{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:43:07Z","timestamp":1792363387152,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012626","name":"Japan Allergy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012626","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The plasma proteome was evaluated using an aptamer\u2010based affinity proteomics platform (SOMAscan\u00ae), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical\/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune\/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under\u2010explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This investigational study evaluating the plasma proteome in clinically\u2010phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.12091","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T14:21:16Z","timestamp":1640010076000},"source":"Crossref","is-referenced-by-count":18,"title":["Large\u2010scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-6793","authenticated-orcid":false,"given":"Masaru","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Cole","sequence":"additional","affiliation":[{"name":"GLAZgo Discovery Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Konno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironi","family":"Makita","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"},{"name":"Hokkaido Medical Research Institute for Respiratory Diseases  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University  Sapporo Japan"},{"name":"Hokkaido Medical Research Institute for Respiratory Diseases  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-7828","authenticated-orcid":false,"given":"Rose A.","family":"Maciewicz","sequence":"additional","affiliation":[{"name":"GLAZgo Discovery Centre University of Glasgow  Glasgow UK"},{"name":"Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development Biotech Unit AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Global Strategy for the Diagnosis, Management, and Prevention of COPD, 2021 Report","author":"Global Initiative for Chronic Obstructive Lung Disease (GOLD)"},{"key":"e_1_2_8_3_1","unstructured":"Global Initiative for Asthma (GINA).Global strategy for asthma management and prevention.https:\/\/www.ginasthma.org. 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