Systemic inflammatory networks in HIV-associated chronic obstructive pulmonary disease.
OBJECTIVES People living with HIV (PLWH) carry increased risk of chronic obstructive pulmonary disease (COPD), yet the underlying mechanisms remain poorly understood. We investigated whether systemic inflammatory profiles differ between PLWH with and without COPD. METHODS We analyzed serum samples from 87 PLWH: 38 with COPD and 49 without COPD, matched for age and sex. Inflammatory proteins were measured using the Olink Target 96 Inflammation panel. Modules of co-varying analytes were identified using CytoMod, and associations with clinical features were tested. Key findings were validated using ELISA. A replication analysis was conducted in 158 samples from an independent cohort. RESULTS PLWH with COPD showed significantly elevated inflammatory markers. CytoMod analysis identified five modules when adjusting for background levels. Two modules were significantly associated with COPD, and comprised molecules involved in tissue damage and repair. Individual molecules including PD-L1, FGF-23, IL6, and others were significantly dysregulated. ELISA validation confirmed significantly elevated levels of IL-10RB, PD-L1, M-CSF, and IL-6 in PLWH-COPD. Key analytes and directional effects were confirmed in an independent cohort. CONCLUSIONS PLWH with COPD exhibit distinct inflammatory signatures characterized by enhanced tissue damage, immune activation, and dysregulated repair mechanisms, providing insights into HIV-related COPD.