{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:28:58Z","timestamp":1790285338558,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Asthma is a heterogeneous disease with various inflammatory subtypes, including the type\u20102 (T2) endotype associated with airway eosinophilia. Severe asthma is linked to reduced ventilatory function due to airway structural changes. This study compared the extent of airway remodeling in different immunological endotypes of asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Severe asthma patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a030) were stratified based on bronchial expression of T2 (e.g., <jats:italic>CST1<\/jats:italic>) and T3 (e.g., <jats:italic>IL1<\/jats:italic>7A) immunity genes as T2\u2010high, T3\u2010high, or low\u2010inflammatory. We analyzed airway wall thickness using endobronchial ultrasound (EBUS), bronchial biopsy morphometry, and mRNA expression of remodeling genes. Bronchial epithelial cell cultures were used to assess cytokine responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T2\u2010high asthma patients showed lower predicted FEV1 (59 vs. 74 % in low\u2010inflammatory variant, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.049) and increased submucosa layer (L2) in EBUS (0.203 vs. 0.189\u00a0mm, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.018). T2\u2010high asthma patients also had increased airway smooth muscle (ASM) mass (\u223c2\u2010fold, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.018) and marginally thicker reticular basement membrane. T3\u2010high asthma showed only a trend toward thicker L2 (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.055). Only patients with an eosinophilic signature in endobronchial biopsy demonstrated increased expression of remodeling genes, including <jats:italic>TGFB1<\/jats:italic>. A profibrotic profile was also induced in bronchial epithelium stimulated in vitro with IL\u201013.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data suggest that T2\u2010signature in severe asthma is associated with increased ASM mass and more pronounced airway obstruction. Overexpression of remodeling genes primarily occurred in patients with signs of eosinophilic infiltration in the bronchial mucosa, suggesting that remodeling may progress with uncontrolled airway inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.70060","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T03:50:15Z","timestamp":1749786615000},"source":"Crossref","is-referenced-by-count":9,"title":["Type 2 gene expression signature in severe asthma associates with more advanced airway remodeling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0444-981X","authenticated-orcid":false,"given":"Bogdan","family":"Jakiela","sequence":"first","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"G\u00f3rka","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Gross\u2010Sondej","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u0142awomir","family":"Mikrut","sequence":"additional","affiliation":[{"name":"Faculty of Mining Surveying and Environmental Engineering AGH University of Science and Technology  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Oko\u0144","sequence":"additional","affiliation":[{"name":"Department of Pathology Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Department of Pathology Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Andrychiewicz","sequence":"additional","affiliation":[{"name":"Department of Endoscopy University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Plutecka","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Stachura","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Bochenek","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanis\u0142awa","family":"Bazan\u2010Socha","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"S\u0142adek","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-6675","authenticated-orcid":false,"given":"Jerzy","family":"Soja","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine Jagiellonian University Medical College  Krak\u00f3w Poland"},{"name":"Department of Pulmonology and Allergology University Hospital  Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101936"},{"key":"e_1_2_9_3_1","unstructured":"Global Initiative for Asthma.Global Strategy for Asthma Management and Prevention.https:\/\/ginasthma.org\/"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.25"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00146905"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010012414\u2010040343"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810223391703"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201411\u20101958OC"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12119"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.326.7386.422"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07\u20100713"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9868704"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9812110"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200903\u20100392OC"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0183\u20102021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23968"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201512\u20102452OC"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax\u20102023\u2010220972"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab3142"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.969243"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202111\u20102634OC"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707413104"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002568"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017\u20100162OC"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01962\u20102017"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.10.029"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136284"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08\u20102759"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02135\u20102016"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02298\u20102016"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.11.009"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.01.008"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00247.2010"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006\u20100172OC"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13727"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.07.003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00068\u20102019"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2022.806391"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.119411"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064281"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084086"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.3.2733"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.2.9609066"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.15.3.8810646"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016\u20100307TR"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2021.100547"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00165106"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200807\u20101126OC"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax\u20102021\u2010217032"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.12.019"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13986"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.6.8520757"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200603\u2010352OC"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.52.4.372"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01836\u20102020"}],"container-title":["Clinical and Translational Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clt2.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:57:26Z","timestamp":1750924646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clt2.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":54,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/clt2.70060"],"URL":"https:\/\/doi.org\/10.1002\/clt2.70060","archive":["Portico"],"relation":{},"ISSN":["2045-7022","2045-7022"],"issn-type":[{"value":"2045-7022","type":"print"},{"value":"2045-7022","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"article-number":"e70060"}}