Marangu Diana, Kovacs Stephanie, Walson Judd, Bonhoeffer Jan, Ortiz Justin R, John-Stewart Grace, Horne David J
Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
Department of Epidemiology, University of Washington, Seattle, WA, United States.
Vaccine. 2015 Oct 5;33(41):5333-5341. doi: 10.1016/j.vaccine.2015.08.060. Epub 2015 Aug 28.
Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs).
To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement.
We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement.
Of 1205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity.
Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated.
喘息是疫苗和药物试验中表明可能发生严重不良事件的重要体征，在儿童中尤为如此。然而，目前在随机对照试验（RCT）中，对于喘息或相关呼吸功能损害尚无共识定义。
确定在纳入5岁以下儿童的疫苗和药物RCT中，作为不良事件的喘息的定义和严重程度分级量表，并根据敏感性、特异性和观察者间一致性确定其诊断性能。
我们对电子数据库和参考文献列表进行了系统综述，对试验设置、英语语言和出版日期≥1970年进行了限制。提取喘息定义和严重程度分级，并根据基于敏感性、特异性和观察者间一致性的诊断确定性评分进行排序。
在使用我们广泛的搜索词识别出的1205篇文章中，我们确定了在38个国家进行的58项符合条件的试验，主要是在高收入环境中。疫苗构成了干预措施的大多数（90%），尤其是流感疫苗（65%）。只有15项试验提供了喘息的明确定义。在描述严重程度的24项研究中，11项在明确的喘息定义背景下描述了喘息严重程度。其余13项研究在将喘息定义为呼吸道疾病的一部分或喘息等效物的情况下描述了喘息严重程度。喘息描述来自照顾者报告（14%）、卫生工作者的体格检查（45%）或两者结合（41%）。在58项研究中有21项，其中喘息定义包括照顾者报告和医护人员评估相结合。使用这两种方法似乎具有最高的综合敏感性和特异性。
缺乏用于儿科疫苗或药物试验的标准化喘息定义和严重程度分级量表。在评估新疫苗和药物时，需要标准化的喘息定义来评估可能的不良事件。
