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

ABSTRACT: 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.

SUBMITTER: Jeon D

PROVIDER: S-EPMC6772133 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Jeon Diane D Chang Emily G EG McGing Maggie M Hartman-Filson Marlena M Sommers Mathew M Lewis Eula E Balmes John R JR Moisi Daniela D Lederman Michael M MM Madsen Kristine A KA Woodruff Prescott G PG Hunt Peter W PW Huang Laurence L

PloS one 20191001 10

<h4>Background</h4>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.<h4>Objective</h4>To determine whether these pneumoprot ...[more]

PMID: 31574118

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Project description: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.Longitudinal observational study.Total 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, and TNF?), 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.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, TNF?, 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.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.

Project description:Background: HIV-infected individuals have increased risk of developing obstructive lung disease (OLD). Studies from developed countries report high viral load, low CD4 counts, and anti-retroviral therapy (ART) to be associated with OLD; but these findings may not be generalizable to populations in resource-limited settings.Methods: We conducted a prospective cohort study of lung function in 730 HIV-infected black South African adults. Pre-bronchodilator spirometry was performed at enrollment and repeated annually for three years. Logistic regression models were used to identify factors associated with OLD, defined as FEV1/FVC<0.70, at enrollment. Excess annual declines in FEV1 and FVC were modelled as the product-term of follow-up time and exposures using random effects regression.Results: Median (IQR) age at enrollment was 36 (32-41) years, 85% were female and 30% ever-smoked with a median (IQR) exposure of 3 (1-6) pack-years. Median (IQR) CD4 count and viral load at enrollment were 372 (261-518) cells/mm3 and 2655 (91-13,548) copies/mL respectively. Overall, 25% were receiving ART at enrollment, 16% of whom reported at least 6 months of ART receipt. OLD was found in 35 (5%) at enrollment. Increasing age (aOR = 2.08 per 10-years [95%CI 1.22-3.57], p = 0.007), current smoking (aOR = 3.55 [95%CI 1.20-10.53], p = 0.02), and CRP (aOR = 1.01 per unit-increase [95%CI 1.00-1.03], p = 0.04) were significantly associated with OLD at enrollment; while increasing CD4 count (aOR = 1.02 per-100 cells/mm3 [95%CI 0.85-1.22], p = 0.82), viral load (aOR = 0.67 per log-increase [95%CI 0.43-1.10], p = 0.12) and receipt of ART (aOR = 0.57 [95%CI 0.18-1.75], p = 0.32) were not. The median (IQR) follow-up time was 18 (12-24) months. Participants with a history of tuberculosis (TB) had a 35 mL (95%CI 2-68, p = 0.03) and 57 mL (95%CI 19-96, p = 0.003) per year excess loss of FEV1 and FVC respectively.Conclusion: Prevalent OLD was associated with older age, current smoking and higher CRP levels, but not CD4 counts and ART, in HIV-infected South African adults. Better understanding of the long-term effects of TB, smoking and inflammation on lung function in HIV-infected populations is urgently needed.

Dataset Information

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

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

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