Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Abstract

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-α), 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-α, 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.

Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals

“…Spirometric results were normal on average with a median (IQR) postbronchodilator FEV 1 % predicted of 98 (88-109); however, diffusing capacity was low on average with a median (IQR) DL CO % predicted of 69 (57-81). The median (IQR) percentage of voxels , -910 HU was 7 (3-16), WA% was 46 (42-49), tricuspid regurgitation velocity was 2.4 (2.2-2.6), and estimated pulmonary artery systolic pressure was 33 (29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation

“…whipplei . However, we chose these inflammatory markers because studies have shown that plasma levels of these cytokines are negatively associated with lung function in HIV-infected individuals [ 16 , 17 ]. In this cohort, 93.4% participants received ART, median CD4 + cell count was more than 600 cells/μl, and median plasma HIV viral load was about 100 copies per ml.…”

HIV Infection, Pulmonary Tuberculosis, and COPD in Rural Uganda: A Cross-Sectional Study

“…PLWH are more susceptible to mycobacterial infection, particularly in TB-endemic regions such as SSA[12]. Tuberculosis increases the risk of COPD through several mechanisms, including infection-related parenchymal scarring and chronic airways inflammation from latently-infected pulmonary macrophages[25–27]. HIV itself may also directly cause COPD through the consequences of HIV-infected pulmonary macrophages, which lead to alveolar inflammation, epithelial barrier dysfunction, altered pulmonary oxidant-antioxidant balance, increased cellular apoptosis and altered respiratory tract microbial colonization, all of which are implicated in COPD pathogenesis[28–31].…”

“…HIV itself may also directly cause COPD through the consequences of HIV-infected pulmonary macrophages, which lead to alveolar inflammation, epithelial barrier dysfunction, altered pulmonary oxidant-antioxidant balance, increased cellular apoptosis and altered respiratory tract microbial colonization, all of which are implicated in COPD pathogenesis[28–31]. Indeed, HIV-associated systemic biomarkers of inflammation and immune activation, which persist despite viral suppression, have been associated with pulmonary dysfunction[26,27]. Associations between tuberculosis and COPD among PLWH in North American cohorts have not been described, possibly related to lower tuberculosis prevalence.…”