Juarez-Colunga Elizabeth, Rosenfeld Margaret, Zemanick Edith T, Wagner Brandie
Department of Biostatistics and Informatics, University of Colorado School of Public Health, USA; Adult and Child Consortium for Health Outcomes Research and Delivery Science, USA.
Department of Pediatrics, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE Seattle, WA 98105, USA.
J Cyst Fibros. 2020 Jan;19(1):114-118. doi: 10.1016/j.jcf.2018.12.005. Epub 2019 Jan 11.
Pulmonary exacerbations (PEx) are important contributors to morbidity and mortality in cystic fibrosis (CF). Understanding risk factors for PEx is critical to improve treatment; pulmonary exacerbations also serve as an important outcome in CF clinical trials. Current risk estimates generally only evaluate time to the first PEx. Methods accounting for multiple exacerbations during the observation period could provide more power to detect significant risk factors.
The Early Pseudomonas Infection Control (EPIC) Observational Study enrolled participants between 2004 and 2006 who were ≤ 12 years of age and negative for Pseudomonas aeruginosa. First and multiple event analyses were used to investigate risk factors for pulmonary exacerbations.
We evaluated a total of 5129 PEx from 1734 CF patients in the EPIC study. Multiple event analysis identified 2 more factors associated with occurrence of PEx compared to first event analysis. After adjusting for multiple factors, the following were associated with higher occurrence of PExs: female gender, older age at enrollment, household cigarette smoke exposure, increased cough at the most recent encounter, having used antibiotics since the previous encounter, a positive culture for any CF organism at the most recent encounter, and having had a PEx in the last 30 days.
Multiple event analyses use all PEx events and may identify more risk factors for PEx than analysis of time to first PEx. We have provided an example of how to apply this type of analysis and how to interpret estimates in the context of the EPIC study.
肺部加重（PEx）是囊性纤维化（CF）患者发病和死亡的重要因素。了解PEx的危险因素对于改善治疗至关重要；肺部加重也是CF临床试验的一项重要指标。目前的风险评估通常仅评估首次发生PEx的时间。考虑观察期内多次加重情况的方法可能更有助于检测出显著的危险因素。
早期铜绿假单胞菌感染控制（EPIC）观察性研究纳入了2004年至2006年间年龄≤12岁且铜绿假单胞菌检测呈阴性的参与者。采用首次事件分析和多次事件分析来研究肺部加重的危险因素。
在EPIC研究中，我们共评估了1734例CF患者的5129次PEx。与首次事件分析相比，多次事件分析确定了另外2个与PEx发生相关的因素。在对多个因素进行调整后，以下因素与PEx的较高发生率相关：女性、入组时年龄较大、家庭中有香烟烟雾暴露、最近一次就诊时咳嗽增加、自上次就诊后使用过抗生素、最近一次就诊时任何CF病原体培养呈阳性以及在过去30天内发生过PEx。
多次事件分析使用了所有PEx事件，与分析首次PEx发生时间相比，可能会识别出更多PEx的危险因素。我们提供了一个如何应用此类分析以及如何在EPIC研究背景下解释评估结果的示例。
