Ducharme F M, Zemek R, Gravel J, Chalut D, Poonai N, Laberge S, Quach C, Krajinovic M, Guimont C, Lemière C, Guertin M C
Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
BMJ Open. 2014 Apr 7;4(4):e004699. doi: 10.1136/bmjopen-2013-004699.
Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids.
The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05.
Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations.
Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists.
This study is registered at Clinicaltrials.gov (NCT02013076).
口服皮质类固醇是急诊科急性哮喘治疗的基石。最近的证据对这种治疗方法在病毒诱发喘息的学龄前儿童和吸烟成年人中的疗效提出了质疑。本研究的目的是：（1）记录急诊科中患有中度或重度哮喘的儿童对口服皮质类固醇的反应程度；（2）量化皮质类固醇反应的潜在决定因素；（3）探索与皮质类固醇反应性相关的基因多态性的作用。
本研究为前瞻性队列研究，纳入1008名年龄在1至17岁之间、符合哮喘严格定义且在经过验证的儿科呼吸评估量表上临床评分为≥4分的儿童。所有儿童将接受泼尼松/泼尼松龙标准化的严重程度特异性治疗及联合干预措施（沙丁胺醇加/不加异丙托溴铵）。将客观记录决定因素，即病毒病因、环境烟草烟雾和单核苷酸多态性。主要疗效终点是急诊科就诊后72小时内急诊科治疗失败。次要终点包括哮喘严重程度的其他指标以及首次就诊后7天内的恢复时间。该研究在α为0.05时，有80%的把握度检测出与每个决定因素相关的风险差异，相对于21%的基线风险，风险差异为7.5%。
已获得所有参与机构的伦理批准。某些亚组中对全身类固醇反应受损将挑战当前的实践标准，并要求立即寻找更好的方法。潜在的宿主 - 环境相互作用将拓宽我们对儿童皮质类固醇反应性的理解。记录皮质类固醇在不同决定因素中的相似有效性将为当前治疗建议提供所需的保证。
研究结果将在国际会议上公布，并发表针对急诊科医生、儿科医生、遗传学家和呼吸科医生的手稿。
本研究已在Clinicaltrials.gov（NCT02013076）注册。
