Smooth muscle hypercontractility in airway hyperresponsiveness: innate, acquired, or nonexistent?

Asthma symptoms are triggered or exacerbated by a range of environmental factors, such as allergens, viruses, fungi, exercise, aspirin, pollutants, and occupational irritants and sensitizers. While traditionally considering an intrinsic disease, in more recent years asthma has been viewed by many as a genetically associated environmental lung disorder with a heterogeneous pathogenesis. With the exception of the severe cases, the diagnostic signature of asthma is the reversibility of airway obstruction by agents that relax airway smooth muscle (ASM), which attests to the importance of this tissue in the pathobiology of the airflow obstruction. Most asthmatic individuals are hyperresponsive to bronchoprovocative challenge with a spasmogen (i.e., bronchoconstrictor agonist such as methacholine or histamine). Airway hyperresponsiveness (AHR) in asthmatic patients can either result from “hyperreactive airways” characterized by an excessive airway narrowing or “hyperexcitability,” where the airways become excessively sensitive to very low doses of constrictor agonists. It is believed that the abnormal narrowing of the airways (hyperreactivity) is responsible for most of the morbidity and mortality due to asthma. In either case, the role of ASM in the development of AHR remains to be further investigated. The controversial questions that remain to be answered are whether AHR seen in asthmatic patients is due to functional changes in the ASM and whether those changes actually lead a “hypercontractile” phenotype. This special issue aims to shed light on what seems to be a perdurable debate as to whether the hypercontractility of ASM characterizes AHR, whether this hypercontractile phenotype exists, and whether it is innate or acquired. Notwithstanding the potentially important associative role of airway inflammation, this special issue addresses different viewpoints by experts in the field that relate to newly identified contractile properties of ASM that may contribute to AHR when perturbed and also considers the latest advances in the search for better asthma treatments that directly target the ASM. C. D. Pascoe and coworkers set the stage for the ongoing debate by providing an enlighten historical perspective on the role that has been attributed to ASM in the pathobiology of asthma and AHR. The authors reference monographs that date backs to the 16th century and then describe pivotal developments made more recently that offer tentative links between the airway dysfunction seen in asthma and certain recognized features of ASM observed ex vivo. They also point out the rapid gain of interest and the increasing amount of research pursued in this area in the past few years.