Objective
Chronic obstructive pulmonary disease (COPD) is a common co-morbidity 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 co-morbidities, 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
274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, TNF-伪), 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 FEV1 percent-predicted, and higher sCD163 associated with worse FEV1/FVC. IL-6, TNF-伪, 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.
Conclusions
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 COPD in HIV-infected persons.