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Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD

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Abstract

Introduction

Asthma-chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease without any clear diagnostic or therapeutic guidelines. The pathophysiology of the disease, its characteristic features, and existence as a unique disease entity remains unclear. Individuals with ACO have a faster lung function decline, more frequent exacerbations, and worse quality of life than those with COPD or asthma alone.

Objectives

The present study aims to determine whether ACO has a distinct metabolic profile in comparison to asthma and COPD.

Methods

Two different groups of patients were recruited as discovery (D) and validation (V) cohorts. Serum samples obtained from moderate and severe asthma patients diagnosed as per GINA guidelines [n = 34(D); n = 32(V)], moderate and severe COPD cases identified by GOLD guidelines [n = 30(D); 32(V)], ACO patients diagnosed by joint GOLD and GINA guidelines [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using nuclear magnetic resonance (NMR) spectrometry.

Results

Multivariate and univariate analysis indicated that 12 metabolites [lipid, isoleucine, N-acetylglycoproteins (NAG), valine, glutamate, citric acid, glucose, l-leucine, lysine, asparagine, phenylalanine and histidine] were dysregulated in ACO patients when compared with both asthma and COPD. These metabolites were further validated in a fresh cohort of patients, which again exhibited a similar expression pattern.

Conclusions

Our findings suggest that ACO has an enhanced energy and metabolic burden associated with it as compared to asthma and COPD. It is anticipated that our results will stimulate researchers to further explore ACO and unravel the pathophysiological complexities associated with the disease.

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Acknowledgements

Financial support by Government of India, Ministry of Human Resource Development (Grant No: F. NO. 4-23/2014-TS.I, Dt. 14-03-2014) and Department of Higher Education (SSLS project) and Department of Science and Technology (DST), Govt. of West Bengal (Grant No: 867(Sanc.)/ST/P/S&T/9G-17/2015, Dt. 15-01-2016) are acknowledged.

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NG, RB, SRC, PB and KC conceived and designed the study. NG, PC, DS, SS and MJ conducted experiments. NG, PC, ES and KC analyzed the data. NG, KC, SRC and PB wrote the paper. All authors critically revised, read, and approved the final version of manuscript.

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Correspondence to Koel Chaudhury.

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All procedures performed in the study involving human participants were done in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Ghosh, N., Choudhury, P., Subramani, E. et al. Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD. Metabolomics 15, 87 (2019). https://doi.org/10.1007/s11306-019-1552-z

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