Endothelial injury and decline in lung function in persons living with HIV: a prospective Danish cohort study including 698 adults

OBJECTIVES: Endothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea.

METHODS: A prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model.

RESULTS: We did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: -3.9-12.9, p = 0.30), TM: 2.2 mL/year (95% CI: -6.0-10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: -6.0-14.2, p = 0.42), TM: 1.4 mL/year (95% CI: -8.3-11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89-2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65-1.71, p = 0.26).

CONCLUSION: We did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.