{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:00:00Z","timestamp":1792184400025,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.<\/jats:p>","DOI":"10.3390\/cells13060475","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:33:06Z","timestamp":1709811186000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Exploring the Potential Role of Metabolomics in COPD: A Concise Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-9902","authenticated-orcid":false,"given":"Claudio","family":"Tirelli","sequence":"first","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Mira","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Alessandro","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"De Filippi","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"De Grassi","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Italia","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Maggioni","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8429-2154","authenticated-orcid":false,"given":"Gabriele","family":"Guido","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mondoni","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio Walter","family":"Canonica","sequence":"additional","affiliation":[{"name":"Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Clinical and Research Center, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Centanni","sequence":"additional","affiliation":[{"name":"Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S2213-2600(21)00511-7","article-title":"Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: A systematic review and modelling analysis","volume":"10","author":"Adeloye","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Piloni, D., Ottaviani, S., Saderi, L., Corda, L., Baderna, P., Barzon, V., Balderacchi, A.M., Seebacher, C., Balbi, B., and Albicini, F. (2023). Comparison among populations with severe and intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease. Minerva Medica.","DOI":"10.23736\/S0026-4806.22.08266-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.2147\/COPD.S429104","article-title":"Prediction of Hospitalization and Mortality in Patients with Chronic Obstructive Pulmonary Disease with the New Global Initiative for Chronic Obstructive Lung Disease 2023 Group Classification: A Prospective Cohort and a Retrospective Analysis","volume":"18","author":"Cheng","year":"2023","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/nbm.935","article-title":"NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition","volume":"18","author":"Bollard","year":"2005","journal-title":"NMR Biomed."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tirelli, C., Pesenti, C., Miozzo, M., Mondoni, M., Fontana, L., and Centanni, S. (2022). The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis: A State-of-the-Art Review. Diagnostics, 12.","DOI":"10.3390\/diagnostics12123107"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1016\/j.radcr.2020.08.012","article-title":"CT-guided biopsy in the differential diagnosis of Sjogren syndrome associated cystic lung disease: A case of lung nodular AL-k amyloidosis","volume":"15","author":"Tirelli","year":"2020","journal-title":"Radiol. Case Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/456443c","article-title":"Marker metabolites can be therapeutic targets as well","volume":"456","author":"Arakaki","year":"2008","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1701930","DOI":"10.1183\/13993003.01930-2017","article-title":"Integration of multi-omics datasets enables molecular classification of COPD","volume":"51","author":"Li","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.2174\/0929867325666181008122749","article-title":"Metabolomics of Exhaled Breath Condensate by Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: A Methodological Approach","volume":"27","author":"Maniscalco","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1038\/nprot.2007.376","article-title":"Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts","volume":"2","author":"Beckonert","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/bs.acc.2018.10.002","article-title":"Clinical metabolomics of exhaled breath condensate in chronic respiratory diseases","volume":"88","author":"Maniscalco","year":"2019","journal-title":"Adv. Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.2174\/1568026616666151223113540","article-title":"Electronic Nose and Exhaled Breath NMR-based Metabolomics Applications in Airways Disease","volume":"16","author":"Santini","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12931-017-0631-9","article-title":"Using omics approaches to understand pulmonary diseases","volume":"18","author":"Kan","year":"2017","journal-title":"Respir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1801107","DOI":"10.1183\/13993003.01107-2018","article-title":"Nuclear magnetic resonance-based metabolomics in respiratory medicine","volume":"52","author":"Paris","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1183\/09031936.05.00029705","article-title":"ATS\/ERS Task Force on Exhaled Breath Condensate. Exhaled breath condensate: Methodological recommendations and unresolved questions","volume":"26","author":"Horvath","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.talanta.2010.07.015","article-title":"Fast quantification of the exhaled breath condensate of oxidative stress 8-iso-prostaglandin F2\u03b1 using on-line solid-phase extraction coupled with liquid chromatography\/electrospray ionization mass spectrometry","volume":"82","author":"Wang","year":"2010","journal-title":"Talanta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"044001","DOI":"10.1088\/1752-7163\/ac15ea","article-title":"Multi-omics study on biomarker and pathway discovery of chronic obstructive pulmonary disease","volume":"15","author":"Tang","year":"2021","journal-title":"J. Breath Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"The Standard Metabolic Reporting Structures Working Group, Lindon, J.C., Nicholson, J.K., Holmes, E., Keun, H.C., Craig, A., Pearce, J.T.M., Bruce, S.J., Hardy, N., and Sansone, S.-A. (2005). Summary recommendations for standardization and reporting of metabolic analyses. Nat. Biotechnol., 23, 833\u2013838.","DOI":"10.1038\/nbt0705-833"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Keun, H.C. (2018). NMR-Based Metabolomics, RSC Publishing.","DOI":"10.1039\/9781782627937"},{"key":"ref_20","first-page":"233","article-title":"Metabolic profiling","volume":"Volume II","author":"Holzgrabe","year":"2010","journal-title":"NMR Spectroscopy in Pharmaceutical Analysis"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Scarlata, S., Finamore, P., Meszaros, M., Dragonieri, S., and Bikov, A. (2020). The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease. Biosensors, 10.","DOI":"10.3390\/bios10110171"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000340044","article-title":"The electronic nose in respiratory medicine","volume":"85","author":"Montuschi","year":"2013","journal-title":"Respiration"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1586\/14737159.2015.1043895","article-title":"Exhaled breath analysis by electronic nose in respiratory diseases","volume":"15","author":"Scarlata","year":"2015","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2217\/bmm-2017-0068","article-title":"Metabolomics of exhaled breath condensate: A means for phenotyping respiratory diseases?","volume":"11","author":"Maniscalco","year":"2017","journal-title":"Biomarkers Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/4551054a","article-title":"Systems biology: Metabonomics","volume":"455","author":"Nicholson","year":"2008","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.iac.2018.06.002","article-title":"Exhaled Breath Condensate","volume":"38","author":"Davis","year":"2018","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.rmed.2007.10.014","article-title":"Long-term repeatability of exhaled breath condensate pH in asthma","volume":"102","author":"Accordino","year":"2008","journal-title":"Respir. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Psychogios, N., Hau, D.D., Peng, J., Guo, A.C., Mandal, R., Bouatra, S., Sinelnikov, I., Krishnamurthy, R., Eisner, R., and Gautam, B. (2011). The human serum metabolome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016957"},{"key":"ref_29","first-page":"659","article-title":"Metabolomic Profiling Differences among Asthma, COPD, and Healthy Subjects: A LC-MS-based Metabolomic Analysis","volume":"32","author":"Liang","year":"2019","journal-title":"Biomed. Environ. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bbrc.2011.09.006","article-title":"Pilot analysis of the plasma metabolite profiles associated with emphysematous Chronic Obstructive Pulmonary Disease phenotype","volume":"413","author":"Paige","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1164\/rccm.201110-1792OC","article-title":"Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease","volume":"185","author":"Celli","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Halper-Stromberg, E., Gillenwater, L., Cruickshank-Quinn, C., O\u2019neal, W.K., Reisdorph, N., Petrache, I., Zhuang, Y., Labaki, W.W., Curtis, J.L., and Wells, J. (2019). Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma. Metabolites, 9.","DOI":"10.3390\/metabo9080157"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"433","DOI":"10.23736\/S0026-4806.22.08245-3","article-title":"Serum Aspergillus-specific IgE, IgG and IgG4 immunoglobulins assessment in the work-up of invasive pulmonary aspergillosis: A prospective cohort study","volume":"114","author":"Tirelli","year":"2023","journal-title":"Minerva Medica"},{"key":"ref_34","first-page":"148","article-title":"Eosinophilic cationic protein (ECP) in the clinical work-up of chronic cough","volume":"114","author":"Piloni","year":"2023","journal-title":"Minerva Medica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1183\/13993003.01080-2015","article-title":"Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD","volume":"47","author":"Balgoma","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1378\/chest.14-2868","article-title":"Acute Exacerbations of COPD Are Associated with Increased Expression of Heparan Sulfate and Chondroitin Sulfate in BAL","volume":"149","author":"Papakonstantinou","year":"2016","journal-title":"Chest"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, L., and Tang, Y. (2013). Metabonomic profiling of serum and urine by (1)H NMR-based spectroscopy discriminates patients with chronic obstructive pulmonary disease and healthy individuals. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065675"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.2147\/COPD.S298678","article-title":"Eicosanoids and Eosinophilic Inflammation of Airways in Stable COPD","volume":"16","author":"Kania","year":"2021","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.chest.2021.10.049","article-title":"Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD","volume":"161","author":"Esther","year":"2022","journal-title":"Chest"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Godbole, S., and Bowler, R.P. (2022). Metabolome Features of COPD: A Scoping Review. Metabolites, 12.","DOI":"10.3390\/metabo12070621"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.1038\/s41467-020-19701-0","article-title":"Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease","volume":"11","author":"Bowerman","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chen, Q., Deeb, R.S., Ma, Y., Staudt, M.R., Crystal, R.G., and Gross, S.S. (2015). Serum metabolite biomarkers discriminate healthy smokers from COPD smokers. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143937"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11087","DOI":"10.1038\/s41598-017-11339-1","article-title":"Lipidomes of lung cancer and tumour-free lung tissues reveal distinct molecular signatures for cancer differentiation, age, inflammation, and pulmonary emphysema","volume":"7","author":"Eggers","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1136\/thoraxjnl-2020-215892","article-title":"Ceramide and sphingosine-1 phosphate in COPD lungs","volume":"76","author":"Berdyshev","year":"2021","journal-title":"Thorax"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.amjmed.2012.06.024","article-title":"Inflammation in COPD: Implications for management","volume":"125","author":"Sethi","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s12603-014-0459-7","article-title":"Exercise-induced lowering of chemerin is associated with reduced cardiometabolic risk and glucose-stimulated insulin secretion in older adults","volume":"18","author":"Malin","year":"2014","journal-title":"J. Nutr. Health Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1530\/JOE-18-0174","article-title":"Chemerin: A multifaceted adipokine involved in metabolic disorders","volume":"238","author":"Helfer","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1210\/jc.2010-0042","article-title":"Chemerin, a novel adipokine in the regulation of angiogenesis","volume":"95","author":"Bozaoglu","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.2337\/db16-0331","article-title":"Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation","volume":"65","author":"Ghosh","year":"2016","journal-title":"Diabetes"},{"key":"ref_50","first-page":"431","article-title":"The role of chemerin in the pathogenesis of COPD","volume":"37","author":"Fu","year":"2014","journal-title":"J. Zunyi Med. Univ."},{"key":"ref_51","first-page":"676","article-title":"Plasma level of chemerin in COPD patients and the relationship between chemerin and lipid metabolism","volume":"41","author":"Li","year":"2016","journal-title":"J. Cent. South Univ."},{"key":"ref_52","first-page":"569","article-title":"Effect of salmeterol propionate fluticasone combined with lip shrinkage respiration on chemerin level and lipid metabolism in patients with chronic obstructive pulmonary disease","volume":"10","author":"Fang","year":"2017","journal-title":"Chin. J. Lung Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Oliveira, G.P., de Abreu, M.G., Pelosi, P., and Rocco, P.R. (2016). Exogenous Glutamine in Respiratory Diseases: Myth or Reality?. Nutrients, 8.","DOI":"10.3390\/nu8020076"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1039\/c2mb25194a","article-title":"Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD","volume":"8","author":"Ubhi","year":"2012","journal-title":"Mol. Biosyst."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1164\/rccm.201410-1771OC","article-title":"Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes","volume":"191","author":"Bowler","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1089\/nsm.2020.0009","article-title":"Plasma Metabolomic Signatures of Chronic Obstructive Pulmonary Disease and the Impact of Genetic Variants on Phenotype-Driven Modules","volume":"3","author":"Lucas","year":"2020","journal-title":"Netw. Syst. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2147\/COPD.S229505","article-title":"Plasma Metabolomics and Lipidomics Reveal Perturbed Metabolites in Different Disease Stages of Chronic Obstructive Pulmonary Disease","volume":"15","author":"Zhou","year":"2020","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1701825","DOI":"10.1183\/13993003.01825-2017","article-title":"Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: A pilot study","volume":"51","author":"Maniscalco","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s11306-013-0572-3","article-title":"Phenotyping COPD by 1H NMR metabolomics of exhaled breath condensate","volume":"10","author":"Bertini","year":"2014","journal-title":"Metabolomics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1021\/pr301171p","article-title":"Separating smoking-related diseases using NMR-based metabolomics of exhaled breath condensate","volume":"12","author":"Paris","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.freeradbiomed.2018.11.023","article-title":"Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis","volume":"131","author":"Bodas","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12012-018-9493-8","article-title":"Endothelial Cells: From Dysfunction Mechanism to Pharmacological Effect in Cardiovascular Disease","volume":"19","author":"Haybar","year":"2019","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1189\/jlb.4VMR0316-103R","article-title":"Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation","volume":"100","author":"Shaikh","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1183\/09031936.00112411","article-title":"Metabolic profiling detects biomarkers of protein degradation in COPD patients","volume":"40","author":"Ubhi","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11306-015-0920-6","article-title":"Metabolomics of chronic obstructive pulmonary disease and obstructive sleep apnea syndrome: A comment","volume":"12","author":"Maniscalco","year":"2016","journal-title":"Metabolomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1038715","DOI":"10.3389\/fimmu.2022.1038715","article-title":"Lung cancer patients with chronic obstructive pulmonary disease benefit from anti-PD-1\/PD-L1 therapy","volume":"13","author":"Lin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"22402","DOI":"10.1038\/s41598-022-26650-9","article-title":"Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer","volume":"12","author":"Polverino","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.chembiol.2023.06.016","article-title":"Hydroxyproline metabolism enhances IFN-\u03b3-induced PD-L1 expression and inhibits autophagic flux","volume":"30","author":"Spangenberg","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107011","DOI":"10.1016\/j.rmed.2022.107011","article-title":"Early chronic obstructive pulmonary disease: Associations of two spirometry criteria with clinical features","volume":"204","author":"Mochizuki","year":"2022","journal-title":"Respir. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"761767","DOI":"10.3389\/fmed.2021.761767","article-title":"Telomere length but not mitochondrial DNA copy number is altered in both young and old COPD","volume":"8","author":"Mendoza","year":"2021","journal-title":"Front. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1093\/ageing\/afz083","article-title":"New horizons in arginine metabolism, ageing and chronic disease states","volume":"48","author":"Mangoni","year":"2019","journal-title":"Age Ageing"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.vh.2018.02.002","article-title":"Dehydroepiandrosterone research: Past, current, and future","volume":"108","author":"Klinge","year":"2018","journal-title":"Vitam. Horm."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"668","DOI":"10.2174\/1389203718666170529105026","article-title":"Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia","volume":"19","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1602322","DOI":"10.1183\/13993003.02322-2016","article-title":"Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD","volume":"49","author":"Naz","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"00180","DOI":"10.1183\/23120541.00180-2023","article-title":"Update on metabolomic findings in COPD patients","volume":"9","author":"Gea","year":"2023","journal-title":"ERJ Open Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/6\/475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:10:37Z","timestamp":1760105437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/6\/475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["cells13060475"],"URL":"https:\/\/doi.org\/10.3390\/cells13060475","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}