosteroids.
One Cochrane systematic review of inhaled corticosteroids for bronchiectasis (search date: to September 2007) identified six small randomized controlled trials (RCTs) that fulfilled the inclusion criteria (303 participants) [Kapur et al, 2009]. All studies were conducted in adults with stable bronchiectasis that had been diagnosed by bronchography or high resolution computed tomography (CT) of the chest. Studies evaluating people with cystic fibrosis were excluded.
Quality of the included studies
All studies were randomized but allocation concealment was unclear. Five studies were double-blind and placebo-controlled; one was a dose-ranging study. Sample size was generally small, varying from 20 to 93 participants. There was no heterogeneity between studies.
Short-term efficacy (6 months or less)
Pooled data from three RCTs (101 participants) showed a small improvement in mean FEV1 (forced expiratory volume in the first second) in those taking inhaled corticosteroids compared with placebo (fixed mean difference 0.09, 95% CI 0.003 to 0.15). There was also a small improvement in mean FVC (forced vital capacity) in those taking inhaled corticosteroids compared with placebo (fixed mean difference 0.09, 95% CI 0.02 to 0.16). However, if the study without a placebo control was excluded, the trend was not significant.
Pooled data from two RCTs (44 participants) showed a trend towards improved peak flow volumes with inhaled corticosteroids (fixed mean difference 26.23, 95% CI –5.84 to +58.31) but this was not statistically significant.
Data on exacerbations were only available from one study (93 participants) which showed no difference between groups (fixed mean difference 0.09, 95% CI –0.71 to +0.79).
Long-term efficacy (more than 6 months)
Data were only available from one study (86 participants) which found no significant difference between inhaled corticosteroids and placebo for FEV1, FVC, or exacerbations.
Harms
Harms were not reported in this meta-analysis.
However, high daily doses of inhaled corticosteroids were used: most studies used fluticasone 1000 micrograms per day, one used beclometasone 1500 micrograms per day, and one used beclometasone 800 micrograms per day.
Authors' conclusions
The authors concluded that there is insufficient evidence to recommend the routine use of inhaled corticosteroids in adults with stable state bronchiectasis. If a therapeutic trial is being considered in adults with difficult to control symptoms, this must be balanced against the adverse effects, especially if high doses are used.
Oral corticosteroids
Evidence on oral corticosteroids for bronchiectasis
It is not known whether oral corticosteroids are beneficial for bronchiectasis. CKS found no randomized controlled trials evaluating their efficacy.
One Cochrane systematic review (search date: to May 2007) found no randomized controlled trials evaluating the efficacy of oral corticosteroids in people with confirmed bronchiectasis [Lasserson et al, 2001b]. Studies evaluating people with cystic fibrosis were excluded.
Mucolytics
Evidence on mucolytics for bronchiectasis
CKS found inadequate evidence to determine whether mucolytics are of use in bronchiectasis. The available evidence suggests that nebulized recombinant human DNase may worsen lung function. Oral bromhexine and inhaled mannitol are not available in the UK.
One Cochrane systematic review of mucolytics for bronchiectasis (search date: to January 2008) identified three small randomized controlled trials (RCTs) that fulfilled the inclusion criteria [Crockett et al, 2001]. Studies evaluating people with cystic fibrosis were excluded.
Quality of the included studies
All studies were randomized and double-blind, but methodological quality was poor. Sample sizes varied from 77 to 349 participants. It was not possible to pool the data for meta-analysis.
Bromhexine (not available in the UK) compared with placebo
One RCT was identified (88 participants) that compared oral bromhexine 30 mg three times a day with placebo.
There was no difference between bromhexine and placebo for FEV1 (forced expiratory volume in the first second).
Some outcomes were improved by bromhexine compared with placebo: difficulty in expectoration (weighted mean difference on day 10; –0.45, 95% CI –0.89 to –0.03), percentage change in sputum production (weighted mean difference on day 16; –21.5, 95% CI –38.9 to –4.1), cough score (weighted mean difference on day 13; –0.48, 95% CI –0.89 to –0.06).
Harms were not reported in this study.
Recombinant human DNase (rhDNase; dornase alfa) compared with placebo
Two RCTs were identified that compared nebulized rhDNase with placebo.
One small study (77 participants) found no difference in FEV1 or FVC (forced vital capacity) on day 15 for rhDNase compared with placebo. Weighted mean differences could not be estimated in this review.
A larger study (349 participants) found that FEV1 was worse with rhDNase compared with placebo (mean percentage decline –1.7% with placebo and –3.6% with rhDNase). Standard deviations were not reported.
Adverse effects, including influenza-like symptoms, were more common with rhDNase.
Authors conclusions
There is not enough evidence to evaluate the routine use of mucolytics for bronchiectasis.
One Cochrane systematic review of inhaled hyperosmolar agents for bronchiectasis (search date: to October 2007) identified two small RCTs using inhaled mannitol that fulfilled the inclusion criteria [Wills and Greenstone, 2006]. Studies evaluating people with cystic fibrosis were excluded.
Quality of the included studies
Both were randomized crossover studies. One was a single-dose study compared with usual care, the other was double-blind and placebo-controlled but was only published as an abstract. Sample sizes were very small, from 11 to 17 participants.
Inhaled mannitol (not available in the UK) compared with placebo
A single-dose study found that tracheobronchial clearance (measured by percentage cleared radioactivity) was greater with inhaled mannitol than after usual care (coughing and inspiratory manoeuvres).
A double-blind placebo-controlled study comparing inhaled mannitol or placebo twice a day for 2 weeks (17 participants) found no difference in FEV1 between treatments. However, quality of life scores were improved with mannitol.
Antibiotics
Evidence on antibiotics for bronchiectasis
CKS found insufficient data to guide the choice of empirical antibiotic or the duration of treatment for an acute exacerbation of bronchiectasis. Limited data from studies of long-term antibiotics suggest only small clinical benefits, and no benefit in terms of exacerbation rates or lung function.
Short-term use of antibiotics during exacerbations
CKS found no randomized controlled trials (RCTs) on antibiotics for acute exacerbations of bronchiectasis.
Long-term use of antibiotics
One Cochrane systematic review of prolonged oral antibiotics for purulent bronchiectasis in children and adults (search date: to January 2008) identified nine small RCTs that fulfilled the inclusion criteria (378 participants) [Evans et al, 2007]. All studies were conducted in adults with stable bronchiectasis that had been diagnosed by bronchography or high resolution computed tomography (CT) of the chest. Studies evaluating people with cystic fibrosis were excluded.
Quality of the included studies
Seven studies were randomized, double-blind, and placebo-controlled. Two were crossover studies. Sample size varied from 12 to 122 participants.
There was significant heterogeneity between studies. Only limited meta-analysis could be undertaken because of differences in outcome reporting between studies.
Study regimens included: twice daily nebulized tobramycin; twice daily oral amoxicillin, erythromycin, or roxithromycin; and twice weekly azithromycin, oxytetracycline, or penicillin. Study durations varied between 4 weeks and 1 year.
Efficacy
Pooled data from two RCTs (110 participants) found a small benefit for antibiotics in terms of clinical response rate compared with placebo (Peto odds ratio 3.37, 95% CI 1.60 to 7.09).
Pooled data from three RCTs (120 participants) found no significant difference between long-term antibiotics and placebo for exacerbation rate (Peto odds ratio 0.96, 95% CI 0.27 to 3.46).
Pooled data from two RCTs (40 participants) found no significant difference between long-term antibiotics and placebo for forced expiratory volume in 1 second (mean difference –1.05%, 95% CI –6.83 to +4.93).
Harms
There was no difference in the rates of rash and diarrhoea between antibiotics and placebo in two studies.
Two studies of nebulized tobramycin reported more dyspnoea, wheezing, and chest pain with tobramycin than with placebo.
Authors' conclusions
The available evidence shows a small benefit for the use of long-term antibiotics in bronchiectasis.
Physiotherapy
Evidence on physiotherapy for bronchiectasis
It is not possible, from the limited available evidence, to assess the effectiveness of physiotherapy for people with bronchiectasis.
One Cochrane systematic review of bronchopulmonary hygiene physical therapy methods (search date: to January 2007) identified seven small trials with a total of 126 participants. All but one were of crossover design. Meta-analysis was not possible as the trials used different groups and outcomes.
Due to small sample sizes and the overall poor quality of the trials, there is insufficient evidence to support or refute the use of bronchopulmonary hygiene physical therapy in bronchiectasis [Jones and Rowe, 1998].
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of bronchiectasis, with additional searches for evidence in the following areas:
Oral antibiotics for acute exacerbations
Search dates
Date unrestricted – January 2010
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
bronchiectasis/, bronchiectasis.tw.
oral antibiotics.tw., antibiotics.tw.
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSh subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Sources of medicines information
The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (BNF)
electronic Medicines Compendium (eMC)
European Medicines Agency (EMEA)
References
ABPI Medicines Compendium (2007) Summary of product characteristics Ventolin evohaler. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]
ABPI Medicines Compendium (2008) Summary of product characteristics for Vibramycin 50 capsules. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk
ABPI Medicines Compendium (2010) Summary of product characteristics for Amoxil capsules 250mg. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]
Barker, A.F. (2002) Bronchiectasis. New England Journal of Medicine 346(18), 1383-1393.
Baxter, K. (Ed.) (2008) Stockley's drug interactions: a source book of interactions, their mechanisms, clinical importance and management. 8th edn. London: Pharmaceutical Press.
BNF 59 (2010) British National Formulary. 59th edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.
Bott, J., Blumenthal, S., Buxton, M. et al. (2009) Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax 64(Suppl 1), i1-i51.
Bradley, J.M., Moran, F. and Greenstone, M. (2002) Physical training for bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
British Thoracic Society (2010) Guideline for non-CF bronchiectasis. ..British Thoracic Society.www.brit-thoracic.org.uk [Free Full-text]
Bryskier, A. and Butzler, J.P. (2003)
Chang, C.C., Morris, P.S. and Chang, A.B. (2007) Influenza vaccine for children and adults with bronchiectasis (Cochrane Review). .Issue 3.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Chang, C.C., Singleton, R.J., Morris, P.S. and Chang, A.B. (2009) Pneumococcal vaccines for children and adults with bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Chung, K.F. and Pavord, I.D. (2008) Prevalence, pathogenesis, and causes of chronic cough. Lancet 371(9621), 1364-1374. [Abstract]
Corless, J.A. and Warburton, C.J. (2000) Leukotriene receptor antagonists for non-cystic fibrosis bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Crockett, A., Cranston, J.M., Alpers, J.H. and Latiner, K.M. (2001) Mucolytics for bronchiectasis (Cochrane Review). .Issue 1.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
CSM (1990) Beta-agonists, xanthines and hypokalaemia. Current Problems in Pharmacovigilance 28(May), 3. [Free Full-text]
CSM (1996) Drug-induced prolongation of the QT interval. Current Problems in Pharmacovigilance 22(March), 2. [Free Full-text]
CSM (2004) Statins and cytochrome P450 interactions. Current Problems in Pharmacovigilance 30(Oct), 1-2. [Free Full-text]
DTB (1991) Clarithro- and azithromycin: better erythromycins? Drug & Therapeutics Bulletin 29(26), 101-102.
DTB (2003) Management of bronchiectasis. Drugs and Therapeutics Bulletin 41(12), 91-95. [Abstract]
Ellis, D.A., Thornley, P.E., Wightman, A.J. et al. (1981) Present outlook in bronchiectasis: clinical and social study and review of factors influencing prognosis. Thorax 36(9), 659-664. [Abstract] [Free Full-text]
Evans, D.J., Bara, A. and Greenstone, M. (2007) Prolonged antibiotics for purulent bronchiectasis in children and adults (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Franco, F., Sheikh, A. and Greenstone, M. (2003) Short acting beta2-agonists for bronchiectasis (Cochrane Review). .Issue 1.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
FSRH (2009) UK medical eligibility criteria for contraceptive use. ..Faculty of Sexual and Reproductive Healthcare.www.fsrh.org [Free Full-text]
FSRH (2011) Drug interactions with hormonal contraception. ..Faculty of Sexual and Reproductive Healthcare.www.fsrh.org [Free Full-text]
Grenier, P., Maurice, F., Musset, D. et al. (1986) Bronchiectasis: assessment by thin-section CT. Radiology 161(1), 95-99. [Abstract]
HPA (2010) Personal communication. Health Protection Agency: London.
Jones, A.P. and Rowe, B.H. (1998) Bronchopulmonary hygiene physical therapy for chronic obstructive pulmonary disease and bronchiectasis (Cochrane Review) [Withdrawn]. .Issue 4.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Kapur, N., Bell, S., Kolbe, J. and Chang, A.B. (2009) Inhaled steroids for bronchiectasis (Cochrane Review). .Issue 1.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
King, P.T., Holdsworth, S.R., Freezer, N.J. et al. (2006) Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respiratory Medicine 100(12), 2183-2189. [Abstract]
Lane, D.J. (2003)
Lasserson, T.J., Holt, K., Evans, D.J. et al. (2001a) Anticholinergic therapy for bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Lasserson, T.J., Holt, K., Milan, S.J. and Greenstone, M. (2001b) Oral steroids for bronchiectasis (stable and acute exacerbations) (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Loebinger, M.R., Wells, A.U., Hansell, D.M. et al. (2009) Mortality in bronchiectasis: A long-term study assessing the factors influencing survival. European Respiratory Journal 34(4), 843-849. [Abstract] [Free Full-text]
McLean, A. (2008) Bronchiectasis: A new look at an old adversary. Australian Prescriber 31(3), 77-79. [Free Full-text]
MHRA (2007) Short-acting beta agonists: myocardial ischaemia. Drug Safety Update 1(5), 10. [Free Full-text]
MHRA (2008) Statins: interactions, and updated advice for atorvastatin. Drug Safety Update 1(6), 2-4. [Free Full-text]
Murray, M.P. and Hill, A.T. (2009) Non-cystic fibrosis bronchiectasis. Clinical Medicine 9(2), 164-169.
NICE (2013) Key therapeutic topics - medicines management options for local implementation. ..National Institute for Health and Clinical Excellence.www.nice.org.uk [Free Full-text]
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]
NPIS (2009) Clarithromycin. TOXBASE..National Poisons Information Service.www.toxbase.org
NPIS (2010a) Erythromycin. TOXBASE..National Poisons Information Service.www.toxbase.org
NPIS (2010b) Ciprofloxacin. TOXBASE..National Poisons Information Service.www.toxbase.org
NPIS (2010c) Doxycycline. TOXBASE..National Poisons Information Service.www.toxbase.org
NTIS (2008a) Use of erythromycin in pregnancy. TOXBASE..National Poisons Information Service.www.toxbase.org
NTIS (2008b) The treatment of infections in pregnancy. TOXBASE..National Poisons Information Service.www.toxbase.org
NTIS (2008c) Use of clarithromycin in pregnancy. TOXBASE..National Poisons Information Service.www.toxbase.org
O'Brien, C., Guest, P.J., Hill, S.L. and Stockley, R.A. (2000) Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care. Thorax 55(8), 635-642. [Abstract] [Free Full-text]
O'Donnell, A.E. (2008) Bronchiectasis. Chest 134(4), 815-823. [Abstract] [Free Full-text]
Pasteur, M.C., Helliwell, S.M., Houghton, S.J. et al. (2000) An investigation into causative factors in patients with bronchiectasis. American Journal of Respiratory and Critical Care Medicine 162(4 Pt 1), 1277-1284. [Abstract] [Free Full-text]
Prescription Pricing Division, Business Services Authority (Ed.) (2010) NHS drug tariff. April 2010 edn. London: The Stationery Office.
Rosen, M.J. (2006) Chronic cough due to bronchiectasis: ACCP evidence-based clinical practice guidelines. Chest 129(Suppl 1), 122S-131S. [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.
Sheikh, A., Nolan, D. and Greenstone, M. (2001) Long-acting beta2-agonists for bronchiectasis (Cochrane Review). .Issue 4.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
Shoemark, A., Ozerovitch, L. and Wilson, R. (2007) Aetiology in adult patients with bronchiectasis. Respiratory Medicine 101(6), 1163-1170. [Abstract]
SIGN and BTS (2008) 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]
Steele, K. and Greenstone, M. (2000) Oral methylxanthines for bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]
ten Hacken, N.H.T., Wijkstra, P.J. and Kerstjens, H.A.M. (2007) Treatment of bronchiectasis in adults. British Medical Journal 335(7629), 1089-1093.
Trent Drug Information Service (2001) Drugs in breast milk: quick reference guide. UKMiCentral...www.ukmicentral.nhs.uk
Wills, P.J. and Greenstone, M. (2006) Inhaled hyperosmolar agents for bronchiectasis (Cochrane Review). .Issue 2.John Wiley & Sons, Ltd.www.thecochranelibrary.com [Free Full-text]