Markers of inflammation and immune activation are associated with lung function in a multi-center cohort of persons with HIV.

OBJECTIVES: Studies have shown that people with HIV (PWH) may be at increased risk for chronic lung diseases and lung function abnormalities, which may be associated with immune activation. We tested the association of a panel of 12 immune activation and inflammation biomarkers with spirometry and single-breath diffusing capacity for carbon monoxide (DLco). DESIGN: Cross-sectional, observational study. METHODS: Participants were enrolled from the Inflammation, Aging, Microbes and Obstructive Lung Disease cohort of PWH at two US sites. Biomarkers were examined and standardized spirometry and DLco testing were performed. We tested associations between each biomarker and lung function, examined individually and in combination, using multi-variable linear and logistic regression. RESULTS: Among 199 participants, median forced expiratory volume in 1 s (FEV1) was normal (90% predicted) and median DLco was abnormal (69% predicted). The most common lung function abnormality (57%) was a normal FEV1 to forced vital capacity ratio with an abnormal DLco of 80% or less predicted (iso↓DLco). Two markers (IL-6, high-sensitivity C-reactive protein) were associated with FEV1% predicted, whereas eight markers (soluble CD14, soluble CD163, inducible protein-10, soluble CD27, IL-6, soluble tumor necrosis factor receptors 1 and 2, D-dimer) were associated with DLco% predicted. Compared with those participants with normal spirometry and DLco, five markers (soluble CD14, soluble CD163, interferon gamma inducible protein-10, soluble tumor necrosis factor receptors 1 and 2) were associated with iso↓DLco. CONCLUSION: Among PWH, different markers of immune activation and inflammation are associated with FEV1% predicted than with DLco% predicted and with an iso↓DLco, representing possible unique pathways of chronic lung disease. Identifying plausible drivers of these inflammatory pathways may clarify mechanisms underlying impaired lung function in HIV infection and may identify therapeutic avenues.

Pneumoproteins are associated with pulmonary function in HIV-infected persons.

BACKGROUND: COPD is a common HIV comorbidity, and HIV-infected individuals have a higher incidence and earlier onset of COPD compared to HIV-uninfected individuals. While the pathogenesis of HIV-associated COPD is largely unknown, chronic inflammation may contribute. Four pneumoproteins known to be markers of lung injury and inflammation have been associated with COPD in HIV-uninfected individuals: PARC/CCL-18, SP-D, CC-16, and sRAGE. OBJECTIVE: To determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals. METHODS: Associations between plasma pneumoprotein levels and pulmonary function were determined in a cross-sectional study of otherwise healthy HIV-infected individuals enrolled between September 2016 and June 2017. Covariates included HIV-associated (antiretroviral therapy, CD4 count, and viral load) and COPD-associated (smoking and BMI) covariates. RESULTS: Among 65 participants, 78.5% were male, 50.8% had undetectable viral load, and 76.9% were ever-smokers. Mean post-bronchodilator FEV1/FVC was 0.71, and mean DLco%predicted was 61%. Higher PARC/CCL-18 was associated with lower DLco%predicted and higher CAT score. Higher CC-16 was associated with lower DLco%predicted and lower FVC%predicted. CONCLUSIONS: This exploratory analysis is the first to characterize associations between these four pneumoproteins and pulmonary function in an HIV-infected cohort. Our findings suggest the pathogenesis of HIV-associated COPD may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco. PARC/CCL-18 is associated with structural and functional pulmonary abnormalities and may be an important COPD biomarker candidate in HIV infection. Our study is a preliminary step toward finding clinically relevant COPD biomarkers in high-risk populations.