Virchow J Christian, Backer Vibeke, de Blay Frédéric, Kuna Piotr, Ljørring Christian, Prieto Jesus L, Villesen Hanne H
Department of Pneumology/Intensive Care Medicine, Zentrum für Innere Medizin, Klinik I, Universitätsklinikum Rostock, Germany.
Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen University, Denmark.
Respir Med. 2015 May;109(5):547-56. doi: 10.1016/j.rmed.2015.01.012. Epub 2015 Feb 3.
Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition is needed for use in clinical trials.
Focussing on moderate exacerbations, this opinion piece reviews landmark trials and current guidelines to provide a practical definition of a moderate exacerbation. Specifically, we adapt the ATS/ERS consensus statement of terminology Reddel et al. (2009) [1] which provides a conceptual (or 'theoretical') definition for moderate exacerbations, to an operational (or 'practical') criterion suitable for use in clinical research.
The proposed definition for a moderate exacerbation requires ≥1 of the following criteria combined with a change in treatment: a) nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights or an increase of ≥0.75 from baseline in daily symptom scores on 2 consecutive days; b) increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase: 4 puffs/day); c) ≥20% decrease in PEF from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline and/or d) visit to the emergency room/trial site for asthma treatment not requiring systemic corticosteroids.
A clinically and patient-relevant, operational definition of moderate exacerbations is needed. The proposed definition has been endorsed by the EMA Scientific Advice Working Party in 2011and needs to be trialled in forthcoming clinical studies.
急性加重是临床研究的关键结果，可提供有关症状控制、健康状况和疾病进展的患者相关信息。通常被视为呼吸道症状的（亚）急性恶化发作，在临床试验中需要一个精确且临床有用的定义。
本文聚焦于中度急性加重，回顾了具有里程碑意义的试验和当前指南，以提供中度急性加重的实用定义。具体而言，我们将Reddel等人（2009年）[1]的美国胸科学会/欧洲呼吸学会术语共识声明中为中度急性加重提供的概念性（或“理论性”）定义，改编为适用于临床研究的操作性（或“实用性”）标准。
提出的中度急性加重定义要求以下标准中的≥1项并伴有治疗改变：a）因哮喘导致夜间觉醒，连续2晚需要使用短效β2受体激动剂（SABA），或连续2天每日症状评分较基线增加≥0.75；b）连续2天SABA使用次数较基线增加（最小增加量：4喷/天）；c）至少连续2个早晨/晚上呼气峰流速（PEF）较基线下降≥20%，或第1秒用力呼气容积（FEV1）较基线下降≥20%，和/或d）因哮喘治疗前往急诊室/试验点，但不需要全身使用糖皮质激素。
需要一个临床相关且针对患者的中度急性加重操作性定义。该提议定义已在2011年得到欧洲药品管理局科学建议工作组的认可，需要在即将开展的临床研究中进行试验。
