Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease

Abstract

IntroductionChronic obstructive pulmonary disease (COPD) is a significant cause of morbidity in persons living with HIV (PLWH) and HIV appears to uniquely cause COPD, independent of smoking. The mechanisms by which HIV leads to COPD are not clear. The objective of this study was to identify metabolomic biomarkers and potential mechanistic pathways of HIV-associated COPD (HIV-COPD).MethodsWe performed case–control metabolite profiling via mass spectrometry in plasma from 38 individuals with HIV-COPD (cases), comparing to matched controls with/without HIV and with/without COPD. Untargeted metabolites of interest were identified with liquid chromatography with mass spectrometry (LC-MS/mass spectrometry (MS)), and targeted metabolomics for tryptophan (Trp) and kynurenine (Kyn) were measured by selective reaction monitoring (SRM) with LC-MS/MS. We used mixed-effects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables.ResultsWe identified 1689 analytes associated with HIV-COPD at a false discovery rate (FDR) of 10%. In PLWH, we identified 263 analytes (10% FDR) between those with and without COPD. LC MS/MS identified Trp and 17 lipids, including sphingolipids and diacylglycerol. After adjusting for relevant covariates, the Kyn/Trp ratio measured by SRM was significantly higher in PLWH (p=0.022), but was not associated with COPD status (p=0.95).ConclusionsThere is a unique metabolite profile in HIV-COPD that includes sphingolipids. Trp metabolism is increased in HIV, but does not appear to independently contribute to HIV-COPD.Trial registration numbersNCT01810289, NCT01797367, NCT00608764.

Associations between baseline biomarkers and lung function in HIV-positive individuals

“…In a small case-control study from the START pulmonary substudy that included 38 HIV-positive individuals with COPD compared to 40 HIV-positive individuals without COPD, we also identified a unique metabolite profile in HIV-associated COPD that included sphingolipids. [31] We have not measured sphingolipids more broadly in our START pulmonary substudy cohort.…”

Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and Inflammation

“…Metabolite profiling has also been performed in plasma of individuals with HIV-COPD. PLWH and COPD had a metabolite profile that included sphingolipids and fatty acids (132). Tryptophan metabolism was also altered in HIV, but was not associated with HIV-COPD.…”

Functions of Sphingolipids in Pathogenesis During Host–Pathogen Interactions

“…In addition, HIV-chronic obstructive pulmonary disease (HIV-COPD) exhibits a unique plasma metabolome profile that includes sphingolipids and fatty acids. However, additional studies are needed to determine how such metabolic pathways contribute to HIV-COPD and whether therapeutic interventions to alter sphingolipid biosynthesis may reduce the risk of COPD ( Hodgson et al, 2017 ).…”