Abstract

Introduction: Chronic 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). Methods: We 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 mixedeffects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. Results: We 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). Conclusions: There 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.

Original languageEnglish (US)
Article numbere000180
JournalBMJ Open Respiratory Research
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2017

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Sphingolipids
Chronic Obstructive Pulmonary Disease
HIV
Tryptophan
Kynurenine
Mass Spectrometry
Metabolomics
Diglycerides
Liquid Chromatography
Biomarkers
Smoking

Cite this

@article{74ccdd29a9a64226b2895cb6afc51851,
title = "Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease",
abstract = "Introduction: Chronic 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). Methods: We 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 mixedeffects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. Results: We 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). Conclusions: There 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.",
author = "Shane Hodgson and Griffin, {Timothy J} and Reilly, {Cavan S} and Harvey, {Stephen B} and Witthuhn, {Bruce A} and Sandri, {Brian J} and Kunisaki, {Ken M} and Wendt, {Christine H}",
year = "2017",
month = "1",
day = "1",
doi = "10.1136/bmjresp-2017-000180",
language = "English (US)",
volume = "4",
journal = "BMJ Open Respiratory Research",
issn = "2052-4439",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease

AU - Hodgson, Shane

AU - Griffin, Timothy J

AU - Reilly, Cavan S

AU - Harvey, Stephen B

AU - Witthuhn, Bruce A

AU - Sandri, Brian J

AU - Kunisaki, Ken M

AU - Wendt, Christine H

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Introduction: Chronic 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). Methods: We 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 mixedeffects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. Results: We 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). Conclusions: There 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.

AB - Introduction: Chronic 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). Methods: We 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 mixedeffects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. Results: We 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). Conclusions: There 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.

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U2 - 10.1136/bmjresp-2017-000180

DO - 10.1136/bmjresp-2017-000180

M3 - Article

C2 - 28409005

AN - SCOPUS:85032351552

VL - 4

JO - BMJ Open Respiratory Research

JF - BMJ Open Respiratory Research

SN - 2052-4439

IS - 1

M1 - e000180

ER -