Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease

Abstract Asthma—chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacer...

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Main Authors: Nilanjana Ghosh, Priyanka Choudhury, Mamata Joshi, Parthasarathi Bhattacharyya, Sushmita Roychowdhury, Rintu Banerjee, Koel Chaudhury
Format: Article
Language:English
Published: Nature Portfolio 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-96128-7
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author Nilanjana Ghosh
Priyanka Choudhury
Mamata Joshi
Parthasarathi Bhattacharyya
Sushmita Roychowdhury
Rintu Banerjee
Koel Chaudhury
author_facet Nilanjana Ghosh
Priyanka Choudhury
Mamata Joshi
Parthasarathi Bhattacharyya
Sushmita Roychowdhury
Rintu Banerjee
Koel Chaudhury
author_sort Nilanjana Ghosh
collection DOAJ
description Abstract Asthma—chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, increased comorbidities and a faster lung function decline. In absence of clear diagnostic or therapeutic guidelines, ACO presents as a challenge to clinicians. The present study aims to investigate whether ACO patients have a distinct exhaled breath condensate (EBC) metabolic profile in comparison to asthma and COPD. A total of 132 age and BMI matched male smokers were recruited in the exploratory phase which consisted of (i) controls = 33 (ii) asthma = 34 (iii) COPD = 30 and (iv) ACO = 35. Using nuclear magnetic resonance (NMR) metabolomics, 8 metabolites (fatty acid, propionate, isopropanol, lactate, acetone, valine, methanol and formate) were identified to be significantly dysregulated in ACO subjects when compared to both, asthma and COPD. The expression of these dysregulated metabolites were further validated in a fresh patient cohort consisting of (i) asthma = 32 (ii) COPD = 32 and (iii) ACO = 40, which exhibited a similar expression pattern. Multivariate receiver operating characteristic (ROC) curves generated using these metabolites provided a robust ACO classification model. The findings were also integrated with previously identified serum metabolites and inflammatory markers to develop a robust predictive model for differentiation of ACO. Our findings suggest that NMR metabolomics of EBC holds potential as a platform to identify robust, non-invasive biomarkers for differentiating ACO from asthma and COPD.
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spelling doaj.art-e776e262ecd84ba19dd9fb7bfd250b5a2022-12-21T20:36:25ZengNature PortfolioScientific Reports2045-23222021-08-0111111410.1038/s41598-021-96128-7Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the diseaseNilanjana Ghosh0Priyanka Choudhury1Mamata Joshi2Parthasarathi Bhattacharyya3Sushmita Roychowdhury4Rintu Banerjee5Koel Chaudhury6School of Medical Science and Technology, Indian Institute of Technology KharagpurSchool of Medical Science and Technology, Indian Institute of Technology KharagpurNational Facility for High-Field NMR, Tata Institute of Fundamental ResearchInstitute of Pulmocare and ResearchApollo Gleneagles HospitalsDepartment of Agricultural and Food Engineering, Indian Institute of Technology KharagpurSchool of Medical Science and Technology, Indian Institute of Technology KharagpurAbstract Asthma—chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease characterised by persistent airflow limitation, which manifests features of both asthma and COPD. These patients have a worse prognosis, in terms of more frequent and severe exacerbations, more frequent symptoms, worse quality of life, increased comorbidities and a faster lung function decline. In absence of clear diagnostic or therapeutic guidelines, ACO presents as a challenge to clinicians. The present study aims to investigate whether ACO patients have a distinct exhaled breath condensate (EBC) metabolic profile in comparison to asthma and COPD. A total of 132 age and BMI matched male smokers were recruited in the exploratory phase which consisted of (i) controls = 33 (ii) asthma = 34 (iii) COPD = 30 and (iv) ACO = 35. Using nuclear magnetic resonance (NMR) metabolomics, 8 metabolites (fatty acid, propionate, isopropanol, lactate, acetone, valine, methanol and formate) were identified to be significantly dysregulated in ACO subjects when compared to both, asthma and COPD. The expression of these dysregulated metabolites were further validated in a fresh patient cohort consisting of (i) asthma = 32 (ii) COPD = 32 and (iii) ACO = 40, which exhibited a similar expression pattern. Multivariate receiver operating characteristic (ROC) curves generated using these metabolites provided a robust ACO classification model. The findings were also integrated with previously identified serum metabolites and inflammatory markers to develop a robust predictive model for differentiation of ACO. Our findings suggest that NMR metabolomics of EBC holds potential as a platform to identify robust, non-invasive biomarkers for differentiating ACO from asthma and COPD.https://doi.org/10.1038/s41598-021-96128-7
spellingShingle Nilanjana Ghosh
Priyanka Choudhury
Mamata Joshi
Parthasarathi Bhattacharyya
Sushmita Roychowdhury
Rintu Banerjee
Koel Chaudhury
Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
Scientific Reports
title Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
title_full Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
title_fullStr Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
title_full_unstemmed Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
title_short Global metabolome profiling of exhaled breath condensates in male smokers with asthma COPD overlap and prediction of the disease
title_sort global metabolome profiling of exhaled breath condensates in male smokers with asthma copd overlap and prediction of the disease
url https://doi.org/10.1038/s41598-021-96128-7
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