An Endpoint for Worsening Asthma: Development of a Sensitive Measure and its Properties *

Abstract

The measurement of clinical efficacy in asthma lacks a validated endpoint for worsening asthma outcome. We propose a standard measure of worsening asthma and investigate its measurement characteristics. Data from two clinical trials were used to develop a composite endpoint that incorporated the following parameters on any study day: (1) decrease from baseline in peak expiratory flow (PEF) of >20%; (2) increase above baseline in β-agonist use of >70% (≥2 puffs/day); (3) increase above baseline in symptom score of >50%; (4) >2 nighttime awakenings; (5) PEF <180 L/min (adults); or (6) oral corticosteroid rescue or unanticipated visits to the physician, emergency room, or hospital. This novel endpoint demonstrated sufficient test/retest reliability (p = 0.67), prospectively exhibited a dose-response profile consistent with different dose levels of mon-telukast (a leukotriene antagonist), and was significantly correlated with forced expiratory volume in one second, quality of life, and global evaluations. The endpoint appears to be a valid and sensitive measure of day-to-day worsening of asthma and is appropriate for use in clinical trials.