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

PLOS ONE, Dec 2019

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.

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

August A systematic review of adverse drug events associated with administration of common asthma medications in children James S. Leung 0 1 David W. Johnson 0 Arissa J. Sperou 0 Jennifer Crotts 0 Erik Saude 0 Lisa Hartling 0 2 Antonia Stang 0 0 Editor: Imti Choonara, University of Nottingham , UNITED KINGDOM 1 Division of Pediatric Emergency Medicine, Department of Pediatrics, McMaster University , Hamilton, Ontario , Canada , 2 Departments of Pediatrics, Emergency Medicine, and Physiology and Pharmacology, University of Calgary, Alberta Children's Hospital Research Institute , Calgary, Alberta , Canada , 3 Cumming School of Medicine, University of Calgary , Calgary, Alberta , Canada , 4 Departments of Pediatrics, Emergency Medicine, Pediatric Emergency Research Institute , Calgary, Alberta , Canada , 5 Departments of Emergency Medicine and Pediatric Emergency Medicine, University of Calgary , Calgary, Alberta , Canada 2 Alberta Research Center for Health Evidence, Department of Pediatrics, University of Alberta , Edmonton, Alberta , Canada , 7 Departments of Pediatrics, Emergency Medicine, and Community Health Sciences, University of Calgary, Alberta Children's Hospital Research Institute , Calgary, Alberta , Canada Methods - 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 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. 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 Objective Methods Findings collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. 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. Introduction Wheeze is a common childhood problem, affecting one in three children before their third birthday, and almost 50% by 6 years of age.[ 1, 2 ] To treat this wheeze, asthma medications are frequently prescribed to children, regardless of a clear-cut diagnosis of asthma, which is particularly difficult in pre-school aged children and infants who present with bronchiolitis.[3] Considering their frequent labeled and off-labelled use, an understanding of adverse drug events associated with asthma medications is crucial to safe medical practice. Defined by the World Health Organization (WHO) as ªany untoward medical occurrence that may present itself during treatment with a medicine but which does not necessarily have a casual relationship with the treatmentº, Adverse Drug Events (ADE), are a measure of harm from medication administration.[ 4, 5 ] These ADE include harm from appropriately administered medications at appropriate doses (Adverse Drug Reactions, ADR), along with harm from inappropriately administered medications (Harmful Medical Error)[4]. The Global Initiative for Asthma (GINA) describes the following classes of medications to be used with asthmatic patients: short-acting beta agonists (SABA), inhaled corticosteroids (ICS), long-acting beta agonists (LABA), leukotriene receptor antagonists (LTRA), systemic corticosteroids (SCS) and IgE Immunomodulators (Anti-IgE).[ 6 ] Despite their common use, [ 7, 8 ] there is a paucity in understanding ADE associated with common asthma medications in children. For example, a broad systematic review focusing on ADR in children specifically excluded studies focusing on asthma.[9] We conducted a systematic review with the primary objective to determine the frequency of all ADE associated with commonly used asthma medications in children. Our secondary objectives were to describe the causality, severity and pr (...truncated)


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James S. Leung, David W. Johnson, Arissa J. Sperou, Jennifer Crotts, Erik Saude, Lisa Hartling, Antonia Stang. A systematic review of adverse drug events associated with administration of common asthma medications in children, PLOS ONE, 2017, Volume 12, Issue 8, DOI: 10.1371/journal.pone.0182738