Leung James S, Johnson David W, Sperou Arissa J, Crotts Jennifer, Saude Erik, Hartling Lisa, Stang Antonia
Division of Pediatric Emergency Medicine, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Departments of Pediatrics, Emergency Medicine, and Physiology and Pharmacology, University of Calgary, Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
PLoS One. 2017 Aug 9;12(8):e0182738. doi: 10.1371/journal.pone.0182738. eCollection 2017.
To systematically review the literature and determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications.
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.
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.
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.
系统回顾文献并确定与儿科哮喘药物相关的药物不良事件（ADE）的发生率。
遵循PRISMA指南，我们在1991年1月至2017年1月期间系统检索了六个文献数据库。研究的纳入标准、数据提取和质量评估由两位审阅者独立完成并核实。我们纳入了随机对照试验（RCT）、病例对照研究、队列研究或准实验研究，这些研究的主要目的是确定1个月至18岁接触商业哮喘药物的儿童中的ADE。主要结局是ADE的发生率。
我们的检索共识别出14540条引文。纳入了46项研究：24项RCT、15项队列研究、4项RCT汇总分析、1项病例对照研究、1项开放标签试验和1项准实验研究。研究涉及以下药物类别：吸入性糖皮质激素（ICS）（n = 24）、短效β受体激动剂（n = 10）、长效β受体激动剂（LABA）（n = 3）、ICS + LABA（n = 3）、白三烯受体拮抗剂（n = 3）及其他（n = 3）。29项研究在北美进行，29项由行业资助。我们报告了按药物类别组织的406条ADE描述及发生率的详细索引。大多数数据集中在ICS，有174例ADE影响13个器官系统，包括肾上腺抑制和生长抑制。我们观察到了严重的ADE，尽管很罕见，每种药物的发生率在0.9%至6%之间。除了一项包括成人和儿童参与者的LABA研究中有13例潜在死亡外，没有确诊死亡病例。我们发现了大量方法学问题，特别是在识别ADE和确定严重程度方面。没有研究采用现有的标准化因果关系、严重程度或可预防性评估。
大多数研究集中在ICS，描述了肾上腺抑制和生长抑制情况。严重的ADE相对不常见，没有确诊的儿科死亡病例。我们发现了大量方法学问题，突出了未来研究儿科哮喘药物安全性时进行标准化的必要性。
