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

• Published in: Free radical biology & medicine 2022-05, Vol.185, p.97-119
• Main Authors: Saunders, Ruth M., Biddle, Michael, Amrani, Yassine, Brightling, Christopher E.
• Format: Article
• Language: English
• Subjects: Air pollutants; Asthma - drug therapy; Bronchi - metabolism; Cigarette smoke; Humans; Inflammatory mediators; Muscle, Smooth; Myocytes, Smooth Muscle - metabolism; Nrf2/HO-1 signalling; Oxidative Stress; Pulmonary Disease, Chronic Obstructive - metabolism; Reactive Oxygen Species - metabolism; Therapeutics
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.04.011

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. [Display omitted] •Airway smooth muscle (ASM) is dysfunctional in asthma and COPD.•Cigarette smoke, pollutants, aero-allergens and mediators induce oxidative stress in ASM.•Nrf2/HO-1 antioxidant defences are compromised in ASM in asthma and by TGF-β.•ASM dysfunction relevant to asthma and COPD is increased by oxidative stress stimuli.•Oxidative stress effects on ASM could contribute to AHR, airflow obstruction and inflammation.