Cumulative loneliness, loneliness trajectories, and chronic lung disease in multinational cohorts: the role of depressive symptoms

Loneliness has become an important public health concern among middle-aged and older adults, and evidence suggests it may be associated with chronic lung disease (CLD). However, whether cumulative exposure to loneliness is related to CLD across national settings remains unclear. This study analyzed four nationally representative longitudinal cohorts. Cumulative loneliness was defined as the number of waves with loneliness across three time points. Cox proportional hazards models and random-effects meta-analysis were used to examine the association between cumulative loneliness and incident CLD. Multiple sensitivity analyses were further performed. Mediation analysis assessed whether depressive symptoms contributed to this association. A total of 19,229 participants were included, with median follow-up ranging from 4.1 to 7.3 years across cohorts. Compared with participants who never experienced loneliness, those who experienced loneliness at three time points had a significantly higher risk of incident CLD in each cohort and in the pooled analysis after full adjustment. Cohort-specific associations varied among participants who reported loneliness at one or two time points. Multiple sensitivity analyses, including group-based trajectory modeling (GBTM), generally supported the robustness of findings. Mediation analyses suggested that depressive symptoms may partially mediate the association in ELSA, CHARLS, and the pooled analysis. Our findings indicate that cumulative loneliness was linked to higher incident CLD risk among middle-aged and older adults across four national settings. Depressive symptoms may partially mediate this association. Targeted loneliness monitoring and interventions may help reduce CLD risk in aging populations.