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BMJ Clin Evid. 2008; 2008: 1507.
Published online 2008 January 2.
PMCID: PMC2907995

Bronchiectasis

Nick HT ten Hacken, MD, PhD, Pulmonary physician,# Professor Huib AM Kerstjens, MD, PhD, Professor of Pulmonary Medicine,# and Professor Dirkje S Postma, MD, PhD, Professor of Pulmonary Medicine#

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

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.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Nick HT ten Hacken, Pulmonary Department, University Hospital Groningen, Groningen, The Netherlands.

Professor Huib AM Kerstjens, Pulmonary Department, University Hospital Groningen, Groningen, The Netherlands.

Professor Dirkje S Postma, Pulmonary Department, University Hospital Groningen, Groningen, The Netherlands.

References

1. Nicotra MB, Riveera M, Dale AM, et al. Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort. Chest 1995;108:955–961. [PubMed]
2. Mysliwiec V, Pina JS. Bronchiectasis: the "other" obstructive lung disease. Postgrad Med 1999;106:123–131. [PubMed]
3. Keistinen T, Saynajakangas O, Tuuponen T, et al. Bronchiectasis: an orphan disease with a poorly-understood prognosis. Eur Respir J 1997;10:2784–2787. [PubMed]
4. Bradley J, Moran F, Greenstone M. Physical training for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005; primary sources Cochrane Airways Group trials register, Cochrane Clinical Register of Controlled Trials, hand searches of references, and contact with experts. [PubMed]
5. Evans DJ, Bara AI, Greenstone M. Prolonged antibiotics for purulent bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007; primary sources Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials, hand searches of respiratory journals, meetings abstracts, and references. [PubMed]
6. Couch LA. Treatment With tobramycin solution for inhalation in bronchiectasis patients with Pseudomonas aeruginosa. Chest 2001;120:114S–117S. [PubMed]
7. Lasserson TJ, Holt K, Evans D, et al. Anticholinergic therapy for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials, reference lists, and contact with authors. [PubMed]
8. Jones AP, Rowe BH. Bronchopulmonary hygiene physical therapy for chronic obstructive pulmonary disease and bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley and Sons, Ltd. Search date: 2005; primary sources Cochrane Airways Group Specialised Register of trials, contact with authors, hand searches of reference lists, and reviews. [PubMed]
9. Wills P, Greenstone M. Inhaled hyperosmolar agents for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005; primary sources Cochrane Airways Group Specialised Register of trials, Central reference lists, and contact with experts in the field.
10. Corless JA, Warburton CJ. Leukotriene receptor antagonists for non-cystic fibrosis bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005; primary sources Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials, hand searches of respiratory journals, meetings abstracts, and references. [PubMed]
11. Sheikh A, Nolan D, Greenstone M. Long-acting beta-2-agonists for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Controlled Trials Register, Medline, Embase, and hand searches of references. [PubMed]
12. Steele K, Lasserson JA, Greenstone M. Oral methyl-xanthines for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials, hand searches of respiratory journals, meetings abstracts, and references. [PubMed]
13. Crockett AJ, Cranston JM, Latimer KM, et al. Mucolytics for bronchiectasis. In: The Cochrane Library: Issue 2, 2007.Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Airways Group trials register, contact with pharmaceutical manufacturers, contact with experts, and hand searches of references. [PubMed]
14. O'Donnell AE, Barker AF, Ilowite JS, et al. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. Chest 1998;113:1329-1334 [PubMed]
15. Franco F, Sheikh A, Greenstone M. Short acting beta-2 agonists for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Central Register of Controlled Trials, Medline, Embase, Cinahl, the Cochrane Airways Group Specialised Register of trials, and references. [PubMed]
16. Kolbe J, Wells A, Ram FSF. Inhaled steroids for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2001; primary sources Cochrane Airways Group trials register, contact with pharmaceutical manufacturers, contact with experts, and hand searches of references. [PubMed]
17. Tsang KW, Tan KC, Ho PL, et al. Inhaled fluticasone in bronchiectasis: a 12 month study. Thorax 2005;60:239–243. [PMC free article] [PubMed]
18. Martinez-Garcia MA, Perpina-Tordera M, Roman-Sanchez P, et al. Inhaled steroids improve quality of life in patients with steady-state bronchiectasis. Respiratory Medicine 2006;100:1623–1632. [PubMed]
19. Lasserson T, Holt K, Greenstone M. Oral steroids for bronchiectasis (stable and acute exacerbations). In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Controlled Trials Register, Medline, Embase, and hand searching of references. [PubMed]
20. Corless JA, Warburton CJ. Surgery versus non-surgical treatment for bronchiectasis. In: The Cochrane Library: Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006; primary sources Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials, hand searches of respiratory journals, meetings abstracts, and references [PubMed]
2008; 2008: 1507.
Published online 2008 January 2.

Exercise or physical training

Summary

FUNCTIONAL IMPROVEMENT Compared with no intervention/sham intervention: Inspiratory muscle training or inspiratory muscle training plus pulmonary rehabilitation may be more effective than no intervention or sham inspiratory muscle training plus pulmonary rehabilitation at improving exercise endurance at 8 weeks in people with non-cystic fibrosis bronchiectasis ( very low-quality evidence ). QUALITY OF LIFE Compared with no intervention/sham intervention: Inspiratory muscle training or inspiratory muscle training plus pulmonary rehabilitation may be more effective than no intervention or sham inspiratory muscle training plus pulmonary rehabilitation at improving quality of life (assessed by Chronic Respiratory Disease Questionnaire scale) at 8 weeks in people with non-cystic fibrosis bronchiectasis (very low-quality evidence). NOTE We found no clinically important results about the effects of other types of exercise or physical training, or about exercises compared with other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review on inspiratory muscle training (search date 2005, 2 RCTs published in abstract form only, 52 people with non-cystic fibrosis bronchiectasis). We found no subsequent RCTs. The first RCT identified by the review compared inspiratory muscle training (IMT) for 8 weeks versus no intervention. The second RCT identified by the review compared three treatments for 8 weeks: IMT plus pulmonary rehabilitation; sham IMT plus pulmonary rehabilitation (including education plus exercise); and no intervention. However, no data were available for the no intervention group from this second RCT, and so the review pooled data for IMT versus no intervention from the first RCT and IMT plus pulmonary rehabilitation versus sham IMT plus pulmonary rehabilitation from the second RCT. The review found that IMT or IMT plus pulmonary rehabilitation significantly improved exercise endurance and quality of life compared with no intervention (43 people: endurance [method of assessment not described]: WMD 264 metres, 95% CI 16.4 metres to 512 metres; quality of life [measured on Chronic Respiratory Disease Questionnaire scale]: WMD 12.4, 95% CI 2.38 to 22.48). We found no RCTs of other types of exercise or physical training in people with non-cystic fibrosis bronchiectasis, and no RCTs comparing exercise versus other treatments.

Harms

The two RCTs gave no information on adverse effects.

Comment

Clinical guide:

There is some evidence that IMT improves quality of life and exercise endurance in people with non-cystic fibrosis bronchiectasis. No beneficial effects have been demonstrated for pulmonary rehabilitation.

Substantive changes

Exercise or physical training One previously included systematic review updated;no new data added, categorisation unchanged (Likely to be beneficial).

2008; 2008: 1507.
Published online 2008 January 2.

Prolonged-use antibiotics

Summary

EXACERBATION RATES Compared with placebo: Prolonged-use antibiotics may be no more effective than placebo at decreasing exacerbation rates ( low-quality evidence ). SYMPTOM SEVERITY Compared with placebo: Prolonged-use antibiotics may be more effective than placebo at improving response rates (physician assessment of diary cards, or of overall medical condition) in people with non-cystic fibrosis bronchiectasis, but we don't know about general health (low-quality evidence). FUNCTIONAL IMPROVEMENT Compared with placebo: We don't know whether prolonged-use antibiotics are more effective than placebo at improving lung function. We don't know whether inhaled tobramycin is more effective than placebo at increasing lung function at 4 weeks in people with non-cystic fibrosis bronchiectasis (low-quality evidence).

Benefits

We found one systematic review and one additional RCT, which compared prolonged-use antibiotics versus placebo or as-required treatment. The systematic review (search date 2007, 9 RCTs, 378 people with non-cystic fibrosis bronchiectasis) compared prolonged-use antibiotics versus placebo or as-required treatment.Only limited meta-analysis was possible owing to the diversity of the trial end points, and the differing ways in which the data were presented. The review found that prolonged antibiotic treatment significantly improved response rate (physician assessment of diary cards, or of overall medical condition) compared with placebo (2 RCTs, 110 people; OR 3.37, 95% CI 1.60 to 7.09). No significant differences were found between prolonged antibiotic treatment and placebo for exacerbation rates (3 RCTs, 120 people; OR; 0.96, 95% CI 0.27 to 3.46) or lung function (2 RCTs, 40 people; WMD –1.05, 95% CI, –6.93 to +4.83).The additional RCT (74 people with bronchiectasis colonised with pseudomonas) compared 300 mg aerosolised tobramycin solution for inhalation administered twice daily for 4 weeks compared with placebo. The RCT rated the general health of the people included in the study by physician assessment as improved (62% with tobramycin v 38% with placebo), worse (22% with tobramycin v 13% with placebo), and unchanged (16% with tobramycin v 49% with placebo), no P values or absolute figures given; significance not reported. The RCT also found that people with bronchiectasis showed a small decline in pulmonary function after 4 weeks of treatment compared with placebo (decrease of 2.3% with tobramycin v increase of 1.5% with placebo; results presented graphically, no P value reported; significance not reported).

Harms

The systematic review reported no significant difference in withdrawals for prolonged-use antibiotics compared with placebo (5 RCTs, 258 people; OR 1.06, 95% CI 0.42 to 2.65), diarrhoea (2 RCTs, 148 people; OR 2.47, 95% CI 0.91 to 6.71), rash (2 RCTs, 57 people; OR 1.94, 95% CI 0.19 to 19.47), or death (2 RCTs, 127 people; OR 0.57, 95% CI 0.07 to 4.54). The additional RCT reported more treatment-emergent adverse events in the tobramycin group compared with the placebo group. The most common complaints were dyspnoea, wheezing, and chest pain.

Comment

None.

Substantive changes

Prolonged-use antibiotics One previously included systematic review updated;benefits and harms data enhanced, categorisation unchanged (Likely to be beneficial).

2008; 2008: 1507.
Published online 2008 January 2.

Anticholinergic therapy

Summary

We found no clinically important results from RCTs about anticholinergic therapy compared with no active treatment or other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2006), which identified no RCTs of anticholinergic therapy (ipratropium bromide, oxitropium, tiotropium, or atropine) in people with non-cystic fibrosis bronchiectasis. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Anticholinergic therapy One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Bronchopulmonary hygiene physical therapy (airway-clearance techniques)

Summary

We found no clinically important results from RCTs about the effects of bronchopulmonary hygiene physical therapy in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2005), which did not identify any RCTs that met inclusion criteria for this review. The review identified one crossover RCT solely in people with non-cystic fibrosis bronchiectasis. However, this RCT was not large enough to meet standard inclusion criteria for this review (at least 10 people per treatment group).

Harms

The review gave no information on adverse effects in people with bronchiectasis.

Comment

The authors of the review concluded that there is a need for adequately sized, high-quality RCTs with uniform populations, to examine the effects of bronchopulmonary hygiene physical therapy.

Clinical guide:

There is insufficient evidence to support or refute administration of bronchopulmonary hygiene physical therapy (airway-clearance techniques) in patients with stable bronchiectasis.

Substantive changes

No new evidence

2008; 2008: 1507.
Published online 2008 January 2.

Hyperosmolar agents (inhaled)

Summary

We found no clinically important results from RCTs about the effects of inhaled hyperosmolar agents in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2005), which identified no high-quality RCTs of inhaled hyperosmolar agents in people with non-cystic fibrosis bronchiectasis.We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

Clinical guide:

The objective of hyperosmolar inhalation treatment is to accelerate tracheobronchial mucociliary clearance, potentially by inducing a liquid flux into the airway surface. This approach differs conceptually from the use of mucolytics, which break down the mucus, making it less viscous and easier to cough up.

Substantive changes

No new evidence

2008; 2008: 1507.
Published online 2008 January 2.

Leukotriene receptor antagonists

Summary

We found no clinically important results from RCTs about leukotriene receptor antagonists compared with no active treatment or other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2005), which identified no RCTs in people with non-cystic fibrosis bronchiectasis. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Leukotriene receptor antagonists One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Long-acting beta2 agonists

Summary

We found no clinically important results from RCTs about long-acting beta 2 agonists compared with no active treatment or other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2006), which identified no RCTs in people with non-cystic fibrosis bronchiectasis. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Long-acting beta2 agonists One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Methyl-xanthines (oral)

Summary

We found no clinically important results from RCTs about oral methyl-xanthines compared with no active treatment or other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2006), which identified no RCTs in people with non-cystic fibrosis bronchiectasis. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

Clinical guide:

The authors of the systematic review conclude that they cannot support or refute the practice of using methyl-xanthines in bronchiectasis. Physicians may well continue to use this treatment on an empirical or trial basis, but will wish to be aware that the practice is not evidence based.

Substantive changes

Methyl-xanthines (oral) One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Mucolytics (bromhexine and deoxyribonuclease)

Summary

INFECTION RATES Recombinant human deoxyribonuclease (rhDNase) compared with placebo: We don't know whether recombinant human deoxyribonuclease is more effective than placebo at decreasing infection rates in people with non-cystic fibrosis bronchiectasis ( very low-quality evidence ). EXACERBATION RATES Recombinant human deoxyribonuclease (rhDNase) compared with placebo: Recombinant human deoxyribonucleas seems to be no more effective than placebo at decreasing rates of exacerbation in people with non-cystic fibrosis bronchiectasis ( moderate-quality evidence ). SYMPTOM SEVERITY Bromhexine compared with placebo: Bromhexine may be more effective than placebo at reducing sputum volume at 2 weeks. Bromhexine may be more effective than placebo at improving symptom scores (difficulty with expectoration, cough and quality of sputum) at 2 weeks, although the clinical importance of these score changes is uncertain (very low-quality evidence). FUNCTIONAL IMPROVEMENT Recombinant human deoxyribonuclease (rhDNase) compared with placebo: We don't know whether recombinant human deoxyribonucleas is more effective than placebo at improving lung function in people with non-cystic fibrosis bronchiectasis (very low-quality evidence). NOTE We found no clinically important results about mucolytics compared with other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review in people with non-cystic fibrosis bronchiectasis (search date 2006, 3 double-blind RCTs, total number of people not reported).

Bromhexine versus placebo:

The review identified one RCT (45 people with acute exacerbation of bronchiectasis [defined as morning cough and more than 20 mL sputum]) comparing bromhexine (30 mg 3 times/day) versus placebo. It found that bromhexine significantly reduced sputum volume after about 2 weeks compared with placebo (WMD –21.5%, 95% CI –38.9% to –4.1%). The review found that bromhexine significantly improved symptom scores compared with placebo for “difficulty with expectoration”, “cough”, and “quality of sputum” after about 2 weeks (difficulty in expectoration at day 10: WMD –0.45, 95% CI –0.89 to –0.03; cough score at day 13: WMD –0.48, 95% CI –0.89 to –0.06; quality of sputum at day 13: WMD –0.45, 95% CI –0.87 to –0.034),although the clinical importance of these score changes is uncertain.

Recombinant human deoxyribonuclease (rhDNase) versus placebo:

The review identified two RCTs comparing rhDNase aerosol versus placebo. The first RCT found no significant difference between rhDNase (2.5 mg in 2.5 mL, once or twice daily) and placebo in lung function or infection rates (time to outcome not reported; infection rates reported for once-daily dose: 4/21 [19%] with placebo v 0/21 [0%] with rhDNase; P greater than 0.1; no further numerical data reported). The second RCT also found no significant difference in exacerbation rates between rhDNase (twice daily for 24 weeks) and placebo (349 people:AR for exacerbation in 168 days: 0.66 with rhDNase v 0.56 with placebo; RR 1.17; 95% CI 0.85 to 1.65).

Mucolytics versus other treatments:

We found no RCTs.

Harms

Bromhexine versus placebo:

The RCT identified by the review gave no information on adverse effects.

Recombinant human deoxyribonuclease versus placebo:

In one RCT identified by the review, more people had influenza-type symptoms with rhDNase (5 mg/day) than with placebo (4 people with rhDNase v 0 with placebo, CI not reported). Other adverse effects were not specifically reported.

Mucolytics versus other treatments:

We found no RCTs.

Comment

Clinical guide:

There is little evidence to recommend mucolytics in stable bronchiectasis. During an exacerbation, some beneficial effects have been demonstrated after 2 weeks' treatment with bromhexine.

Substantive changes

Mucolytics (bromhexine or deoxyribonuclease) One previously included systematic review updated;benefits data enhanced, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Short-acting beta2 agonists

Summary

We found no clinically important results from RCTs about short-acting beta 2 agonists compared with no active treatment or other treatments in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2006), which identified no RCTs in people with non-cystic fibrosis bronchiectasis. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Short-acting beta2 agonists One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Corticosteroids (inhaled)

Summary

EXACERBATION RATES Compared with placebo: Inhaled corticosteroids may be no more effective at decreasing exacerbations in people with non-cystic fibrosis bronchiectasis ( low-quality evidence ). SYMPTOM SEVERITY Compared with placebo: Inhaled corticosteroids may be more effective than placebo at decreasing sputum volume at 6 and 12 months, but not in improving symptom scores or sputum volume at 4 to 6 weeks in people with non-cystic fibrosis bronchiectasis (low-quality evidence). FUNCTIONAL IMPROVEMENT Compared with placebo: Inhaled corticosteroids may be no more effective than placebo at improving lung function in people with non-cystic fibrosis bronchiectasis (low-quality evidence). QUALITY OF LIFE Compared with placebo: Inhaled corticosteroids may be more effective than placebo at improving quality of life (assessed by the St George respiratory questionnaire) in people with non-cystic fibrosis bronchiectasis (low-quality evidence).

Benefits

Corticosteroids (inhaled) versus placebo:

We found one systematic review (search date 2001, 2 double-blind RCTs, 54 people with bronchiectasis not due to congenital disease or focal airway obstruction) and two subsequent RCTs. RCTs included in the review compared inhaled corticosteroids (beclomethasone 1500 µg/day or fluticasone 1000 µg/day) versus placebo. The review found no significant difference between inhaled corticosteroids and placebo in symptom scores (75 mm visual analogue scale for corticosteroids v placebo: mean improvement in cough score +5 mm, 95% CI –28 mm to +38 mm; mean improvement in dyspnoea score +4 mm, 95% CI –33 mm to +41 mm), lung function indices (improvement in FEV1: +0.4 L/minute, 95% CI –2.2 L/minute to +1.0 L/minute; improvement in forced vital capacity: +0.6 L, 95% CI –0.1 L to +1.3 L), or sputum volume (reduction in sputum volume: +0.2 mL/day, 95% CI –0.4 mL/day to +0.7 mL/day) after 4–6 weeks. The review reported that the RCTs lacked power to detect clinically important effects. The first subsequent double-blind RCT found that fluticasone (500 µg twice/day) significantly increased the proportion of people with greater than 20% improvement in 24-hour sputum volume at 12 months compared with placebo (86 people; intention-to-treat analysis; AR for sputum volume improvement more than 20%: 65% with fluticasone v 42% with placebo; OR 2.5, 95% CI 1.1 to 6.0). The RCT measured sputum volume as the mean of three 24-hour collections after chest physiotherapy. It found no significant difference between fluticasone and placebo in the proportion of people with improvement in exacerbation frequency, or greater than 20% improvement in sputum purulence (scored on a scale of 0–8 by a technician), forced vital capacity, or FEV1 (improvement in exacerbations per year: 51% with fluticasone v 37% with placebo, P = 0.37; AR for greater than 20% improvement in sputum purulence score: 30% with fluticasone v 21% with placebo; AR for greater than 20% improvement in % of predicted FEV1: 4.7% with fluticasone v 7.0% with placebo; AR for greater than 20% improvement in % of predicted forced vital capacity: 9.3% with fluticasone v 9.3% with placebo, reported as not significant; P values and CI not reported). Subgroup analysis in the first subsequent RCT suggested that fluticasone may be more effective in people with bronchiectasis and Pseudomonas aeruginosa infection.The second subsequent RCT (93 people) compared the effects of inhaled fluticasone propionate (500 or 1000 µg/day) versus placebo.It did not report a between-group analysis for changes in lung function or for exacerbations. It found that fluticasone 1000 µg/day significantly improved dyspnoea, daily sputum production, and the need for short-acting beta2 agonists at 6 months compared with placebo (people improving over 1 point on transition dyspnoea index [TDI]: 19/29 [66%] with fluticasone v 10/28 [36%] with placebo, P = 0.02; difference in daily sputum production between fluticasone and placebo: –8.3 mL, P = 0.04; weekly need for short-acting beta2 agonists: 2.72 with fluticasone v 5.11 with placebo, P = 0.01). It found that fluticasone 1000 µg daily increased the proportion of people with a clinically significant improvement in health-related quality of life compared with 500 µg daily fluticasone and placebo (defined as increase in score of 4 or more measured by the St George Respiratory Questionnaire: 7.4% with placebo v 34.4% with 500 µg/day fluticasone v 51.7% with 1000 µg/day fluticasone; P = 0.009).

Corticosteroids (inhaled) versus other treatments:

We found no RCTs comparing inhaled corticosteroids versus other treatments.

Harms

Corticosteroids (inhaled) versus placebo:

The systematic review gave no information on adverse effects. The first subsequent RCT found no significant difference in withdrawal for any reason between fluticasone and placebo (8/43 [19%] with fluticasone v 5/43 [12%] with placebo; P = 0.37).The second subsequent RCT found adverse events to be significantly more frequent after 6 months' treatment with fluticasone 1000 µg daily compared with fluticasone 500 µg daily (19 with fluticasone 1000 µg/day v 7 with fluticasone 500 µg/day, P = 0.04; further details of adverse effects by group not reported), and did not report a statistical analysis of adverse effects between fluticasone and placebo.

Corticosteroids (inhaled) versus other treatments:

We found no RCTs.

Comment

Clinical guide:

There is no evidence of a clear positive clinical effect . In clinical practice, an individual therapeutic trial may be warranted in those patients with troublesome symptoms or severe functional impairment, especially if antibacterial requirements are high. This “expert opinion” is a partial restatement of that expressed in the Cochrane review, and the authors of this review concur with it.

Substantive changes

Corticosteroids (inhaled) One RCT added;benefits and harms data enhanced, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Corticosteroids (oral)

Summary

We found no clinically important results from RCTs about oral corticosteroids compared with no treatment, or other treatments, in people with non-cystic fibrosis bronchiectasis.

Benefits

We found one systematic review (search date 2006), which identified no RCTs in people with non-cystic fibrosis bronchiectasis.We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

None.

Substantive changes

Corticosteroids (oral) One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).

2008; 2008: 1507.
Published online 2008 January 2.

Surgery

Summary

We found no clinically important results from RCTs about surgical treatments compared with non-surgical treatments in people with bronchiectasis.

Benefits

We found one systematic review (search date 2006), which found no RCTs comparing surgical resection versus standard non-surgical treatments (see comments). The systematic review found only case series and case controlled studies of surgery for bronchiectasis. Although surgery is widely used, the authors concluded that it was not possible to provide an unbiased estimate of the effect of surgical treatment compared with conservative therapy. We found no subsequent RCTs.

Harms

We found no RCTs.

Comment

Clinical guide:

RCTs are very difficult to perform in this area for a number of reasons — including the small number of people with bronchiectasis eligible for surgery, the long follow-up time required to draw definitive conclusions, variations in surgical techniques currently in use, and ethical considerations. There is some general consensus about the indications for surgery — most physicians consider surgical resection in cases of extremely damaged lung segments or lobes that may be a focus for serious infection or bleeding. Bronchiectasis must be confined to one or two lobes for surgery to be considered.

Substantive changes

Surgery One previously included systematic review updated;no new data added, categorisation unchanged (Unknown effectiveness).


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