Defining moderate asthma exacerbations in clinical trials based on ATS/ERS joint statement

Abstract

Background: 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.

Aim and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Asthma; Asthma control; Clinical trial; Moderate exacerbations.