Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough

Purpose: Objective cough frequency is used to assess efficacy of chronic cough (CC) treatments. The objective of this study was to explore the relationship between objective cough frequency and cough-specific patient-reported outcomes (PROs) and estimate a clinically meaningful change threshold (MCT) for objective cough frequency.

Methods: Data collected in a phase 2b study in participants with refractory or unexplained CC were used to investigate the relationship between 24-h cough frequency (measured using an ambulatory cough monitor) and cough-specific PROs (i.e., cough severity visual analog scale, cough severity diary, Leicester Cough Questionnaire). Convergent validity was assessed using Spearman ρ. An MCT for 24-h cough frequency was estimated using the patient global impression of change (PGIC) scale as an anchor.

Results: Correlations between 24-h cough frequency and cough-specific PROs at baseline, Week 4, and Week 12 were significant (P < 0.0001) but low to moderate in strength (ρ = 0.30-0.58). Participants categorized as very much improved/much improved (i.e., PGIC of 1 or 2) or minimally improved (i.e., PGIC of 3) had mean 24-h cough frequency reductions of 55% and 30%, respectively. Receiver operating characteristic curve analysis suggested that a 24-h cough frequency reduction of 38% optimizes sensitivity and specificity for predicting a PGIC score of 1-3.

Conclusion: Objective 24-h cough frequency is significantly associated with cough-specific PROs, but cough frequency and PROs most likely capture distinct aspects of CC. A ≥ 30% reduction in 24-h cough frequency is a reasonable MCT to define treatment response in CC clinical trials.