ABSTRACT
OBJECTIVE: Chronic obstructive pulmonary disease is a common comorbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other comorbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. DESIGN: Longitudinal observational study. METHODS: Total 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, and TNFα), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. RESULTS: In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse forced expiratory volume in one second (FEV1) percentage-predicted, and higher sCD163 associated with worse FEV1/forced vital capacity. IL-6, TNFα, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. CONCLUSION: Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of chronic obstructive pulmonary disease in HIV-infected persons.