Role of airway smooth muscle in asthma: Possible relation to the neuroendocrine system

Abstract

Though not yet firmly established, it appears likely that the neuroendocrine system (NES) regulates airway smooth muscle function. As it is the latter which is altered in asthma, the importance of the role of the NES in this disease is clear. The fact that transmitters from the NE cells are released from their basal aspect, and are in close proximity to the subjacent airway smooth muscle, further indicates an interaction. The question then arises as to what are the experimental desiderata for conducting studies of the ASM. These should constitute what Sergei Sorokin has called the "Koch's postulates of airway smooth muscle research." As human tissues from asthmatics are difficult to obtain, animal models have been developed. The requirements are that, in these animals, the allergy be IgE based, that a congenital or familial factor be operative, that a noncholinergic nonadrenergic inhibitory system be a component of the neural regulatory system, and that the antigen for immunization be of a type commonly found in human asthmatics. Ideally, evidence of clinical asthma and exercise-induced asthma and nocturnal attacks should also be present. Unfortunately, no ideal animal models exist and one cannot talk about asthmatic animals, but only of animals with allergic bronchospasm. If in vitro research is to be conducted, there are additional requirements. The tissue should be from a relevant location. The tracheal smooth muscle which has been the favorite, purely because of its convenience, is not a good model. For the early asthmatic attack, central bronchi (3-5 mm diameter) should be used. Muscle strips obtained from them should be parallel-fibred and the cartilage plaques should be carefully dissected away, otherwise they contribute unwanted frictional forces when velocity is measured. Care should be taken to ensure that the epithelial cell layer is intact, as evidence indicates that it may regulate airway muscle function, though this has not been established for all the animal species used in asthma research. The isolated muscle strip should be in a steady state, particularly with respect to the functional variable under study, before definitive data are collected. Most importantly, it is shortening capacity that must be studied, as this is the in vitro analogue to in vivo narrowing of airways. Isometric force development provides information about wall stiffness and is of very little relevance to the elucidation of the mechanism of bronchospasm.(ABSTRACT TRUNCATED AT 400 WORDS)

Asthma: a comparison of animal models using stereological methods

“…It is not known whether these differences are due to co-exposure to air pollution, a phenotypic difference in myocytes by airway level or differences in the impact of the allergen response on different stages of post-natal airway development. Increases in airway smooth muscle may increase airway contractility as is found in airway hyperresponsiveness [97,98] and in airways taken from asthmatic patients [99]. The same is true for infant rhesus monkeys with allergic airways disease, which also exhibit altered orientation and increases in muscle bundle mass [100].…”