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

Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (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 individuals 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 4 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 4 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 4 was 0.32. Higher variability participants had higher St George's Respiratory Questionnaire (SGRQ) scores (47.3 +/- 20.3 versus 39.6 +/- 21.5, p=.04) than lower variability participants. Exploratory analyses found no relationship between symptom variability and health care resource utilization-defined 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.

Automated summary

This study compares different statistical measures of symptom variability in patients with chronic obstructive pulmonary disease (COPD) and identifies characteristics of individuals with higher symptom variability. The within-subject standard deviation (WS-SD) method is found to be a useful measure of symptom variability and is associated with worse health-related quality of life in COPD patients.