Characterizing COPD Symptom Variability in the Stable State Utilizing the Evaluating Respiratory Symptoms in COPD Questionnaire.

Rationale It has been suggested that patients with COPD experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day symptom variability. Objectives To compare standard deviation with other statistical measures of symptom variability and identify characteristics of subjects with higher symptom variability. Methods Individuals in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) Exacerbations sub-study completed an Evaluating Respiratory Symptoms in COPD (E-RS) daily questionnaire. We calculated within-subject standard deviation (WS-SD) for each patient at week 0 and correlated this with measurements obtained four weeks later using Pearson's r and Bland Altman plots. Median WS-SD value dichotomized participants into higher versus lower variability groups. Association between WS-SD and exacerbation risk during four follow up weeks was explored. Measurements and Main Results Diary completion rates were sufficient in 140 (68%) of 205 sub-study participants. Reproducibility (r) of the WS-SD metric from baseline to week four was 0.32. Higher variability participants had higher St. George's Respiratory Questionnaire (SGRQ) scores (47.3 ± 20.3 vs 39.6 ± 21.5, p=.04) than lower variability participants. Exploratory analyses found no relationship between symptom variability and HCRU exacerbations. Conclusions WS-SD of the E-RS can be used as a measure of symptom variability in studies of patients with COPD. Patients with higher variability have worse health-related quality of life. WS-SD should be further validated as a measure to understand the implications of symptom variability.