Airway smooth muscle function in asthma

Abstract

Known to have affected around 340 million people across the world in 2018, asthma is a prevalent chronic inflammatory disease of the airways. The symptoms such as wheezing, dyspnea, chest tightness, and cough reflect episodes of reversible airway obstruction. Asthma is a heterogeneous disease that varies in clinical presentation, severity, and pathobiology, but consistently features airway hyperresponsiveness (AHR)—excessive airway narrowing due to an exaggerated response of the airways to various stimuli. Airway smooth muscle (ASM) is the major effector of exaggerated airway narrowing and AHR and many factors may contribute to its altered function in asthma. These include genetic predispositions, early life exposure to viruses, pollutants and allergens that lead to chronic exposure to inflammatory cells and mediators, altered innervation, airway structural cell remodeling, and airway mechanical stress. Early studies aiming to address the dysfunctional nature of ASM in the etiology and pathogenesis of asthma have been inconclusive due to the methodological limitations in assessing the intrapulmonary airways, the site of asthma. The study of the trachealis, although convenient, has been misleading as it has shown no alterations in asthma and it is not as exposed to inflammatory cells as intrapulmonary ASM. Furthermore, the cartilage rings offer protection against stress and strain of repeated contractions. More recent strategies that allow for the isolation of viable intrapulmonary ASM tissue reveal significant mechanical differences between asthmatic and non-asthmatic tissues. This review will thus summarize the latest techniques used to study ASM mechanics within its environment and in isolation, identify the potential causes of the discrepancy between the ASM of the extra- and intrapulmonary airways, and address future directions that may lead to an improved understanding of ASM hypercontractility in asthma.

SFRP5 Partially Inhibits the Proliferation and Migration of Airway Smooth Muscle Cells in Children with Asthma by Regulating the Wnt/β-Catenin Signaling Pathway

“…Asthma is a chronic respiratory tract involving many cell types and components, and its pathogenesis has not yet been clarified [17]. Repeated asthma attacks will aggravate the injury of airway endothelial tissue, and the pathological manifestation is excessive proliferation of smooth muscle cells, leading to airway stenosis, increasing airway hyperresponsiveness, and inducing airway remodeling [18]. The pathological characteristics of airway remodeling mainly showed smooth muscle cell hyperplasia, goblet cell hyperplasia, airway spasm reversibility decreased and gradually weakened to disappear, and lung function index decreased [19].…”

Percent Recovery Index Predicts Poor Asthma Control and Exacerbation in Adults

“…The inherent property of ASM is one of the main mechanisms of AHR, and it plays important roles in acute exacerbation of asthma. 24 , 25 In asthmatic ASM, these inherent properties include increased mass and hypercontractility, which present as an increase in the maximum capacity and velocity of shortening. 24 In addition to inherent properties, ASM is also affected by inflammation or neuroendocrine factors in the asthmatic state.…”

TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes Ca2+ and Na+ Influx

“…This contractile tissue plays a crucial role in the lungs, anatomically and functionally [ 1 , 2 , 3 ]. In response to physiological and pathological stimuli, ASM contraction influences the diameter and resistance of the airways by regulating airflow, thereby enhancing or impairing ventilation [ 2 , 4 , 5 , 6 ]. Moreover, it also assists with defensive reflexes, such as coughing [ 5 , 7 ].…”

“…In response to physiological and pathological stimuli, ASM contraction influences the diameter and resistance of the airways by regulating airflow, thereby enhancing or impairing ventilation [ 2 , 4 , 5 , 6 ]. Moreover, it also assists with defensive reflexes, such as coughing [ 5 , 7 ]. Numerous lung disorders, such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and asthma, have been associated with the dysfunction of the ASM [ 2 , 8 , 9 , 10 , 11 , 12 ].…”

“…Alterations in the number and size of ASM cells and their contractile activity (i.e., excessive constriction and reduced relaxation) can lead to airway remodeling, hyperreactivity, and inflammation [ 9 , 10 , 11 , 13 ]. Several mechanisms are responsible for these changes, including signaling pathways mediated by G protein-coupled receptor (GPCR) and nonselective cationic channels (NSCCs) such as store-operated Ca 2+ (SOC) channels, transient receptor potential (TRP) channels, and stretch-activated channels [ 5 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”