Anticholinergic drugs versus either placebo or other medications for children over two years of age with asthma

Anticholinergic drugs are widely used in the management of both acute and chronic asthma in children. Their effect is achieved through relief of narrowing of the airways that occurs in asthma. Current guidelines for the management of chronic asthma advise that anticholinergic drugs may be used if children are already on high dose inhaled steroids. This study undertook a comprehensive search of the literature unrestricted by country of publication or language. Unfortunately small numbers of relevant trials were found and these were of variable quality. This review found that although anticholinergic drugs are well tolerated, in children over two years of age, there is not enough data to be sure if they are better than placebo in terms of effects on lung function or symptoms.

Authors' conclusions: 

The present review summarises the best evidence available to date. Although there were some small beneficial findings in favour of anticholinergic therapy, there is insufficient data to support the use of anticholinergic drugs in the maintenance treatment of chronic asthma in children.

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Background: 

In the intrinsic system of controlling airway calibre, the cholinergic (muscarinic) sympathetic nervous system has an important role. Anticholinergic, anti muscarinic bronchodilators such as ipratropium bromide are frequently used in the management of childhood airway disease. In asthma, ipratropium is a less potent bronchodilator than beta-2 adrenergic agents but it is known to be a useful adjunct to other therapies, particularly in status asthmaticus. What remains unclear is the role of anticholinergic drugs in the maintenance treatment of chronic asthma.

Objectives: 

To determine the effectiveness of anticholinergic drugs in chronic asthma in children over the age of 2 years.

Search strategy: 

The Cochrane Airways Group Specialised Register and reference lists of articles were searched. The most recent search was carried out in Febuary 2010.

Selection criteria: 

Randomised controlled trials in which anticholinergic drugs were given for chronic asthma in children over 2 years of age were included. Studies including comparison of: anticholinergics with placebo, and anticholinergics with any other drug were included.

Data collection and analysis: 

Eligibility for inclusion and quality of trials were assessed independently by two reviewers.

Main results: 

Eight studies met the inclusion criteria. Three papers compared the effects of anticholinergic drugs with placebo, and a meta-analysis of these results demonstrated no statistically significant benefit of the use of anticholinergic drugs over placebo in any of the outcome measures used. The results of one of these trials could not be included in the meta-analysis but the authors did report significantly lower symptom scores with inhaled anticholinergics compared with placebo. However, there was no significant difference between ipratropium bromide and placebo in the percentage of symptom-free nights or days. Two trials studied the effects of anticholinergics on bronchial hyper responsiveness to histamine, by measuring the provocation dose of histamine needed to cause a fall of 20 % in FEV1 (PD 20). One study (comparing anticholinergics with placebo) reported a statistically significant increase in PD 20 but this was not found in another study (comparing anticholinergics with a beta-2 agonist). Both trials also examined the effect of anticholinergic drugs on diurnal variation in peak expiratory flow rate (PEFR) and reported no significant effect. Two studies compared the addition of an anticholinergic drug to a beta-2 agonist with the beta-2 agonist alone. Both trials failed to show any significant benefit from the long term use of combined anticholinergics with beta-2 agonists compared with beta-2 agonists alone. One trial compared the effects of oral and inhaled anticholinergic drugs with placebo. No statistically significant differences were found in any of the outcome measures except for a higher FEV1 / VC ratio and RV / TLC ratio with oral anticholinergic therapy when compared with placebo.