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.