Anticholinergic therapy for bronchiectasis

Abstract

Background

Anticholinergic agents block bronchoconstriction mediated by the vagus nerve and may also dry up bronchial secretions. They are effective in obstructive airways disease and may be beneficial in bronchiectasis

Objectives

To determine the effect of anticholinergic therapy in acute exacerbations and stable bronchiectasis.

Search methods

The Cochrane Airways Group Specialised Register was searched and bibliographies of retrieved papers were checked. Searches are current as of May 2011.

Selection criteria

Only randomised controlled trials were considered.

Data collection and analysis

Two reviewers assessed the retrieved studies working independently.

Main results

Twelve studies were identified, of which six were obtained for further scrutiny. One was translated from Italian. None met the inclusion criteria. An update search conducted in May 2011 did not yield any new studies.

Authors' conclusions

No formal recommendations can be made about the use of anticholinergic therapy in acute or stable bronchiectasis based on the literature currently available.

Plain language summary

The effects of anticholinergic drugs in the treatment of bronchiectasis

Bronchiectasis is a chronic respiratory disease. People with the condition experience difficulty in clearing mucus from their lungs, leaving them prone to infections. Atrovent and other anticholinergic agents are bronchodilators which could help with opening up the airways in people with bronchiectasis. We looked for randomised studies addressing this question but we could not identify any evidence for or against the use of anticholinergic drugs in the treatment of bronchiectasis.

Background

Bronchiectasis is a chronic respiratory condition that usually presents with chronic purulent sputum production or recurrent respiratory infections. Although most cases are idiopathic, recognised causes include congenital abnormalities, immunodeficiency, chronic inflammatory disorders and the sequelae of infection. Patients present at any age and eventually most will have evidence of asthma, fixed airflow obstruction and/or bronchial hyper‐reactivity. Lung damage is sometimes progressive and respiratory failure may develop. Management is aimed at symptom control and prevention of respiratory decline. Physical therapy (e.g. the active cycle of breathing technique with postural drainage) and antibiotics for control of infections are first line treatments. Cochrane systematic reviews have been conducted examining the role of such interventions as physical therapy (Jones 1998) and hyperosmolar agents (Wills 2001) for bronchiectasis.

Bronchiectasis is usually associated with an obstructive ventilatory defect (Cherniack 1997) and during exacerbations there is usually deterioration in the degree of airflow obstruction. A substantial proportion of patients with bronchiectasis also have asthma (Murphy 1984) but in others the airflow obstruction is only poorly reversible. Although inhaled beta2 agonists probably remain first line therapy for bronchiectasis related airflow obstruction some patients are treated with anticholinergic agents in the belief that they will have additional bronchodilator activity analogous to the use of these agents in smoking‐related COPD. The older anticholinergic agents tended to dry up bronchial secretions and slow mucociliary transport both of which might have a detrimental effect in patients with bronchiectasis.

Objectives

The objectives of this systematic review were to determine the efficacy of anticholinergic therapy:

1. To assess bronchodilator responsiveness in patients with bronchiectasis

2. During acute exacerbations of bronchiectasis

3. In stable bronchiectasis

Methods

Criteria for considering studies for this review

Types of studies

Only randomised controlled trials were considered for this review. All double blind studies were considered. Single blind and open studies were considered for inclusion.

Types of participants

All adults and children with bronchiectasis to be included, except those with cystic fibrosis

Types of interventions

Inhaled anticholinergic therapy administered either in exacerbation, in chronic stable disease or as a single physiological measurement of reversibility

Types of outcome measures

The most appropriate single or multiple outcome measure in bronchiectasis has not been defined. For the purposes of this review we have taken the decision to define our primary and secondary outcomes as:

Primary outcomes

Exacerbations: number and duration

Secondary outcomes

1. Symptoms: daily sputum volume, cough, dyspnoea, acute exacerbations

2. Health status (Quality of Life)

3. Change in lung function: e.g. forced expiratory volume in one second (FEV1)

4. Use of antibiotics

5. Decline in lung function

6. Morbidity: days off work, number and duration of hospital admissions

7. Mortality

8. Markers of systemic inflammation

Search methods for identification of studies

Electronic searches

Trials were identified using the Cochrane Airways Group Specialised Register of trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL, and handsearching of respiratory journals and meeting abstracts. All records in the Specialised Register coded as 'bronchiectasis' were searched using the following terms:

ipratropium* OR atrovent OR anticholinerg* or anti‐cholinerg* OR oxytropium OR tiotropium OR atropine

Searching other resources

The bibliographies of retrieved studies were searched for additional publications that might contain RCTs. Authors of RCTs were contacted for information on other published and unpublished studies.

Data collection and analysis

Selection of studies

The titles, abstracts and citations were reviewed to determine potential relevance for the full review

Assessment of risk of bias in included studies

We plan to assess the risk of bias in each study according to the following domains:

1. Randomisation and allocation concealment

2. Blinding (participants, personnel and outcome assessors)

3. The handling of withdrawals

4. Selective outcome reporting

5. Other biases (such as carryover or adjustment within patient observation in crossover studies)

Data synthesis

All included trials were to be analysed using Cochrane Review Manager software. Results were to be presented with 95% confidence intervals. Tests for heterogeneity would have been performed on the data.

Results

Description of studies

Despite extensive efforts to identify relevant studies, no randomised controlled trials have been found through electronic searches. Initial searches identified a total of 12 references. Six references were obtained for further scrutiny, and one Italian paper was translated and excluded (Sturani 1982). None of the papers met the inclusion criteria for the review. Subsequent update searches up to May 2011 did not yield any new studies for consideration.

Risk of bias in included studies

No studies could be assessed.

Effects of interventions

No data could be analysed.

Discussion

One small study (Abu Hassan 1999) documents a significant bronchodilator response in a subset of patients with bronchiectasis. Twenty‐four patients with confirmed bronchiectasis (diagnosed radiologically) underwent outpatient reversibility testing (peak expiratory flow rates and spirometry) to low and high doses of inhaled ipratropium bromide and fenoterol. The patients received 40 mcg and subsequently 500 mcg of ipratropium bromide following baseline measurements of lung function. Patients acted as their own controls but the order in which control, post beta‐agonist and anticholinergic measurements were made was not randomised and the measurements were made at only two time points. The study authors reported that 11 out of 28 patients responded (defined as > 15% improvement in FEV1) with 5 patients responding to both drugs, three to ipratropium alone and three to fenoterol alone. The level of response was approximately similar in the two treatment arms. In the absence of follow up data from longer‐term treatment no information is available on symptom control, exacerbation rate or health status. Although patients with a definite history of asthma were excluded, some individuals may have had mild unrecognised asthma and showed sufficiently large improvements in peak flow or FEV1 to meet the usual accepted reversibility criteria.

Asthma and bronchiectasis may co‐exist by chance but in some patients the underlying inflammatory process may have contributed to the development of both conditions. Until further evidence is available it would be reasonable to manage the airflow obstruction in the usual way including reversibility testing to low and high doses of bronchodilator drugs and a trial of oral corticosteroids. Whether there is any benefit in combining different classes of bronchodilator has not been examined but the evidence in COPD suggests it can be a useful approach. There are no data to determine whether anticholinergic agents have any long term benefit on the lung function abnormalities but this seems improbable given their lack of effect in smoking related COPD (Anthonisen 1994). In the absence of even short term data on the effects of anticholinergic agents on such basic measures as exercise tolerance or health status, it is unlikely that information on longer term outcomes such as exacerbation rate or decline in lung function will be available in the foreseeable future. Given the dearth of randomised controlled trials it is concluded that there is no unbiased evidence on the effect of anticholinergics in acute or stable bronchiectasis.

Authors' conclusions

Implications for practice.

No relevant trials have been published so this review concludes that there is no evidence to indicate that anticholinergic therapy is either beneficial or otherwise in the treatment of acute or stable bronchiectasis.

Implications for research.

Randomised clinical trials of reasonable duration examining the role of anticholinergic therapy in bronchiectasis are required.

What's new

Date	Event	Description
9 May 2011	New search has been performed	Literature searches were re‐run. No new studies were found.

History

Protocol first published: Issue 2, 1999
 Review first published: Issue 2, 2001

Date	Event	Description
7 April 2008	Amended	Converted to new review format.
1 January 2001	New citation required and conclusions have changed	Substantive amendment

Characteristics of studies

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abu Hassan 1999	Observational study
Sturani 1982	Sequential study

Contributions of authors

TJL: Assessed search results, data extraction, write‐up and interpretation 
 KH: Protocol initiation, assessed search results 
 DE: Write‐up and interpretation 
 MG: Editorial support and guidance throughout

Sources of support

Internal sources

• No sources of support supplied

External sources

• Garfield Weston Foundation, UK.

Declarations of interest

None known.

New search for studies and content updated (no change to conclusions)