{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:24:42Z","timestamp":1793424282290,"version":"4.5.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":1737,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council\/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts. The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus. The Haemophilus-predominant subgroup had elevated sputum IL-1\u03b2 and TNF\u03b1 (tumor necrosis factor \u03b1) and was relatively stable over time. The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic. Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations. This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive. Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time. Network analysis revealed distinct host\u2013microbiome interaction patterns among neutrophilic Haemophilus-predominant, neutrophilic balanced microbiome, and eosinophilic subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies. Neutrophilic and eosinophilic COPD are interchangeable in some patients. Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202009-3448oc","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T18:50:37Z","timestamp":1608231037000},"page":"1488-1502","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":239,"title":["Inflammatory Endotype\u2013associated Airway Microbiome in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations: A Multicohort Longitudinal Analysis"],"prefix":"10.1093","volume":"203","author":[{"given":"Zhang","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Locantore","sequence":"additional","affiliation":[{"name":"Medical Innovation, Value Evidence and Outcomes, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koirobi","family":"Haldar","sequence":"additional","affiliation":[{"name":"Human Genetics, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadali Yavari","family":"Ramsheh","sequence":"additional","affiliation":[{"name":"Human Genetics, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusta S.","family":"Beech","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute of Statistics and Big Data, Renmin University of China, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Tal-Singer","sequence":"additional","affiliation":[{"name":"Chronic Obstructive Pulmonary Disease Foundation, Research Department, Washington, District of Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Barer","sequence":"additional","affiliation":[{"name":"Human Genetics, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-2478","authenticated-orcid":false,"given":"Mona","family":"Bafadhel","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin C.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadwiga A.","family":"Wedzicha","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom M. 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