PMID- 32448302 OWN - NLM STAT- MEDLINE DCOM- 20210315 LR - 20210315 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 21 IP - 1 DP - 2020 May 24 TI - Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO). PG - 126 LID - 10.1186/s12931-020-01390-4 [doi] LID - 126 AB - BACKGROUND: Asthma-COPD overlap (ACO) refers to a group of poorly studied and characterised patients reporting with disease presentations of both asthma and COPD, thereby making both diagnosis and treatment challenging for the clinicians. They exhibit a higher burden in terms of both mortality and morbidity in comparison to patients with only asthma or COPD. The pathophysiology of the disease and its existence as a unique disease entity remains unclear. The present study aims to determine whether ACO has a distinct metabolic and immunological mediator profile in comparison to asthma and COPD. METHODS: Global metabolomic profiling using two different groups of patients [discovery (D) and validation (V)] were conducted. Serum samples obtained from moderate and severe asthma [n = 34(D); n = 32(V)], moderate and severe COPD [n = 30(D); 32(V)], ACO patients [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using gas chromatography mass spectrometry (GC-MS). Multiplexed analysis of 25 immunological markers (IFN-gamma (interferon gamma), TNF-alpha (tumor necrosis factor alpha), IL-12p70 (interleukin 12p70), IL-2, IL-4, IL-5, IL-13, IL-10, IL-1alpha, IL-1beta, TGF-beta (transforming growth factor), IL-6, IL-17E, IL-21, IL-23, eotaxin, GM-CSF (granulocyte macrophage-colony stimulating factor), IFN-alpha (interferon alpha), IL-18, NGAL (neutrophil gelatinase-associated lipocalin), periostin, TSLP (thymic stromal lymphopoietin), MCP-1 (monocyte chemoattractant protein- 1), YKL-40 (chitinase 3 like 1) and IL-8) was also performed in the discovery cohort. RESULTS: Eleven metabolites [serine, threonine, ethanolamine, glucose, cholesterol, 2-palmitoylglycerol, stearic acid, lactic acid, linoleic acid, D-mannose and succinic acid] were found to be significantly altered in ACO as compared with asthma and COPD. The levels and expression trends were successfully validated in a fresh cohort of subjects. Thirteen immunological mediators including TNFalpha, IL-1beta, IL-17E, GM-CSF, IL-18, NGAL, IL-5, IL-10, MCP-1, YKL-40, IFN-gamma, IL-6 and TGF-beta showed distinct expression patterns in ACO. These markers and metabolites exhibited significant correlation with each other and also with lung function parameters. CONCLUSIONS: The energy metabolites, cholesterol and fatty acids correlated significantly with the immunological mediators, suggesting existence of a possible link between the inflammatory status of these patients and impaired metabolism. The present findings could be possibly extended to better define the ACO diagnostic criteria, management and tailoring therapies exclusively for the disease. FAU - Ghosh, Nilanjana AU - Ghosh N AD - School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. FAU - Choudhury, Priyanka AU - Choudhury P AD - School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. FAU - Kaushik, Sandeep Rai AU - Kaushik SR AD - Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. FAU - Arya, Rakesh AU - Arya R AD - Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. FAU - Nanda, Ranjan AU - Nanda R AD - Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. FAU - Bhattacharyya, Parthasarathi AU - Bhattacharyya P AD - Institute of Pulmocare and Research, Kolkata, India. FAU - Roychowdhury, Sushmita AU - Roychowdhury S AD - Apollo Gleneagles Hospital, Kolkata, India. FAU - Banerjee, Rintu AU - Banerjee R AD - Department of Agricultural and Food Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India. FAU - Chaudhury, Koel AU - Chaudhury K AUID- ORCID: 0000-0002-9390-1179 AD - School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. koel@smst.iitkgp.ac.in. LA - eng GR - Grant No: F. NO. 4-23/2014-TS.I, Dt. 14-03-2014/Ministry of Human Resource Development/ GR - Grant No: 867(Sanc.)/ST/P/S&T/9G-17/2015, Dt. 15-01-2016/Department of Science and Technology, Government of West Bengal/ PT - Journal Article DEP - 20200524 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Inflammation Mediators) SB - IM MH - Adult MH - Asthma/genetics/*metabolism MH - Cohort Studies MH - DNA Fingerprinting/*methods MH - Female MH - Gene Expression Profiling/*methods MH - Humans MH - Inflammation Mediators/*metabolism MH - Male MH - Metabolomics/*methods MH - Middle Aged MH - Pilot Projects MH - Pulmonary Disease, Chronic Obstructive/genetics/*metabolism MH - Random Allocation PMC - PMC7245917 OTO - NOTNLM OT - Asthma COPD overlap (ACO) OT - Inflammatory mediators OT - Mass spectrometry OT - Metabolomics EDAT- 2020/05/26 06:00 MHDA- 2021/03/16 06:00 PMCR- 2020/05/24 CRDT- 2020/05/26 06:00 PHST- 2020/02/22 00:00 [received] PHST- 2020/05/10 00:00 [accepted] PHST- 2020/05/26 06:00 [entrez] PHST- 2020/05/26 06:00 [pubmed] PHST- 2021/03/16 06:00 [medline] PHST- 2020/05/24 00:00 [pmc-release] AID - 10.1186/s12931-020-01390-4 [pii] AID - 1390 [pii] AID - 10.1186/s12931-020-01390-4 [doi] PST - epublish SO - Respir Res. 2020 May 24;21(1):126. doi: 10.1186/s12931-020-01390-4.