Abstract
BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) are disproportionately affected by social determinants of health that have been associated with worse respiratory outcomes. This study evaluates the association of perceived stress with respiratory outcomes and distinct biological mechanisms among former smokers with COPD. METHODS: Participants were assessed in an observational study at baseline, 3-months, and 6-months. Questionnaires assessed perceived stress (Perceived Stress Scale, [PSS]), respiratory symptoms, and incidence of COPD exacerbations. Generalized linear mixed models evaluated the association of PSS score with COPD outcomes and biomarkers of platelet activation (urine 11-dehydro-thromboxane B2 [11dTxB2]), oxidative stress (urine thiobarbituric acid reactive substances [TBARS], 8- hydroxydeoxyguanosine, and 8-isoprostane), and inflammation. RESULTS: Among 99 participants, the median PSS score was 13 (interquartile range 8-18) across all visits. Compared with low perceived stress (PSS 0-13), moderate (PSS 14-26) and high perceived stress (PSS 27-40) were associated with worse respiratory health status and respiratory-related quality of life, with point estimates for high perceived stress exceeding clinically important differences. Only high PSS was associated with increased moderate/severe exacerbations (odds ratio 4.15, 95% confidence interval [CI]: 1.28-13.47). Compared to low stress, high stress was associated with lower TBARS (β=-25.5%, 95%CI: -43.8- -1.2%) and higher 8-isoprostane (β=40.1%, 95%CI: 11.5-76.0%). Among individuals with mild-moderate COPD, compared to low stress, moderate (β=20.1%, 95%CI: 3.1-40.0%) and high (β=52.9%, 95%CI: 22.1-91.6%) stress were associated with higher 11dTxB2. CONCLUSION: Among former smokers with COPD, higher perceived stress is associated with worse respiratory outcomes. Platelet activation and oxidative stress may be biological pathways through which perceived stress plays a role in COPD.