A systematic review of adverse drug events associated with administration of common asthma medications in children

PLoS One. 2017 Aug 9;12(8):e0182738. doi: 10.1371/journal.pone.0182738. eCollection 2017.

Abstract

Objective: To systematically review the literature and determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications.

Methods: Following PRISMA guidelines, we systematically searched six bibliographic databases between January 1991 and January 2017. Study eligibility, data extraction and quality assessment were independently completed and verified by two reviewers. We included randomized control trials (RCT), case-control, cohort, or quasi-experimental studies where the primary objective was identifying ADE in children 1 month- 18 years old exposed to commercial asthma medications. The primary outcome was ADE frequency.

Findings: Our search identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS) (n = 24), short-acting beta-agonists (n = 10), long-acting beta-agonists (LABA) (n = 3), ICS + LABA (n = 3), Leukotriene Receptor Antagonists (n = 3) and others (n = 3). 29 studies occurred in North America, and 29 were industry funded. We report a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data focuses on ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. We observed serious ADE, although they were rare, with frequency ranging between 0.9-6% per drug. There were no confirmed deaths, except for 13 potential deaths in a LABA study including combined adult and pediatric participants. We identified substantial methodological concerns, particularly with identifying ADE and determining severity. No studies utilized available standardized causality, severity or preventability assessments.

Conclusion: The majority of studies focus on ICS, with adrenal and growth suppression described. Serious ADE are relatively uncommon, with no confirmed pediatric deaths. We identify substantial methodological concerns, highlighting need for standardization with future research examining pediatric asthma medication safety.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-2 Receptor Agonists / adverse effects*
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Anti-Asthmatic Agents / adverse effects*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy*
  • Child
  • Child, Preschool
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Infant
  • Leukotriene Antagonists / adverse effects*
  • Leukotriene Antagonists / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Leukotriene Antagonists

Grants and funding

Dr. David W Johnson and this study are supported by a grant from the University of Calgary Emerging Team Fund. Dr. Lisa Hartling is supported by a New Investigator Salary Award from the Canadian Institutes of Health Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.