Circulating markers of organ damage associate with COPD in people with HIV: an exploratory proteomic analysis

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BACKGROUND: People with HIV (PWH) develop chronic obstructive pulmonary disease (COPD) more frequently and at younger ages than the general population, yet the circulating proteomic correlates of COPD in PWH remain poorly characterized. METHODS: We applied a targeted 92-plex organ damage proteomics panel (Olink Organ Damage) to compare serum protein profiles between 38 PWH with established COPD and 49 PWH without COPD, enrolled in a prospective observational cohort. RESULTS: Differential abundance analysis adjusted for age, sex, BMI, and current smoking status identified several proteins (NUCB2, ALDH3A1, CLEC1A, CALCA, BAMBI, PGF) significantly elevated in PWH with COPD after correction for multiple testing, with several additional proteins reaching nominal significance only. Using a repeated nested cross-validated LASSO framework, a proteomic model achieved modest discriminatory performance (area under the curve, AUC 0.67), comparable to a routine laboratory model (AUC 0.74). A clinical model incorporating FEV1 achieved higher discrimination (AUC 0.84), though this comparison is limited by the partial construct overlap with the GOLD-based COPD definition. Notably, the proteomic model showed statistically significant incremental discriminative value over a spirometry-free clinical model (age, sex, BMI, smoking status; AUC 0.47), suggesting the proteomic signature captures COPD-relevant biological information beyond demographics and smoking history. A stacked meta-model combining all modalities did not significantly outperform the FEV1-inclusive clinical model (AUC 0.87). CONCLUSIONS: Our findings provide exploratory evidence for candidate circulating organ damage markers of COPD in PWH and provide a basis for further studies into the mechanisms and immunopathology of this comorbidity, including studies in larger cohorts with HIV-negative comparator groups.

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