ABSTRACT
Introduction
Asthma is characterized by enhanced airway contractility and remodeling where airway smooth muscle (ASM) plays a key role, modulated by inflammation. Understanding the mechanisms by which ASM contributes to these features of asthma is essential for the development of novel asthma therapies.
Areas covered
Inflammation in asthma contributes to a multitude of changes within ASM including enhanced airway contractility, proliferation, and fibrosis. Altered intracellular calcium ([Ca2+]i) regulation or Ca2+ sensitization contributes to airway hyperreactivity. Increased airway wall thickness from ASM proliferation and fibrosis contributes to structural changes seen with asthma.
Expert opinion
ASM plays a significant role in multiple features of asthma. Increased ASM contractility contributes to hyperresponsiveness, while altered ASM proliferation and extracellular matrix production promote airway remodeling both influenced by inflammation of asthma and conversely even influencing the local inflammatory milieu. While standard therapies such as corticosteroids or biologics target inflammation, cytokines, or their receptors to alleviate asthma symptoms, these approaches do not address the underlying contribution of ASM to hyperresponsiveness and particularly remodeling. Therefore, novel therapies for asthma need to target abnormal contractility mechanisms in ASM and/or the contribution of ASM to remodeling, particularly in asthmatics resistant to current therapies.
Article highlights
Despite therapeutic advances, asthma significantly impacts patients’ lives and overall healthcare
Increased insight into mechanisms contributing to asthma has broadened therapeutic options and allowed for more goal-oriented therapies
Therapeutic advances of drug delivery have broadened the potential targets of drug delivery and allowed for improved combined therapeutics
These advances have improved treatment options for asthmatics but also demonstrated future needs
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Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
All authors contributed equally to this review.