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Review: anticholinergics in addition to β2 agonists improve outcome in children and adults with acute asthma
  1. Frank Thien, MD, FRACP
  1. Alfred Hospital and Monash University,
 Melbourne, Victoria, Australia

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 Q In children and adults with acute asthma exacerbations, do inhaled anticholinergic agents plus β2 agonists improve outcome more than β2 agonists alone?

    Clinical impact ratings GP/FP/Primary care ★★★★★★☆ Internal medicine ★★★★★★☆ Emergency medicine ★★★★★★☆ Allergy & immunology ★★★★★★☆ Respirology ★★★★★☆☆ Paediatrics ★★★★★★☆


    Embedded ImageData sources:

    Medline, EMBASE/Excerpta Medica, CINAHL, and the Cochrane Controlled Trials Register (to April 2005); hand searches of the reference lists of relevant articles and the top 20 respiratory journals; and the pharmaceutical company.

    Embedded ImageStudy selection and assessment:

    randomised controlled trials (RCTs), published as full articles in any language, that compared single or repeated doses of inhaled anticholinergic agents plus inhaled β2 agonists with inhaled β2 agonists alone for treatment of children (1.5–17 y of age) or adults (⩾18 y of age) with acute exacerbations of asthma presenting at the emergency department. RCTs involving atropine were excluded. 2 reviewers independently assessed the RCTs for inclusion and methodological quality (using the 5 point Jadad scale).

    Embedded ImageOutcomes:

    hospital admissions and change from baseline in spirometric test results at 1–2 hours after the last treatment.


    32 RCTs (1564 children; 2047 adults) met the selection criteria. The anticholinergic agent used was ipratropium bromide in 29 RCTs, oxitropium bromide in 2 RCTs, and glycopyrrolate in 1 RCT. The median Jadad score was 3 (range 1–5). Anticholinergics plus β2 agonists reduced the risk of hospital admission and improved spirometric test results more than β2 agonists alone in both children and adults (table). There was no evidence of an increase in side effects, such as tremors or heart rate changes, with anticholinergics.

    Anticholinergic agents plus β2 agonists (intervention) v β2 agonists alone (control) for acute asthma*


    In children and adults with acute asthma exacerbations presenting at the emergency department, inhaled anticholinergic agents plus β2 agonists reduce hospital admissions and improve measures of respiratory function more than β2 agonists alone.


    Exacerbations of asthma presenting as acute attacks are usually triggered by viral infections, with the main mechanism of airflow obstruction being airway smooth muscle spasm. Inhaled short acting β2 agonists (SABAs), acting through stimulation of the β2 adrenergic receptor, are the drugs of first choice to relieve bronchospasm for 2 reasons: (1) they are most rapid in onset of action (within minutes) and (2) they produce the greatest degree of bronchodilatation.

    Acting via a different mechanism, antagonism of the muscarinic cholinergic receptor, anticholinergic agents, such as ipratropium and oxitropium, can produce an additional 10–15% bronchodilatation. Although their onset of action is slower (30−60 mins), the duration of bronchodilator effect (4–6 h) is slightly more prolonged than that of the SABAs (3−4 h). Anticholinergics have a very low side effect profile, even with multiple doses.

    The meta-analysis by Rodrigo and Castro-Rodriguez confirms the benefit of adding an anticholinergic agent to inhaled SABAs in the management of moderate to severe acute asthma in children and adults. The trends towards greater benefit in more severe asthma and with multiple rather than single doses of anticholinergics are consistent with its pharmacological effect. Clinical judgement is required to determine the severity of asthma and number of doses administered. Local health economics will also influence the degree to which the cost of adding inhaled anticholinergics is offset by the benefit of reduction in cost of hospital admissions.

    A further aspect of this paper worth highlighting is that 7 of the 32 trials analysed used metered dose inhalers (MDIs) rather than nebulisers for administration of the inhaled medications. Another Cochrane review found that MDIs with a holding chamber are at least as efficacious as nebulisers for the administration of SABAs in treating acute asthma.1 More widespread acceptance of this administration method may move the cost benefit ratio further in favour of adding anticholinergics.


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    • For correspondence: Dr G J Rodrigo, Hospital Central de las FF.AA, Montevideo, Uruguay. gurodrig{at}

    • Source of funding: no external funding.