Bronchiectasis

Abstract

Introduction

Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.

Results

We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, bronchopulmonary hygiene physical therapy, exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, beta₂ agonists, steroids (inhaled, oral), and surgery.

Key Points

Bronchiectasis is characterised by irreversible widening of medium-sized airways, with inflammation, chronic bacterial infection, and destruction of bronchial walls.

• Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and production of copious sputum, which is often purulent. Bronchiectasis may cause signs of COPD. It can also be associated with cystic fibrosis and other congenital disorders, foreign-body inhalation, and other causes of lung damage.

Exercise or inspiratory muscle training may improve quality of life and exercise endurance in people with bronchiectasis but without cystic fibrosis.

We do not know whether bronchopulmonary hygiene physical therapy, mucolytics, inhaled hyperosmolar agents, inhaled corticosteroids, oral corticosteroids, leukotriene receptor antagonists,short-acting beta₂ agonists , long-acting beta₂ agonists, anticholinergic therapy, or surgery are beneficial, because few studies have been found.

• Inhaled corticosteroids may reduce sputum volume compared with placebo, but have not been shown to reduce exacerbations.

• Oral methyl-xanthines and surgery are often used in bronchiectasis, but we found no good-quality studies of either treatment.

• Surgery is often considered for people with extreme damage to one or two lobes of the lung who are at risk of severe infection or bleeding.

• Prolonged-use antibiotics improve clinical response rates (according to treating physicians at follow-up), but may not reduce exacerbation rates or lung function compared with placebo.

About this condition

Definition

Bronchiectasis is defined as irreversible widening of medium-sized airways (bronchi) in the lung. It is characterised by inflammation, destruction of bronchial walls, and chronic bacterial infection. The condition may be limited to a single lobe or lung segment, or it may affect one or both lungs more diffusely. Clinically, the condition manifests as chronic cough and chronic overproduction of sputum (up to about 500 mL/day), which is often purulent. People with severe bronchiectasis may have life-threatening haemoptysis, and may develop features of chronic obstructive airways disease, such as wheezing, chronic respiratory failure, pulmonary hypertension, and right-sided heart failure.

Incidence/ Prevalence

We found few reliable data. Incidence has declined over the past 50 years, and prevalence is low in higher-income countries. Prevalence is much higher in lower-income countries, and is a major cause of morbidity and mortality.

Aetiology/ Risk factors

Bronchiectasis is most commonly a long-term complication of previous lower respiratory infections, such as measles pneumonitis, pertussis, and tuberculosis. Foreign-body inhalation and allergic, autoimmune, and chemical lung damage also predispose to the condition. Underlying congenital disorders such as cystic fibrosis, cilial dysmotility syndromes, alpha₁ antitrypsin deficiency, and congenital immunodeficiencies may also predispose to bronchiectasis — and may be of greater aetiological importance in higher-income countries than respiratory infection. Cystic fibrosis is the most common congenital cause. This review does not deal with bronchiectasis in people with cystic fibrosis.

Prognosis

Bronchiectasis is a chronic condition, with frequent relapses of varying severity. Long-term prognosis is variable. Data on morbidity and mortality are sparse. Bronchiectasis frequently coexists with other respiratory disease, making it difficult to distinguish prognosis for bronchiectasis alone.

Aims of intervention

To alleviate symptoms; to reduce morbidity and mortality.

Outcomes

Mortality, infection and exacerbation rates, symptom severity (for example sputum volume, cough, expectoration rates, haemoptysis), functional improvement (for example lung function and exercise tolerance), hospital admission, days off work, quality of life, adverse effects.

Methods

Clinical Evidence search and appraisal July 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to July 2007, Embase 1980 to July 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies, and we included open studies. We also searched for cohort studies, case-control studies, and case series for the surgery question. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table.

GRADE evaluation of interventions for bronchiectasis

Important outcomes	Mortality, infection and exacerbation rates, symptom severity (for example sputum volume, cough, expectoration rates, haemoptysis), functional improvement (for example lung function and exercise tolerance), hospital admission, days off work, quality of Life, adverse effects
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatments in people with bronchiectasis but without cystic fibrosis?
2 (43)	Function improvement	Exercise v no intervention/sham intervention	4	−3	0	−1	0	Very low	Quality points deducted for sparse data, incomplete reporting of results and for not stating method of assessment for endurance. Directness point deducted for co-intervention in active control group
2 (43)	Quality of life	Exercise v no intervention/sham intervention	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for co-intervention in active control group
3 (120)	Exacerbation rates	Prolonged antibiotics v placebo	4	−2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
3 (184)	Symptom severity	Prolonged antibiotics v placebo	4	−2	0	−1	+1	Low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for subjective outcome. Effect size added for OR>2
3 (114)	Function improvement	Prolonged antibiotics v placebo	4	−2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (45)	Symptom severity	Bromhexine v placebo	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for uncertainty about clinical importance
1 (42)	Infection rates	Recombinant human deoxyribonuclease (rhDNase) v placebo	4	−3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting of results, and uncertainty about length of follow up
1 (349)	Exacerbation rates	Recombinant human deoxyribonuclease (rhDNase) v placebo	4	−1	0	0	0	Moderate	Quality points deducted for incomplete reporting of results
1 (42)	Functional improvement	Recombinant human deoxyribonuclease (rhDNase) v placebo	4	−3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting of results and uncertainty about length of follow up
1 (86)	Exacerbation rates	Inhaled corticosteroids v placebo	4	−2	0	0	0	Low	Quality point deducted for sparse data and incomplete reporting of results
4 (233)	Symptom severity	Inhaled corticosteroids v placebo	4	−1	−1	0	0	Low	Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results
3 (140)	Functional improvement	Inhaled corticosteroids v placebo	4	−2	0	0	0	Low	Quality point deducted for sparse data and incomplete reporting of results
1 (93)	Quality of life	Inhaled corticosteroids v placebo	4	−2	0	0	0	Low	Quality point deducted for sparse data and incomplete reporting of results

Type of evidence: 4 = RCT; Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio

Glossary

Chronic Respiratory Disease Questionnaire (CRQ)

A 20-item questionnaire dealing with dimensions of dyspnoea, fatigue, patients' sense of control over disease (mastery), and emotional dysfunction. A trained interviewer needs 20 minutes to complete it. Answers are scored on a seven-point scale, ranging from 1, which indicates maximum impairment, to 7, which indicates no impairment.

Inspiratory muscle training (IMT)

People are required to breathe through inspiratory devices of progressively decreasing diameter, with the goal of increasing the load on the respiratory muscles. Another technique involves the use of a threshold loading device that lets inspiration commence only after a certain threshold mouth pressure is reached. The threshold pressure can be set by means of a weighted plunger. In most programmes, subjects have to train for 30 minutes a day, 5 days a week.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

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