Asthma: beta-agonists probably increased the risk of a fatal attack.

Clinical bottom line (level 2a)

  1. Use of beta-agonists was associated with a small increase in the risk of having a fatal asthma attack (NNH = 360 at years) .
  2. This may only be for beta-agonists delivered by nebuliser (NNH = 70 at years) .
Mullen et al: Journal of the American Medical Association 1993; 270 (15): 1842-1845
Expires November 2002

The study

Systematic review of case-control studies of
  • Patients: asthma
  • Intervention: beta-agonists
  • Outcome: fatal asthma attack


    • Articles found in all using MEDLINE and Science Citation Index, 1966 to 1992 (search terms: beta-agonist and asthma ) and bibliographies were also searched and leading journals were hand searched

    Selection criteria: as above
    Appraisal criteria: selected two independent, blinded reviewers using set criteria (detailed in text)
    Articles excluded if:

    six studies found containing 364 cases and 1388 controls
    significant heterogeneity was noted between the studies.

    The evidence

    Patient expected event rate for death from asthma: 1.0%
    risk factor for
    death from asthma     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)    		 p-value
    use of beta-agonists 1.28
    ( to )     		360
    ( to )     		0.000032
    beta-agonist via nebuliser 2.47
    ( to )     		70
    ( to )     		0.00000038
    via metered-dose inhaler 1.28
    ( to )
    ( to )     		0.11
    orally 1.22
    ( to )
    ( to )     		0.1

    • Confidence intervals not given.

    Comments

    1. The paper does not comment whether each article was adjusted for confounding factors (such as severity of asthma). Typically patients only received nebulised beta-agonists if they have an asthma attack severe enough to attend hospital, suggesting such patients have more severe asthma anyway and consequently are at increased risk of dying.
    2. An RCT in mild asthma (Drazen 96) shows no deleterious nor beneficial effects of beta-agonists for mild asthma

    Citation

    1. Mullen M, Mullen B, Carey M: The association between beta-agonist use and death from asthma: a meta-analytic integration of case-control studies. Journal of the American Medical Association 1993; 270 (15): 1842-1845
    Search Terms: acute asthma in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient asthma
    Intervention or Exposure beta-agonists
    Outcome fatal asthma attack