Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.

Huang, D; Zhang, L; Liu, Y; Wang, J; Zhang, J; Baines, KJ; Liu, G; Hsu, AC-Y; Wang, F; Chen, Z; Oliver, BG; Xie, M; Qin, L; Liu, D; Wan, H; Luo, F; Li, W; Wang, G; Gibson, PG

Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.

Huang, D Zhang, L Liu, Y Wang, J Zhang, J Baines, KJ Liu, G

Hsu, AC-Y Wang, F Chen, Z Oliver, BG Xie, M Qin, L Liu, D Wan, H Luo, F Li, W Wang, G Gibson, PG

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Publisher:: ELSEVIER SCIENCE INC
Publication Type:: Journal Article
Citation:: Ann Allergy Asthma Immunol, 2024, 133, (1), pp. 64-72.e4
Issue Date:: 2024-07

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Field	Value	Language
dc.contributor.author	Huang, D
dc.contributor.author	Zhang, L
dc.contributor.author	Liu, Y
dc.contributor.author	Wang, J
dc.contributor.author	Zhang, J
dc.contributor.author	Baines, KJ
dc.contributor.author	Liu, G https://orcid.org/0000-0002-0489-2638
dc.contributor.author	Hsu, AC-Y
dc.contributor.author	Wang, F
dc.contributor.author	Chen, Z
dc.contributor.author	Oliver, BG
dc.contributor.author	Xie, M
dc.contributor.author	Qin, L
dc.contributor.author	Liu, D
dc.contributor.author	Wan, H
dc.contributor.author	Luo, F
dc.contributor.author	Li, W
dc.contributor.author	Wang, G
dc.contributor.author	Gibson, PG
dc.date.accessioned	2024-11-25T01:22:47Z
dc.date.available	2024-03-11
dc.date.available	2024-11-25T01:22:47Z
dc.date.issued	2024-07
dc.identifier.citation	Ann Allergy Asthma Immunol, 2024, 133, (1), pp. 64-72.e4
dc.identifier.issn	1081-1206
dc.identifier.issn	1534-4436
dc.identifier.uri	http://hdl.handle.net/10453/182096
dc.description.abstract	BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009529 (http://www.chictr.org.cn).
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER SCIENCE INC
dc.relation	Lung Foundation Australia
dc.relation.ispartof	Ann Allergy Asthma Immunol
dc.relation.isbasedon	10.1016/j.anai.2024.03.009
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.subject	1107 Immunology
dc.subject.classification	Allergy
dc.subject.classification	3204 Immunology
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Acetylcholine
dc.subject.mesh	Asthma
dc.subject.mesh	Cytokines
dc.subject.mesh	Disease Progression
dc.subject.mesh	Inflammation
dc.subject.mesh	Non-Neuronal Cholinergic System
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Severity of Illness Index
dc.subject.mesh	Sputum
dc.subject.mesh	Sputum
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Disease Progression
dc.subject.mesh	Inflammation
dc.subject.mesh	Acetylcholine
dc.subject.mesh	Cytokines
dc.subject.mesh	Severity of Illness Index
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Non-Neuronal Cholinergic System
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Acetylcholine
dc.subject.mesh	Asthma
dc.subject.mesh	Cytokines
dc.subject.mesh	Disease Progression
dc.subject.mesh	Inflammation
dc.subject.mesh	Non-Neuronal Cholinergic System
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Severity of Illness Index
dc.subject.mesh	Sputum
dc.title	Activated non-neuronal cholinergic system correlates with non-type 2 inflammation and exacerbations in severe asthma.
dc.type	Journal Article
utslib.citation.volume	133
utslib.location.activity	United States
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 Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
utslib.copyright.status	embargoed	*
utslib.copyright.embargo	2025-07-01T00:00:00+1000Z
dc.date.updated	2024-11-25T01:22:45Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	133
utslib.citation.issue	1

Abstract:

BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009529 (http://www.chictr.org.cn).

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http://hdl.handle.net/10453/182096