{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:49:49Z","timestamp":1787856589044,"version":"build-2784847793"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01 HL153058"],"award-info":[{"award-number":["R01 HL153058"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["P01 HL164320"],"award-info":[{"award-number":["P01 HL164320"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["1U54HL185005"],"award-info":[{"award-number":["1U54HL185005"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["P30 DK065988"],"award-info":[{"award-number":["P30 DK065988"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL163602"],"award-info":[{"award-number":["R01 HL163602"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["T32 AI007062"],"award-info":[{"award-number":["T32 AI007062"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["T32 HL007106"],"award-info":[{"award-number":["T32 HL007106"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"publisher","award":["UM1TR004406"],"award-info":[{"award-number":["UM1TR004406"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"publisher","award":["K12 TR004416"],"award-info":[{"award-number":["K12 TR004416"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Academy of Allergy"},{"name":"Asthma & Immunology Allergic Respiratory Disease"},{"name":"Asthma & Immunology Foundation Faculty Development"},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CFF R026"],"award-info":[{"award-number":["CFF R026"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BOUCHER22G0"],"award-info":[{"award-number":["BOUCHER22G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ESTHER24R0"],"award-info":[{"award-number":["ESTHER24R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["MURANO25F0"],"award-info":[{"award-number":["MURANO25F0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["KATO22G0"],"award-info":[{"award-number":["KATO22G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Bronchiolar dysfunction is associated with asthma exacerbations and poor symptom control. However, the molecular pathophysiology of asthmatic bronchiolar disease is poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Test the hypothesis that asthmatic bronchioles exhibit disturbances in epithelial biology that produce MUC5AC-dominated mucus plugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral lung tissues from severe asthmatics, fatal asthmatics (FA), and controls were evaluated with histology, RNA in situ hybridization, and immunohistochemistry. Isolated bronchiolar and bronchial basal cell responses to IL13 were compared in culture. Spatial transcriptomics and multiplex immunophenotyping were performed on excised tissue sections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In excised tissues, severe and FA bronchiolar epithelia, depleted of distal airway secretory cells (DASCs) and enriched in MUC5AC goblet cells, circumscribed MUC5AC-dominated mucus plugs. In cultured bronchiolar basal cells, IL13 suppressed FOXA2 and DASC gene signatures and upregulated MUC5AC expression. Additional studies in severe and FA-excised tissues demonstrated that bronchiolar epithelia were populated by MUC5AC-expressing goblet cell niches heterogeneously distributed within single segments and, indeed, individual bronchioles. Spatial transcriptomics and immuno-proteomics of these MUC5AC-expressing bronchiolar niches identified increased goblet, suprabasal (SERPINB3), and basal cells, juxtaposed to a loss of DASC gene signatures. MUC5AC-high niche bronchiolar basal cells expressed reduced FOXA2 and elevated type-2 inflammatory (T2) gene signatures. Immune cell distributions surrounding asthmatic bronchioles differed from controls but did not correlate with MUC5AC-high niches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Asthmatic bronchioles exhibit a T2-driven proximalization associated with mucus plugging. MUC5AC-high niches were identified heterogeneously in bronchiolar epithelia independent of immune cell localizations, suggesting asthmatic bronchioles contain cellular niches which perpetuate T2-initiated epithelial remodeling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202409-1849oc","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:55:10Z","timestamp":1758642910000},"page":"209-226","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":11,"title":["Airway epithelial heterogeneity and mucus plugging in\u00a0asthmatic bronchioles"],"prefix":"10.1093","volume":"212","author":[{"given":"Stephen A","family":"Schworer","sequence":"first","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Rheumatology, Allergy, and Immunology, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Murano","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Dang","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0594","authenticated-orcid":false,"given":"Matthew R","family":"Markovetz","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Saito","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Kato","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Asakura","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney C","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C","family":"Morton","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Van Heusden","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chua","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Strickler","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoey Y","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Crisp","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayleigh A","family":"Doherty","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania","family":"Mastan","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto E","family":"Trejo Bittar","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany A","family":"Cody","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh Medical Center , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B","family":"Trudeau","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Pittsburgh Medical Center , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"De La Cruz","sequence":"additional","affiliation":[{"name":"Pathology Services Core, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M","family":"Ralph","sequence":"additional","affiliation":[{"name":"Pathology Services Core, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic B","family":"Askin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reynold A","family":"Panettieri","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, Rutgers Robert Wood Johnson Medical School , New Brunswick, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J","family":"Koziol-White","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, Rutgers Robert Wood Johnson Medical School , New Brunswick, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Byrd","sequence":"additional","affiliation":[{"name":"Division of Oral and Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry , Chapel Hill, NC,","place":["United States"]},{"name":"Department of Innovation & Technology Research, ADA Science & Research Institute , Gaithersburg, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Livraghi-Butrico","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda K","family":"O\u2019Neal","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-2841","authenticated-orcid":false,"given":"Scott H","family":"Randell","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally E","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Pittsburgh Medical Center , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Okuda","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C","family":"Boucher","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"2026030315473555900_aamaf058-B1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/S0140-6736(17)33311-1","article-title":"Asthma","volume":"391","author":"Papi","year":"2018","journal-title":"Lancet."},{"key":"2026030315473555900_aamaf058-B2","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1172\/JCI95693","article-title":"Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction","volume":"128","author":"Dunican","year":"2018","journal-title":"J Clin Invest."},{"key":"2026030315473555900_aamaf058-B3","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1164\/rccm.202110-2265OC","article-title":"Mucus plugs persist in asthma, and changes in mucus plugs associate with changes in airflow over time","volume":"205","author":"Tang","year":"2022","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B4","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1164\/rccm.202306-1102LE","article-title":"Effects of \u00addupilumab on mucus plugging and ventilation defects in patients with moderate-to-severe asthma: a randomized, double-blind, placebo-controlled trial","volume":"208","author":"Svenningsen","year":"2023","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B5","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1148\/radiol.2021204616","article-title":"Mucus plugs in asthma at CT associated with regional ventilation defects at 3He MRI","volume":"303","author":"Mummy","year":"2022","journal-title":"Radiology"},{"key":"2026030315473555900_aamaf058-B6","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1378\/chest.101.4.916","article-title":"Marked goblet cell hyperplasia with mucus accumulation in the \u00adairways of patients who died of severe acute asthma attack","volume":"101","author":"Aikawa","year":"1992","journal-title":"Chest"},{"key":"2026030315473555900_aamaf058-B7","doi-asserted-by":"publisher","first-page":"S184","DOI":"10.1513\/AnnalsATS.201807-485AW","article-title":"Autopsy and imaging studies of mucus in asthma. Lessons learned about disease mechanisms and the role of mucus in airflow obstruction","volume":"15","author":"Dunican","year":"2018","journal-title":"Ann Am Thorac Soc."},{"key":"2026030315473555900_aamaf058-B8","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/s0002-9343(03)00241-9","article-title":"Characterization of airway plugging in fatal asthma","volume":"115","author":"Kuyper","year":"2003","journal-title":"Am J Med."},{"key":"2026030315473555900_aamaf058-B9","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1152\/physrev.00023.2019","article-title":"Are we meeting the promise of endotypes and precision medicine in asthma?","volume":"100","author":"Ray","year":"2020","journal-title":"Physiol Rev"},{"key":"2026030315473555900_aamaf058-B10","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1165\/rcmb.2024-0082WS","article-title":"Asthma pathogenesis: phenotypes, therapies and gaps. Summary of the aspen lung conference 2023","volume":"71","author":"Sharma","year":"2024","journal-title":"Am J Respir Cell Mol Biol."},{"key":"2026030315473555900_aamaf058-B11","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1164\/rccm.201504-0763PP","article-title":"Evolving concepts of asthma","volume":"192","author":"Gauthier","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B12","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/S0140-6736(17)30879-6","article-title":"After asthma: redefining airways diseases","volume":"391","author":"Pavord","year":"2018","journal-title":"Lancet."},{"key":"2026030315473555900_aamaf058-B13","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1164\/rccm.201603-0526LE","article-title":"Abnormalities in MUC5AC and MUC5B protein in airway mucus in asthma","volume":"194","author":"Lachowicz-Scroggins","year":"2016","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B14","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1172\/JCI84910","article-title":"Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma","volume":"126","author":"Bonser","year":"2016","journal-title":"J Clin Invest."},{"key":"2026030315473555900_aamaf058-B15","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1164\/rccm.200903-0392OC","article-title":"T-helper type 2-driven inflammation defines major subphenotypes of asthma","volume":"180","author":"Woodruff","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030315473555900_aamaf058-B16","doi-asserted-by":"publisher","first-page":"1113100","DOI":"10.3389\/fphys.2023.1113100","article-title":"Airway remodeling heterogeneity in asthma and its relationship to disease outcomes","volume":"14","author":"Hsieh","year":"2023","journal-title":"Front Physiol"},{"key":"2026030315473555900_aamaf058-B17","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0186-2020","article-title":"Structure and function of small airways in asthma patients revisited","volume":"30","author":"van den Bosch","year":"2021","journal-title":"Eur Respir Rev."},{"key":"2026030315473555900_aamaf058-B18","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/j.1398-9995.2009.02242.x","article-title":"The small airways and distal lung compartment in asthma and COPD: a time for reappraisal","volume":"65","author":"Contoli","year":"2010","journal-title":"Allergy"},{"key":"2026030315473555900_aamaf058-B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12948-021-00147-8","article-title":"Small airway dysfunction and poor asthma control: a dangerous liaison","volume":"19","author":"Cottini","year":"2021","journal-title":"Clin Mol Allergy."},{"key":"2026030315473555900_aamaf058-B20","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S2213-2600(21)00536-1","article-title":"The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study","volume":"10","author":"Kraft","year":"2022","journal-title":"Lancet Respir Med"},{"key":"2026030315473555900_aamaf058-B21","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/S2213-2600(19)30049-9","article-title":"Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study","volume":"7","author":"Postma","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2026030315473555900_aamaf058-B22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S2213-2600(22)00185-0","article-title":"Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study","volume":"11","author":"Kole","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2026030315473555900_aamaf058-B23","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.anai.2018.08.009","article-title":"Is small airways dysfunction related to asthma control and type 2 inflammation?","volume":"121","author":"Kuo","year":"2018","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2026030315473555900_aamaf058-B24","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1146\/annurev-pathol-042220-015902","article-title":"The pathology of asthma: what is obstructing our view?","volume":"18","author":"Aegerter","year":"2023","journal-title":"Annu Rev Pathol"},{"key":"2026030315473555900_aamaf058-B25","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaip.2025.07.002","article-title":"Small airway dysfunction is an independent exacerbation risk biomarker in the mild, well-controlled asthmatic; a frequently unrecognized high-risk phenotype","author":"Galant","year":"2025","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2026030315473555900_aamaf058-B26","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.anai.2024.11.006","article-title":"Oscillometry-defined small airways dysfunction as a treatable trait in asthma","volume":"134","author":"Cottini","year":"2025","journal-title":"Ann Allergy Asthma Immunol."},{"key":"2026030315473555900_aamaf058-B27","doi-asserted-by":"publisher","first-page":"AB223","DOI":"10.1016\/j.jaci.2022.12.694","article-title":"Mucus plugging and regional heterogeneity are features of asthmatic small airways","volume":"151","author":"Schworer","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"2026030315473555900_aamaf058-B28","first-page":"A4535","author":"Schworer","year":"2023"},{"key":"2026030315473555900_aamaf058-B29","first-page":"A5015","author":"Schworer","year":"2024"},{"key":"2026030315473555900_aamaf058-B30","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1183\/16000617.0045-2015","article-title":"Should lung biopsies be performed in patients with severe asthma?","volume":"24","author":"Doberer","year":"2015","journal-title":"Eur Respir Rev"},{"key":"2026030315473555900_aamaf058-B31","doi-asserted-by":"publisher","first-page":"359ra132","DOI":"10.1126\/scitranslmed.aag1370","article-title":"Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation","volume":"8","author":"Cho","year":"2016","journal-title":"Sci Transl Med."},{"key":"2026030315473555900_aamaf058-B32","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1164\/rccm.201804-0734OC","article-title":"Localization of secretory mucins MUC5AC and MUC5B in normal\/healthy human airways","volume":"199","author":"Okuda","year":"2019","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B33","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1164\/rccm.202207-1384OC","article-title":"A unique cellular organization of human distal airways and its disarray in chronic obstructive pulmonary disease","volume":"207","author":"Rustam","year":"2023","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41586-022-04541-3","article-title":"Human distal lung maps and lineage hierarchies reveal a bipotent progenitor","volume":"604","author":"Kadur Lakshminarasimha Murthy","year":"2022","journal-title":"Nature"},{"key":"2026030315473555900_aamaf058-B35","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1164\/rccm.201608-1672OC","article-title":"Smoking-dependent distal-to-proximal repatterning of the adult human small airway epithelium","volume":"196","author":"Yang","year":"2017","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B36","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1164\/rccm.202008-3198OC","article-title":"Secretory cells dominate airway CFTR expression and function in human airway superficial epithelia","volume":"203","author":"Okuda","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030315473555900_aamaf058-B37","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1164\/rccm.200811-1768OC","article-title":"Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma","volume":"180","author":"Park","year":"2009","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B38","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1165\/rcmb.2018-0199OC","article-title":"The club cell marker SCGB1A1 downstream of FOXA2 is reduced in asthma","volume":"60","author":"Zhu","year":"2019","journal-title":"Am J Respir Cell Mol Biol."},{"key":"2026030315473555900_aamaf058-B39","doi-asserted-by":"publisher","first-page":"6133","DOI":"10.4049\/jimmunol.1000223","article-title":"Foxa2 programs Th2 cell-mediated innate immunity in the developing lung","volume":"184","author":"Chen","year":"2010","journal-title":"J Immunol"},{"key":"2026030315473555900_aamaf058-B40","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1164\/rccm.201101-0106OC","article-title":"Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation","volume":"184","author":"Maeda","year":"2011","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B41","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1242\/dev.00966","article-title":"Foxa2 regulates alveolarization and goblet cell hyperplasia","volume":"131","author":"Wan","year":"2004","journal-title":"Development."},{"key":"2026030315473555900_aamaf058-B42","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1164\/rccm.202202-0309OC","article-title":"Mucins MUC5AC and MUC5B are variably packaged in the same and in separate secretory granules","volume":"206","author":"Hoang","year":"2022","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B43","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","author":"Vieira Braga","year":"2019","journal-title":"Nat Med."},{"key":"2026030315473555900_aamaf058-B44","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1755-8794-5-21","article-title":"Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers","volume":"5","author":"Wang","year":"2012","journal-title":"BMC Med Genomics."},{"key":"2026030315473555900_aamaf058-B45","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41586-022-04552-0","article-title":"Human distal airways contain a multipotent secretory cell that can regenerate alveoli","volume":"604","author":"Basil","year":"2022","journal-title":"Nature"},{"key":"2026030315473555900_aamaf058-B46","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1164\/rccm.201408-1458OC","article-title":"Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease","volume":"191","author":"Christenson","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B47","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01962-2017","article-title":"Meta-analysis of airway epithelium gene expression in asthma","volume":"51","author":"Tsai","year":"2018","journal-title":"Eur Respir J."},{"key":"2026030315473555900_aamaf058-B48","doi-asserted-by":"publisher","first-page":"4566","DOI":"10.1038\/s41467-023-40173-5","article-title":"Guided construction of single cell reference for human and mouse lung","volume":"14","author":"Guo","year":"2023","journal-title":"Nat Commun."},{"key":"2026030315473555900_aamaf058-B49","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1038\/s41467-020-16239-z","article-title":"Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium","volume":"11","author":"Goldfarbmuren","year":"2020","journal-title":"Nat Commun."},{"key":"2026030315473555900_aamaf058-B50","doi-asserted-by":"publisher","DOI":"10.1242\/dev.177428","article-title":"Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures","volume":"146","author":"Ruiz Garc\u00eda","year":"2019","journal-title":"Development."},{"key":"2026030315473555900_aamaf058-B51","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jaci.2010.05.046","article-title":"Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma","volume":"126","author":"Thomas","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"2026030315473555900_aamaf058-B52","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1172\/JCI13557","article-title":"IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells","volume":"108","author":"Laoukili","year":"2001","journal-title":"J Clin Invest."},{"key":"2026030315473555900_aamaf058-B53","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1111\/cea.12843","article-title":"The role of human \u03b2-defensins in allergic diseases","volume":"46","author":"Niyonsaba","year":"2016","journal-title":"Clin Exp Allergy."},{"key":"2026030315473555900_aamaf058-B54","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jaci.2023.10.024","article-title":"Chemokine CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation","volume":"153","author":"Nakano","year":"2024","journal-title":"J Allergy Clin Immunol"},{"key":"2026030315473555900_aamaf058-B55","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1111\/all.13924","article-title":"Serum CXCL9 as a potential marker of Type 1 inflammation in the context of eosinophilic asthma","volume":"74","author":"Hasegawa","year":"2019","journal-title":"Allergy"},{"key":"2026030315473555900_aamaf058-B56","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1164\/rccm.202402-0403OC","article-title":"Type 1 immune responses related to viral infection influence corticosteroid response in asthma","volume":"211","author":"Fahy","year":"2025","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B57","doi-asserted-by":"publisher","DOI":"10.1172\/JCI186889","article-title":"Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence","volume":"135","author":"Liegeois","year":"2025","journal-title":"J Clin Invest."},{"key":"2026030315473555900_aamaf058-B58","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw4295","article-title":"Protein crystallization promotes type 2 immunity and is reversible by antibody treatment","volume":"364","author":"Persson","year":"2019","journal-title":"Science"},{"key":"2026030315473555900_aamaf058-B59","doi-asserted-by":"publisher","first-page":"e0229238","DOI":"10.1371\/journal.pone.0229238","article-title":"Changes in airway diameter and mucus plugs in patients with asthma exacerbation","volume":"15","author":"Yoshida","year":"2020","journal-title":"PLoS One"},{"key":"2026030315473555900_aamaf058-B60","doi-asserted-by":"publisher","DOI":"10.3390\/cells13231991","article-title":"Transcriptomic analysis of air-liquid interface culture in human lung organoids reveals regulators of epithelial differentiation","volume":"13","author":"Kim","year":"2024","journal-title":"Cells"},{"key":"2026030315473555900_aamaf058-B61","doi-asserted-by":"crossref","DOI":"10.1172\/JCI149336","article-title":"Basal epithelial stem cells cross an alarmin checkpoint for postviral lung disease","volume":"131","author":"Wu","year":"2021","journal-title":"J Clin Invest"},{"key":"2026030315473555900_aamaf058-B62","doi-asserted-by":"publisher","first-page":"3967","DOI":"10.1172\/JCI65570","article-title":"Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease","volume":"123","author":"Byers","year":"2013","journal-title":"J Clin Invest"},{"key":"2026030315473555900_aamaf058-B63","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1038\/s41467-022-28973-7","article-title":"Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology","volume":"13","author":"Sajuthi","year":"2022","journal-title":"Nat Commun"},{"key":"2026030315473555900_aamaf058-B64","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.jaci.2023.01.030","article-title":"Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling","volume":"151","author":"Wang","year":"2023","journal-title":"J Allergy Clin Immunol."},{"key":"2026030315473555900_aamaf058-B65","doi-asserted-by":"publisher","first-page":"5818","DOI":"10.1038\/s41467-024-50222-2","article-title":"Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes","volume":"15","author":"Yamada","year":"2024","journal-title":"Nat Commun."},{"key":"2026030315473555900_aamaf058-B66","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.174786","article-title":"Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease","volume":"9","author":"Raphael","year":"2024","journal-title":"JCI Insight."},{"key":"2026030315473555900_aamaf058-B67","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41586-018-0449-8","article-title":"Allergic inflammatory memory in human respiratory epithelial progenitor cells","volume":"560","author":"Ordovas-Montanes","year":"2018","journal-title":"Nature"},{"key":"2026030315473555900_aamaf058-B68","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1016\/j.jaci.2022.12.828","article-title":"A functional genomics pipeline to identify high-value asthma and allergy CpGs in the human methylome","volume":"151","author":"Morin","year":"2023","journal-title":"J Allergy Clin Immunol."},{"key":"2026030315473555900_aamaf058-B69","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1164\/rccm.201506-1243OC","article-title":"Genome-wide methylation study identifies an IL-13-induced epigenetic signature in asthmatic airways","volume":"193","author":"Nicodemus-Johnson","year":"2016","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B70","doi-asserted-by":"publisher","first-page":"107872","DOI":"10.1016\/j.celrep.2020.107872","article-title":"Single-cell and population transcriptomics reveal pan-epithelial remodeling in type 2-high asthma","volume":"32","author":"Jackson","year":"2020","journal-title":"Cell Rep."},{"key":"2026030315473555900_aamaf058-B71","doi-asserted-by":"publisher","first-page":"100229","DOI":"10.1016\/j.xgen.2022.100229","article-title":"Genomic characterization and therapeutic utilization of IL-13-responsive \u00adsequences in asthma","volume":"3","author":"Koh","year":"2023","journal-title":"Cell Genom."},{"key":"2026030315473555900_aamaf058-B72","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12931-025-03315-5","article-title":"Spatial \u00adphenotyping of human bronchial airways in obstructive lung disease","volume":"26","author":"Khalfaoui","year":"2025","journal-title":"Respir Res."},{"key":"2026030315473555900_aamaf058-B73","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/s41590-025-02161-3","article-title":"A single-cell spatial chart of the airway wall reveals proinflammatory cellular ecosystems and their interactions in health and asthma","volume":"26","author":"Joulia","year":"2025","journal-title":"Nat Immunol."},{"key":"2026030315473555900_aamaf058-B74","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1111\/all.15837","article-title":"Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis","volume":"78","author":"Soliai","year":"2023","journal-title":"Allergy"},{"key":"2026030315473555900_aamaf058-B75","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1172\/JCI123524","article-title":"HSP90 inhibitor geldanamycin reverts IL-13- and IL-17-induced airway goblet cell metaplasia","volume":"129","author":"Pezzulo","year":"2019","journal-title":"J Clin Invest."},{"key":"2026030315473555900_aamaf058-B76","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2332\/allergolint.55.329","article-title":"Elimination of IL-13 reverses established goblet cell metaplasia into ciliated epithelia in airway epithelial cell culture","volume":"55","author":"Kondo","year":"2006","journal-title":"Allergol Int."},{"key":"2026030315473555900_aamaf058-B77","doi-asserted-by":"publisher","first-page":"eabq6352","DOI":"10.1126\/sciimmunol.abq6352","article-title":"A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma","volume":"8","author":"Alladina","year":"2023","journal-title":"Sci Immunol."},{"key":"2026030315473555900_aamaf058-B78","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1513\/AnnalsATS.201411-507FR","article-title":"The role of surfactant in lung disease and host defense against pulmonary infections","volume":"12","author":"Han","year":"2015","journal-title":"Ann Am Thorac Soc."},{"key":"2026030315473555900_aamaf058-B79","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.3389\/fimmu.2018.01998","article-title":"The role of collectins and galectins in lung innate immune defense","volume":"9","author":"Casals","year":"2018","journal-title":"Front Immunol"},{"key":"2026030315473555900_aamaf058-B80","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1164\/rccm.202306-1093OC","article-title":"Proximal and distal bronchioles contribute to the pathogenesis of non-cystic fibrosis bronchiectasis","volume":"209","author":"Asakura","year":"2024","journal-title":"Am J Respir Crit Care Med."},{"key":"2026030315473555900_aamaf058-B81","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/s41591-021-01332-7","article-title":"Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition","volume":"27","author":"Carraro","year":"2021","journal-title":"Nat Med."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1164\/rccm.202409-1849OC\/66535871\/rccm.202409-1849oc.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/212\/2\/209\/66535871\/rccm.202409-1849oc.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/212\/2\/209\/66535871\/rccm.202409-1849oc.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T20:47:47Z","timestamp":1772570867000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/212\/2\/209\/8437440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":81,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,9,23]]},"published-print":{"date-parts":[[2026,2,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202409-1849oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2025,9,23]]},"assertion":[{"value":"2024-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}