Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy.

Liu, Y; Zhang, L; Li, HL; Liang, BM; Wang, J; Zhang, X; Chen, ZH; Zhang, HP; Xie, M; Wang, L; Wang, G; Oliver, BG

Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy.

Liu, Y Zhang, L Li, HL Liang, BM Wang, J Zhang, X Chen, ZH Zhang, HP Xie, M Wang, L Wang, G Oliver, BG

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Publisher:: KARGER
Publication Type:: Journal Article
Citation:: Respiration, 2021, 100, (8), pp. 767-779
Issue Date:: 2021

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Field	Value	Language
dc.contributor.author	Liu, Y
dc.contributor.author	Zhang, L
dc.contributor.author	Li, HL
dc.contributor.author	Liang, BM
dc.contributor.author	Wang, J
dc.contributor.author	Zhang, X
dc.contributor.author	Chen, ZH
dc.contributor.author	Zhang, HP
dc.contributor.author	Xie, M
dc.contributor.author	Wang, L
dc.contributor.author	Wang, G
dc.contributor.author	Oliver, BG
dc.date.accessioned	2022-03-25T05:15:19Z
dc.date.available	2021-02-15
dc.date.available	2022-03-25T05:15:19Z
dc.date.issued	2021
dc.identifier.citation	Respiration, 2021, 100, (8), pp. 767-779
dc.identifier.issn	0025-7931
dc.identifier.issn	1423-0356
dc.identifier.uri	http://hdl.handle.net/10453/155577
dc.description.abstract	BACKGROUND: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. OBJECTIVES: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25-75%), with clinical and inflammatory profile and treatment responsiveness in asthma. METHOD: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. RESULTS: SAD subjects had more elevated ΔVAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (p < 0.05), and Spearman partial correlation found FEF25-75% significantly related to IFN-γ and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (p = 0.022 and p = 0.032). CONCLUSIONS: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	KARGER
dc.relation.ispartof	Respiration
dc.relation.isbasedon	10.1159/000515328
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	This is the accepted manuscript version of an article published by S. Karger AG in [Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy. Respiration 100, 8 p767
dc.subject	1102 Cardiorespiratory Medicine and Haematology
dc.subject.classification	Respiratory System
dc.subject.mesh	Adult
dc.subject.mesh	Asthma
dc.subject.mesh	Bronchial Hyperreactivity
dc.subject.mesh	Bronchial Provocation Tests
dc.subject.mesh	Cross-Sectional Studies
dc.subject.mesh	Dyspnea
dc.subject.mesh	Female
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Humans
dc.subject.mesh	Interferon-gamma
dc.subject.mesh	Interleukin-8
dc.subject.mesh	Male
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Severity of Illness Index
dc.subject.mesh	Sputum
dc.subject.mesh	Treatment Failure
dc.subject.mesh	Visual Analog Scale
dc.title	Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy.
dc.type	Journal Article
utslib.citation.volume	100
utslib.location.activity	Switzerland
utslib.for	1102 Cardiorespiratory Medicine and Haematology
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	*
dc.date.updated	2022-03-25T05:15:17Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	100
utslib.citation.issue	8

Abstract:

BACKGROUND: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. OBJECTIVES: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25-75%), with clinical and inflammatory profile and treatment responsiveness in asthma. METHOD: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. RESULTS: SAD subjects had more elevated ΔVAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (p < 0.05), and Spearman partial correlation found FEF25-75% significantly related to IFN-γ and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (p = 0.022 and p = 0.032). CONCLUSIONS: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy.

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http://hdl.handle.net/10453/155577