TY - JOUR
T1 - Lung and Plasma Metabolome in HIV-Associated Obstructive Lung Disease
AU - Wendt, Chris H.
AU - Samorodnitsky, Sarah
AU - Lock, Eric F.
AU - Kruk, Monica
AU - Morris, Alison
AU - Leung, Janice M.
AU - Kunisaki, Ken M.
AU - Griffin, Timothy J.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background:HIV is a risk factor for obstructive lung disease (OLD), independent of smoking. We used mass spectrometry (MS) approaches to identify metabolomic biomarkers that inform mechanistic pathogenesis of OLD in persons with HIV (PWH).Methods:We obtained bronchoalveolar lavage fluid (BALF) samples from 52 PWH, in case:control (+OLD/-OLD) pairs matched on age, smoking status, and antiretroviral treatment. Four hundred nine metabolites from 8 families were measured on BALF and plasma samples using a MS-based Biocrates platform. After filtering metabolites with a high proportion of missing values and values below the level of detection, we performed univariate testing using paired t tests followed by false discovery rate corrections. We used distance-weighted discrimination (DWD) to test for an overall difference in the metabolite profile between cases and controls.Results:After filtering, there were 252 BALF metabolites for analysis from 8 metabolite families. DWD testing found that collectively, BALF metabolites differentiated cases from controls, whereas plasma metabolites did not. In BALF samples, we identified 3 metabolites that correlated with OLD at the false discovery rate of 10%; all were in the phosphatidylcholine family. We identified additional BALF metabolites when analyzing lung function as a continuous variable, and these included acylcarnitines, triglycerides, and a cholesterol ester.Conclusions:Collectively, BALF metabolites differentiate PWH with and without OLD. These included several BALF lipid metabolites. These findings were limited to BALF and were not found in plasma from the same individuals. Phosphatidylcholine, the most common lipid component of surfactant, was the predominant lipid metabolite differentially expressed.
AB - Background:HIV is a risk factor for obstructive lung disease (OLD), independent of smoking. We used mass spectrometry (MS) approaches to identify metabolomic biomarkers that inform mechanistic pathogenesis of OLD in persons with HIV (PWH).Methods:We obtained bronchoalveolar lavage fluid (BALF) samples from 52 PWH, in case:control (+OLD/-OLD) pairs matched on age, smoking status, and antiretroviral treatment. Four hundred nine metabolites from 8 families were measured on BALF and plasma samples using a MS-based Biocrates platform. After filtering metabolites with a high proportion of missing values and values below the level of detection, we performed univariate testing using paired t tests followed by false discovery rate corrections. We used distance-weighted discrimination (DWD) to test for an overall difference in the metabolite profile between cases and controls.Results:After filtering, there were 252 BALF metabolites for analysis from 8 metabolite families. DWD testing found that collectively, BALF metabolites differentiated cases from controls, whereas plasma metabolites did not. In BALF samples, we identified 3 metabolites that correlated with OLD at the false discovery rate of 10%; all were in the phosphatidylcholine family. We identified additional BALF metabolites when analyzing lung function as a continuous variable, and these included acylcarnitines, triglycerides, and a cholesterol ester.Conclusions:Collectively, BALF metabolites differentiate PWH with and without OLD. These included several BALF lipid metabolites. These findings were limited to BALF and were not found in plasma from the same individuals. Phosphatidylcholine, the most common lipid component of surfactant, was the predominant lipid metabolite differentially expressed.
KW - HIV
KW - OLD
KW - biomarker
KW - bronchoalveolar lavage
KW - metabolome
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U2 - 10.1097/QAI.0000000000003061
DO - 10.1097/QAI.0000000000003061
M3 - Article
C2 - 35849661
AN - SCOPUS:85140274188
SN - 1525-4135
VL - 91
SP - 312
EP - 318
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 3
ER -