{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:21:05Z","timestamp":1776914465410,"version":"3.51.2"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The ATLANTIS study included 773 asthma patients (mean age 44\u2009years, 58% female, 76% never\u2010smoker, GINA 1\u20135). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome\u2010wide gene expression profiling from nasal brushes. Clusters were generated using the Self\u2010Organizing Map\u2013Ward's method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four distinct clusters were identified: A (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200962; 8%) characterized by the most frequent exacerbations, lower post\u2010bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma\u2010related genes. B (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009206; 27%) consisting of atopic patients with early\u2010onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma\u2010related genes in the nasal epithelium. C (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009277; 36%), predominantly male former smokers, with well\u2010controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009228; 29%), with normal lung function and low blood and sputum eosinophils.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Four distinct clusters were identified, where the presence of SAD was associated with high type\u20102 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70127","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:41:04Z","timestamp":1762789264000},"page":"185-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cluster Analysis to Identify Distinct Asthma Phenotypes in the\n                    <scp>ATLANTIS<\/scp>\n                    Cohort"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0220-8985","authenticated-orcid":false,"given":"Pauline J. M.","family":"Kuks","sequence":"first","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6435-4545","authenticated-orcid":false,"given":"Tatiana","family":"Karp","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-9673","authenticated-orcid":false,"given":"Jorine E.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Kraft","sequence":"additional","affiliation":[{"name":"Samuel Bronfman Department of Medicine Icahn School of Medicine, Mount Sinai Medical Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-7870","authenticated-orcid":false,"given":"Salman","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo M.","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Morphology, Surgery and Experimental Medicine, Section of Respiratory Medicine University of Ferrara  Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Begh\u00e9","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-1401","authenticated-orcid":false,"given":"Klaus F.","family":"Rabe","sequence":"additional","affiliation":[{"name":"Department of Medicine Christian Albrechts University Kiel  Kiel Germany"},{"name":"LungenClinic  Grosshansdorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6924-4500","authenticated-orcid":false,"given":"Alberto","family":"Papi","sequence":"additional","affiliation":[{"name":"Section of Respiratory Medicine, Department of Translational Medicine University of Ferrara  Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[{"name":"The Institute for Lung Health, NIHR Leicester Biomedical Research Centre University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Medicine and Allergy University of Manchester, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingnan","family":"Li","sequence":"additional","affiliation":[{"name":"Samuel Bronfman Department of Medicine Icahn School of Medicine, Mount Sinai Medical Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janwillem W. H.","family":"Kocks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"General Practitioners Research Institute  Groningen the Netherlands"},{"name":"Observational and Pragmatic Research Institute  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrica","family":"Scaffidi\u2010Argentina","sequence":"additional","affiliation":[{"name":"Global Medical Affairs Chiesi Farmaceutici S.p.A.  Parma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huib A. M.","family":"Kerstjens","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-8932","authenticated-orcid":false,"given":"Irene H.","family":"Heijink","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-8061","authenticated-orcid":false,"given":"Simon D.","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk\u2010Jan","family":"Slebos","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten","family":"van den Berge","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, University Medical Center Groningen University of Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"World Health Organization (WHO) \u201cAsthma [Internet] \u201d(2024) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/asthma."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-32259-4_7"},{"issue":"1","key":"e_1_2_8_4_1","first-page":"1","article-title":"The New Era of Add\u2010On Asthma Treatments: Where Do We Stand?","volume":"18","author":"Calhoun W. J.","year":"2022","journal-title":"Allergy, Asthma and Clinical Immunology"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41030-016-0017-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0482-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200906-0896OC"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102987"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200711-1754OC"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30049-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112617"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.01.047"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72551-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50963-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00536-1"},{"key":"e_1_2_8_16_1","unstructured":"GINA \u201cGlobal Initiative for Asthma Management and Prevention \u201d Labels and Labelling (2012):56\u201361."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2023-221230"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2013.03.009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03820.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2019.01.016"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.052241"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01962-2017"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1586\/17476348.2015.1000311"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01029.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00616\u20102024"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.011"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.70127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T14:50:56Z","timestamp":1771167056000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.70127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/all.70127"],"URL":"https:\/\/doi.org\/10.1111\/all.70127","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}