{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:42:12Z","timestamp":1791405732518,"version":"4.3.3"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO\u2010high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To explore airway pathology in T2 biomarker\u2010high and \u2010low severe asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      T2 biomarker\u2010high severe asthma (T2\u2010high,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a017) was compared with biomarker\u2010intermediate (T2\u2010intermediate,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a021) and biomarker\u2010low (T2\u2010low,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a020) severe asthma and healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a028). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD\n                      <jats:sub>2<\/jats:sub>\n                      and LTE\n                      <jats:sub>4<\/jats:sub>\n                      measurements.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodelling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared with health, but similar across asthma subgroups. Submucosal glands were increased in T2\u2010intermediate and T2\u2010low asthma. In spite of similar tissue cellular inflammation, sputum IL\u20104, IL\u20105 and CCL26 were increased in T2\u2010high versus T2\u2010low asthma, and several further T2\u2010associated cytokines, PGD\n                      <jats:sub>2<\/jats:sub>\n                      and LTE\n                      <jats:sub>4<\/jats:sub>\n                      , were increased in T2\u2010high and T2\u2010intermediate asthma compared with healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker\u2010high and T2\u2010low severe asthma, but inflammatory and structural cell activation is present, with sputum T2\u2010associated cytokines highest in T2 biomarker\u2010high patients. Airway remodelling persists and may be important for residual disease expression beyond eosinophilic exacerbations.<\/jats:p>\n                    <jats:p>\n                      Registered at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clincialtrials.gov\">ClincialTrials.gov<\/jats:ext-link>\n                      : NCT02883530.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.15376","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T05:08:25Z","timestamp":1652764105000},"page":"2974-2986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker\u2010high and \u2010low severe asthma"],"prefix":"10.1111","volume":"77","author":[{"given":"Latifa","family":"Khalfaoui","sequence":"first","affiliation":[{"name":"Department of Respiratory Sciences, Leicester Respiratory NIHR BRC, Glenfield Hospital University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona A.","family":"Symon","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, Leicester Respiratory NIHR BRC, Glenfield Hospital University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-6886","authenticated-orcid":false,"given":"Simon","family":"Couillard","sequence":"additional","affiliation":[{"name":"NIHR Oxford Respiratory BRC, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Hargadon","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, Leicester Respiratory NIHR BRC, Glenfield Hospital University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Gartnavel General Hospital, Glasgow, and Institute of Infection, Immunity and Inflammation University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Bicknell","sequence":"additional","affiliation":[{"name":"Gartnavel General Hospital, Glasgow, and Institute of Infection, Immunity and Inflammation University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-8778","authenticated-orcid":false,"given":"Adel H.","family":"Mansur","sequence":"additional","affiliation":[{"name":"University of Birmingham and Heartlands Hospital University Hospitals Birmingham NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Shrimanker","sequence":"additional","affiliation":[{"name":"NIHR Oxford Respiratory BRC, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-2373","authenticated-orcid":false,"given":"Timothy\u00a0S. C.","family":"Hinks","sequence":"additional","affiliation":[{"name":"NIHR Oxford Respiratory BRC, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-5973","authenticated-orcid":false,"given":"Ian D.","family":"Pavord","sequence":"additional","affiliation":[{"name":"NIHR Oxford Respiratory BRC, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4524-1663","authenticated-orcid":false,"given":"Stephen J.","family":"Fowler","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Brown","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson\u2010 Centre for Experimental Medicine Queen's University Belfast School of Medicine Dentistry and Biomedical Sciences  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorcan P.","family":"McGarvey","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson\u2010 Centre for Experimental Medicine Queen's University Belfast School of Medicine Dentistry and Biomedical Sciences  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-5564","authenticated-orcid":false,"given":"Liam G.","family":"Heaney","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson\u2010 Centre for Experimental Medicine Queen's University Belfast School of Medicine Dentistry and Biomedical Sciences  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary D.","family":"Austin","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Howarth","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, NIHR Southampton Biomedical Research Centre University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Arron","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Choy","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8403-0319","authenticated-orcid":false,"given":"Peter","family":"Bradding","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, Leicester Respiratory NIHR BRC, Glenfield Hospital University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00116203"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200409-1181PP"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.6.ats9-00"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.073429"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1640OC"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30397-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-215168"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200903-0392OC"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002568"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab3142"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.03.027"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17974"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304048"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808991"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.014"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.08.031"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.12.982"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01129-2016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80911"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02135-2016"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12125"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13731"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201806-1182OC"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.10.059"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0587OC"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-203618"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.98.12040811"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202104-1040LE"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60988-X"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01874-2019"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.13f06.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9812110"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/145.3.669"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(06)80008-4"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201611-2234OC"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804092"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403290"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30031-5"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201707-1323OC"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.2.4600"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.10.037"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00004-7"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200209-1030OC"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1978.tb01735.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1922.00110120002001"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.57.8.677"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95693"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.2.2004039"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(03)00241-9"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.13.1.27"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100441"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.10.004"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145259"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12675"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202102-0355OC"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.10.5.8179909"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9801007"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02122.x"},{"key":"e_1_2_9_60_1","first-page":"4612","article-title":"Late Breaking Abstract \u2010 Masitinib in severe asthma: Results from a randomized, phase 3 trial","volume":"56","author":"Davidescu L","year":"2020","journal-title":"Eur Respir J"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012705"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.062141"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/142.4.863"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.14b07.x"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00117013"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00023-0"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600606"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168680"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.044"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.15376","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.15376","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.15376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T21:17:11Z","timestamp":1692652631000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.15376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/all.15376"],"URL":"https:\/\/doi.org\/10.1111\/all.15376","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]},"assertion":[{"value":"2021-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}