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Stressed out- The role of oxidative stress in airway smooth muscle dysfunction in asthma and COPD

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journal contribution
posted on 29.07.2022, 16:43 authored by Ruth M Saunders, Michael Biddle, Yassine Amrani, Christopher E Brightling
The airway smooth muscle (ASM) surrounding the airways is dysfunctional in both asthma and chronic obstructive pulmonary disease (COPD), exhibiting; increased contraction, increased mass, increased inflammatory mediator release and decreased corticosteroid responsiveness. Due to this dysfunction, ASM is a key contributor to symptoms in patients that remain symptomatic despite optimal provision of currently available treatments. There is a significant body of research investigating the effects of oxidative stress/ROS on ASM behaviour, falling into the following categories; cigarette smoke and associated compounds, air pollutants, aero-allergens, asthma and COPD relevant mediators, and the anti-oxidant Nrf2/HO-1 signalling pathway. However, despite a number of recent reviews addressing the role of oxidative stress/ROS in asthma and COPD, the potential contribution of oxidative stress/ROS-related ASM dysfunction to asthma and COPD pathophysiology has not been comprehensively reviewed. We provide a thorough review of studies that have used primary airway, bronchial or tracheal smooth muscle cells to investigate the role of oxidative stress/ROS in ASM dysfunction and consider how they could contribute to the pathophysiology of asthma and COPD. We summarise the current state of play with regards to clinical trials/development of agents targeting oxidative stress and associated limitations, and the adverse effects of oxidative stress on the efficacy of current therapies, with reference to ASM related studies where appropriate. We also identify limitations in the current knowledge of the role of oxidative stress/ROS in ASM dysfunction and identify areas for future research.

Funding

NIHR

History

Author affiliation

NIHR Leicester Biomedical Research Centre

Version

VoR (Version of Record)

Published in

FREE RADICAL BIOLOGY AND MEDICINE

Volume

185

Pagination

97 - 119

Publisher

ELSEVIER SCIENCE INC

issn

0891-5849

eissn

1873-4596

Acceptance date

19/04/2022

Copyright date

2022

Available date

29/07/2022

Language

English