Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro

Rutting, S; Xenaki, D; Reddy, KD; Baraket, M; Chapman, DG; King, GG; Oliver, BG; Tonga, KO

Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro

Rutting, S Xenaki, D Reddy, KD Baraket, M Chapman, DG King, GG Oliver, BG Tonga, KO

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Publisher:: European Respiratory Society
Publication Type:: Journal Article
Citation:: ERJ Open Research, 2021, 7, (2), pp. 1-4
Issue Date:: 2021-04-15

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Field	Value	Language
dc.contributor.author	Rutting, S
dc.contributor.author	Xenaki, D
dc.contributor.author	Reddy, KD
dc.contributor.author	Baraket, M
dc.contributor.author	Chapman, DG
dc.contributor.author	King, GG
dc.contributor.author	Oliver, BG
dc.contributor.author	Tonga, KO
dc.date.accessioned	2022-01-08T03:45:59Z
dc.date.available	2021-03-25
dc.date.available	2022-01-08T03:45:59Z
dc.date.issued	2021-04-15
dc.identifier.citation	ERJ Open Research, 2021, 7, (2), pp. 1-4
dc.identifier.issn	2312-0541
dc.identifier.issn	2312-0541
dc.identifier.uri	http://hdl.handle.net/10453/152828
dc.description.abstract	Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge. Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FAO
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	European Respiratory Society
dc.relation.ispartof	ERJ Open Research
dc.relation.isbasedon	10.1183/23120541.00117-2021
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-01-08T03:45:57Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	7
utslib.citation.issue	2

Abstract:

Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge. Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FAO

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http://hdl.handle.net/10453/152828