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Antiinflammatory Effects of Long-Acting β2-Agonists in Patients With Asthma

A Systematic Review and Metaanalysis
  • Author Footnotes
    * Both authors contributed equally to the article.
    Anees Sindi
    Footnotes
    * Both authors contributed equally to the article.
    Affiliations
    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada
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  • Author Footnotes
    * Both authors contributed equally to the article.
    David C. Todd
    Footnotes
    * Both authors contributed equally to the article.
    Affiliations
    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada
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  • Author Footnotes
    2 Dr. Nair is supported by a Canada Research Chair in Airway Inflammometry.
    Parameswaran Nair
    Correspondence
    Correspondence to: Parameswaran Nair, MD, PhD, FCCP, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Ave East, Hamilton, ON, Canada L8N 4A6
    Footnotes
    2 Dr. Nair is supported by a Canada Research Chair in Airway Inflammometry.
    Affiliations
    Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, Hamilton, ON, Canada
    Search for articles by this author
  • Author Footnotes
    * Both authors contributed equally to the article.
    2 Dr. Nair is supported by a Canada Research Chair in Airway Inflammometry.

      Background

      Long-acting β2-agonists are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect.

      Methods

      A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity.

      Results

      Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4.

      Conclusion

      LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.

      Abbreviations:

      CI (confidence interval), ECP (eosinophilic cationic protein), ENO (exhaled nitric oxide), ICS (inhaled corticosteroid), IL (interleukin), LABA (long-acting β2-agonist), RCT (randomized controlled trial), SMD (standardized mean difference)
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