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Pneumonia-Specific Plasma Metabolite Profiles Among Patients Hospitalized with Infection in Southeast Asia

32 Pages Posted: 4 Jun 2024

See all articles by Taylor D. Coston

Taylor D. Coston

University of Washington

Lu Xia

Michigan State University

Shelton W. Wright

University of Washington

Viriya Hantrakun

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit

Parinya Chamnan

Sunpasitthiprasong Hospital

Gumphol Wongsuvan

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit

Rungnapa Phunpang

Mahidol University

Adul Dulsuk

Mahidol University

Ekkachai Thiansukhon

Sunpasitthiprasong Hospital

Ali Shojaie

University of Washington

Narisara Chantratita

Mahidol University

Direk Limmathurotsakul

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit

Sina A. Gharib

University of Washington

T. Eoin West

University of Washington

More...

Abstract

Background: Community-acquired pneumonia (CAP) is a major public health threat globally but is understudied in regions with the highest burden. The host immune response during infection may differ based on the site of infection. We hypothesized that analysis of the plasma metabolome in patients hospitalized with suspected infection could identify host response pathways specific to CAP.

Methods: We analyzed the plasma metabolomes of adults admitted to a tertiary care hospital in northeastern Thailand with suspected community-acquired infection. Multivariable linear regression was performed for differential metabolite analyses and globaltest was used for pathway analysis comparing patients with CAP vs. non-CAP infections and uninfected controls. Least absolute shrinkage and selection operator (LASSO) was used to identify a parsimonious metabolite prognostic signature that was tested on an internal validation set to predict mortality.

Findings: Eight hundred forty-one metabolites from 107 CAP patients and 152 non-CAP infected patients were analyzed. Forty-nine metabolites were differentially abundant between the CAP and non-CAP groups. CAP was characterized by increased metabolites involved in Polyamine metabolism and decreased metabolites involved in lipid pathways. Ten pathways were differentially enriched between the CAP and non-CAP groups consistent with individual metabolite analyses. Thirty-nine metabolites and three pathways were associated with CAP-specific mortality. A four-metabolite signature predicted 28-day mortality in CAP (AUC 0·72, 95% CI: 0·53-0·90).

Interpretation: In a rural tropical setting, CAP induced a distinct metabolomic state compared to non-CAP presentations of infection that may reflect the activation of select host immune responses.

Funding: This project was funded by US NIH awards T32HL007287, F32HL168809, K08HL157562, U01AI115520, R01AI137111, R01GM114029, R21AI173435, the Wellcome Trust grants 090219/Z/09/Z and 101103/Z/13/Z, and Firland Foundation award 20220012.

Declaration of Interest: Authors of this manuscript have no conflicts of interest to report.

Ethical Approval: This study was approved by the Mahidol University Faculty of Tropical Medicine Ethics Committee (MUTM 2012-024-01, MUTM 2018-046-01, and MUTM 2024-022-01), the Sunpasitthiprasong Hospital Ethics Committee (039/2556), the Udon Thani Hospital Ethics Committee, the University of Washington Institutional Review Board (42988), and the University of Oxford Tropical Research Ethics Committee (OXTREC172-12). Informed consent was obtained from all study participants or their representatives.

Keywords: community-acquired pneumonia, immune response, low- and middle-income countries (LMICs), predictive modeling

Suggested Citation

Coston, Taylor D. and Xia, Lu and Wright, Shelton W. and Hantrakun, Viriya and Chamnan, Parinya and Wongsuvan, Gumphol and Phunpang, Rungnapa and Dulsuk, Adul and Thiansukhon, Ekkachai and Shojaie, Ali and Chantratita, Narisara and Limmathurotsakul, Direk and Gharib, Sina A. and West, T. Eoin, Pneumonia-Specific Plasma Metabolite Profiles Among Patients Hospitalized with Infection in Southeast Asia. Available at SSRN: https://ssrn.com/abstract=4851914 or http://dx.doi.org/10.2139/ssrn.4851914

Taylor D. Coston (Contact Author)

University of Washington ( email )

Lu Xia

Michigan State University ( email )

Agriculture Hall
East Lansing, MI 48824-1122
United States

Shelton W. Wright

University of Washington ( email )

Seattle, WA 98195
United States

Viriya Hantrakun

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit ( email )

Parinya Chamnan

Sunpasitthiprasong Hospital ( email )

Gumphol Wongsuvan

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit ( email )

Rungnapa Phunpang

Mahidol University ( email )

Adul Dulsuk

Mahidol University ( email )

Ekkachai Thiansukhon

Sunpasitthiprasong Hospital ( email )

Ali Shojaie

University of Washington

Seattle, WA 98195
United States

Narisara Chantratita

Mahidol University ( email )

Direk Limmathurotsakul

Mahidol University - Mahidol-Oxford Tropical Medicine Research Unit ( email )

Thailand

Sina A. Gharib

University of Washington ( email )

T. Eoin West

University of Washington

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