title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pneumology/Intensive Care Medicine, Zentrum für Innere Medizin, Klinik I, Universitätsklinikum Rostock, Germany. Electronic address: j.c.virchow@med.uni-rostock.de.
authors: J Christian
authors: JC
authors: Virchow
authors: Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen University, Denmark.
authors: Vibeke
authors: V
authors: Backer
authors: Chest Diseases Department, University Hospital of Strasbourg, Federation of Translational Medicine of Strasbourg, Strasbourg University, Strasbourg, France.
authors: Frédéric
authors: F
authors: de Blay
authors: Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Lodz, Poland.
authors: Piotr
authors: P
authors: Kuna
authors: Global Clinical Development, ALK, Bøge Allé 1, DK 2970 Hørsholm, Denmark.
authors: Christian
authors: C
authors: Ljørring
authors: Department of Medicine, University of Valencia, Valencia, Spain.
authors: Jesus L
authors: JL
authors: Prieto
authors: Global Clinical Development, ALK, Bøge Allé 1, DK 2970 Hørsholm, Denmark.
authors: Hanne H
authors: HH
authors: Villesen
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy; D018450:Disease Progression; D004636:Emergency Service, Hospital; D006801:Humans; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents
keywords: Asthma; Asthma control; Clinical trial; Moderate exacerbations