Social isolation and mortality in chronic obstructive pulmonary disease: Evidence from 1999 to 2018 NHANES with mediation by systemic inflammation

This study aimed to investigate the association between social isolation and mortality risk in U.S. adults with chronic obstructive pulmonary disease (COPD) and to explore the potential mediating role of systemic inflammation. We conducted a retrospective cohort study of adults with COPD from the 1999 to 2018 National Health and Nutrition Examination Survey. The associations between social isolation and mortality risks from all-cause, cardiovascular disease (CVD), and chronic lower respiratory disease (CLRD) were assessed using Cox proportional hazards models by reporting hazard ratios and 95% confidence intervals. Mediation analyses were performed to assess the contributions of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Among 1726 participants (mean age 65.29 years; 50.97% women) included, the prevalence of social isolation was 15.47%. Over a median follow-up of 83 months, 709 deaths occurred. Socially isolated participants demonstrated significantly increased mortality risks, with fully adjusted hazard ratios (95% confidence intervals) of 1.59 (1.22-2.08) for all-cause, 2.66 (1.64-4.32) for CVD, and 1.86 (1.13-3.05) for CLRD mortality, compared to nonisolated participants. Population-attributable fraction analyses indicated that social isolation was associated with 13.2% of all-cause, 24.2% of CVD, and 16.5% of CLRD deaths. Mediation analysis revealed that neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio explained 6.32% to 13.15% and 4.78% to 7.75% of these associations, respectively. Social isolation is independently associated with a significantly elevated mortality risk in U.S. adults with COPD, partially mediated by systemic inflammation. These findings highlight the potential clinical and public health importance of addressing social isolation to improve survival in COPD patients.