Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways.

Wen, H; Kole, T; Carpaij, OA; Karp, T; Guryev, V; Faiz, A; Chung, KF; Bhavsar, P; Adcock, IM; Siddiqui, S; Lan, A; Raby, KL; Zounemat-Kermani, N; Brightling, C; Singh, D; Kocks, J; Kraft, M; Beghé, B; Rabe, KF; Papi, A; Hylkema, MN; Nawijn, MC; van den Berge, M

Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways.

Wen, H Kole, T Carpaij, OA Karp, T Guryev, V Faiz, A

Chung, KF Bhavsar, P Adcock, IM Siddiqui, S Lan, A Raby, KL Zounemat-Kermani, N Brightling, C Singh, D Kocks, J Kraft, M Beghé, B Rabe, KF Papi, A Hylkema, MN Nawijn, MC van den Berge, M

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Allergy, 2026, 81, (9), pp. 3197-3205
Issue Date:: 2026-09

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Field	Value	Language
dc.contributor.author	Wen, H
dc.contributor.author	Kole, T
dc.contributor.author	Carpaij, OA
dc.contributor.author	Karp, T
dc.contributor.author	Guryev, V
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Chung, KF
dc.contributor.author	Bhavsar, P
dc.contributor.author	Adcock, IM
dc.contributor.author	Siddiqui, S
dc.contributor.author	Lan, A
dc.contributor.author	Raby, KL
dc.contributor.author	Zounemat-Kermani, N
dc.contributor.author	Brightling, C
dc.contributor.author	Singh, D
dc.contributor.author	Kocks, J
dc.contributor.author	Kraft, M
dc.contributor.author	Beghé, B
dc.contributor.author	Rabe, KF
dc.contributor.author	Papi, A
dc.contributor.author	Hylkema, MN
dc.contributor.author	Nawijn, MC
dc.contributor.author	van den Berge, M
dc.date.accessioned	2026-10-09T01:53:58Z
dc.date.available	2026-01-23
dc.date.available	2026-10-09T01:53:58Z
dc.date.issued	2026-09
dc.identifier.citation	Allergy, 2026, 81, (9), pp. 3197-3205
dc.identifier.issn	0105-4538
dc.identifier.issn	1398-9995
dc.identifier.uri	http://hdl.handle.net/10453/196635
dc.description.abstract	BACKGROUND: Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways. METHODS: In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427). RESULTS: We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity. CONCLUSION: The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation.ispartof	Allergy
dc.relation.isbasedon	10.1111/all.70283
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Allergy
dc.subject.classification	3204 Immunology
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Transcriptome
dc.subject.mesh	Male
dc.subject.mesh	Adult
dc.subject.mesh	Nasal Mucosa
dc.subject.mesh	Middle Aged
dc.subject.mesh	Bronchi
dc.subject.mesh	Biomarkers
dc.title	Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways.
dc.type	Journal Article
utslib.citation.volume	81
utslib.location.activity	Denmark
utslib.for	1107 Immunology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated	2026-10-09T01:53:57Z
pubs.issue	9
pubs.publication-status	Published
pubs.volume	81
utslib.citation.issue	9

Abstract:

BACKGROUND: Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways. METHODS: In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427). RESULTS: We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity. CONCLUSION: The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.

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http://hdl.handle.net/10453/196635