Abstract
BackgroundCOPD 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.ObjectiveTo determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals.MethodsAssociations 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.ResultsAmong 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.ConclusionsThis 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.
Highlights
Our findings suggest the pathogenesis of HIV-associated Chronic obstructive pulmonary disease (COPD) may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco
P < 0.05 § P 0.10 Abbreviations: post-BD = post-bronchodilator; BMI = body mass index; CAT = COPD Assessment Test; CC16 = club cell secretory protein-16; DLco%predicted = diffusing capacity for carbon monoxide corrected as percentage of predicted reference value; FEV1%predicted = forced expiratory volume in 1 second as percentage of predicted reference value; FEV1/FVC ratio = ratio of forced expiratory volume in 1 second to forced vital capacity; FVC%predicted = forced vital capacity as percentage of predicted reference value; PARC/CCL-18 = pulmonary and activation-regulated chemokine; SP-D = surfactant protein-D; soluble receptor for advanced glycation end-products (sRAGE) = soluble receptor for advanced glycation endproducts
We found that higher PARC/CCL-18 levels and higher cell secretory protein-16 (CC-16) levels were significantly associated with lower DLco%predicted
Summary
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
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