Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Karp, T; Faiz, A; van Nijnatten, J; Kerstjens, HAM; Boudewijn, I; Kraft, M; Vonk, JM; Nawijn, MC; Heijink, IH; Beghé, B; Rabe, KF; Papi, A; Brightling, C; Singh, D; van der Molen, T; Siddiqui, S; Christenson, S; Guryev, V; van den Berge, M

Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Karp, T Faiz, A

van Nijnatten, J Kerstjens, HAM Boudewijn, I Kraft, M Vonk, JM Nawijn, MC Heijink, IH Beghé, B Rabe, KF Papi, A Brightling, C Singh, D van der Molen, T Siddiqui, S Christenson, S Guryev, V van den Berge, M

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Publisher:: BMJ PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Thorax, 2024, 79, (10), pp. 905-914
Issue Date:: 2024-09-18

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Field	Value	Language
dc.contributor.author	Karp, T
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	van Nijnatten, J
dc.contributor.author	Kerstjens, HAM
dc.contributor.author	Boudewijn, I
dc.contributor.author	Kraft, M
dc.contributor.author	Vonk, JM
dc.contributor.author	Nawijn, MC
dc.contributor.author	Heijink, IH
dc.contributor.author	Beghé, B
dc.contributor.author	Rabe, KF
dc.contributor.author	Papi, A
dc.contributor.author	Brightling, C
dc.contributor.author	Singh, D
dc.contributor.author	van der Molen, T
dc.contributor.author	Siddiqui, S
dc.contributor.author	Christenson, S
dc.contributor.author	Guryev, V
dc.contributor.author	van den Berge, M
dc.date.accessioned	2024-12-20T04:58:02Z
dc.date.available	2024-06-18
dc.date.available	2024-12-20T04:58:02Z
dc.date.issued	2024-09-18
dc.identifier.citation	Thorax, 2024, 79, (10), pp. 905-914
dc.identifier.issn	0040-6376
dc.identifier.issn	1468-3296
dc.identifier.uri	http://hdl.handle.net/10453/182733
dc.description.abstract	INTRODUCTION: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma. METHODS: We analysed nasal epithelial gene expression data from 369 patients with asthma and 58 non-asthmatic controls from the Assessment of Small Airways Involvement in Asthma study. Unsupervised hierarchical clustering was performed on asthma-associated genes. Asthma-associated gene signatures were replicated in independent cohorts with nasal and bronchial brushes data by comparing Gene Set Variation Analysis scores between asthma patients and non-asthmatic controls. RESULTS: We identified 67 higher expressed and 59 lower expressed genes in nasal epithelium from asthma patients compared with controls (false discovery rate<0.05), including CLCA1, CST1 and POSTN, genes well known to reflect asthma in bronchial airway epithelium. Hierarchical clustering revealed several molecular asthma endotypes with distinct clinical characteristics, including an endotype with higher blood and sputum eosinophils, high fractional exhaled nitric oxide, and more severe small airway dysfunction, as reflected by lower forced expiratory flow at 50%. In an independent cohort, we demonstrated that genes higher expressed in the nasal epithelium reflect asthma-associated changes in the lower airways. CONCLUSION: Our results show that the nasal epithelial gene expression profile reflects asthma-related processes in the lower airways. We suggest that nasal epithelium may be a useful non-invasive tool to identify asthma endotypes and may advance personalised management of the disease.
dc.format	Electronic
dc.language	eng
dc.publisher	BMJ PUBLISHING GROUP
dc.relation.ispartof	Thorax
dc.relation.isbasedon	10.1136/thorax-2023-221230
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	1103 Clinical Sciences
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3202 Clinical sciences
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Male
dc.subject.mesh	Nasal Mucosa
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Adult
dc.subject.mesh	Phenotype
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Gene Expression
dc.subject.mesh	Nasal Mucosa
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Gene Expression
dc.subject.mesh	Phenotype
dc.subject.mesh	Adult
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Male
dc.subject.mesh	Nasal Mucosa
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Adult
dc.subject.mesh	Phenotype
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Gene Expression
dc.title	Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.
dc.type	Journal Article
utslib.citation.volume	79
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
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	in_progress	*
dc.date.updated	2024-12-20T04:58:00Z
pubs.issue	10
pubs.publication-status	Published online
pubs.volume	79
utslib.citation.issue	10

Abstract:

INTRODUCTION: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma. METHODS: We analysed nasal epithelial gene expression data from 369 patients with asthma and 58 non-asthmatic controls from the Assessment of Small Airways Involvement in Asthma study. Unsupervised hierarchical clustering was performed on asthma-associated genes. Asthma-associated gene signatures were replicated in independent cohorts with nasal and bronchial brushes data by comparing Gene Set Variation Analysis scores between asthma patients and non-asthmatic controls. RESULTS: We identified 67 higher expressed and 59 lower expressed genes in nasal epithelium from asthma patients compared with controls (false discovery rate<0.05), including CLCA1, CST1 and POSTN, genes well known to reflect asthma in bronchial airway epithelium. Hierarchical clustering revealed several molecular asthma endotypes with distinct clinical characteristics, including an endotype with higher blood and sputum eosinophils, high fractional exhaled nitric oxide, and more severe small airway dysfunction, as reflected by lower forced expiratory flow at 50%. In an independent cohort, we demonstrated that genes higher expressed in the nasal epithelium reflect asthma-associated changes in the lower airways. CONCLUSION: Our results show that the nasal epithelial gene expression profile reflects asthma-related processes in the lower airways. We suggest that nasal epithelium may be a useful non-invasive tool to identify asthma endotypes and may advance personalised management of the disease.

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http://hdl.handle.net/10453/182733