The Changing Face of Asthma

Abstract

Asthma may affect 5 to 10 per cent of the population, yet remains underdiagnosed and undertreated. It is probably the only common treatable condition whose prevalence and severity is increasing [1,2] and there is evidence from several countries that mortality has risen, despite advances in therapy [3,4]. In New Zealand the problem has reached epidemic proportions and asthma is now one of the commonest causes of death in young people [5]. Even in the United States, which was unaffected by the epidemic of asthma deaths in the 1960s, there are now indications that the mortality from asthma may be rising [6]. These alarming statistics should encourage greater effort to be put into elucidating the pathogenesis of asthma. Several advances have recently been made in elucidating the mechanisms of asthma and this should eventually lead to more effective treatment. Bronchial hyperresponsiveness, an exaggerated bronchoconstrictor response to many different stimuli, is a key feature of asthma, and relates more closely to the severity of asthma and the frequency of symptoms than does resting lung function [7]. To determine the cause of asthma it is necessary to understand the mechanisms of bronchial hyperresponsiveness, and effective control of asthma symptoms implies a reduction in bronchial responsiveness. Increased bronchial responsiveness follows exposure to allergens, upper respiratory tract infection, and certain industrial chemicals. There is now considerable experimental evidence that induced hyperresponsiveness in animals is associated with inflammation of the airways [8]. Histopathological studies from asthmatic patients who have died during asthma attacks show marked inflammation in the airways, with infiltration of inflammatory cells, particularly eosinophils, disruption of airway epithelium and plugging of the airway lumen by viscous mucus [9]. Similar, but less severe, pathological changes have also been described in bronchial biopsies from asthmatics with relatively mild disease [10] and this supports the experimental evidence that airway inflammation may underly bronchial hyperresponsiveness. Bronchial microvascular leakage is also a typical feature, leading to oedema of the submucosa and extravasation of plasma which may be linked to bronchial hyperresponsiveness [11]. The previously held view that asthma could be explained by release of mast cell mediators which cause bronchospasm must now be modified. It now seems likely that several different cells are involved in the pathogenesis of asthma, and that these cells produce a variety of mediators which interact in a complex way to produce a number of pathological effects which, together, contribute to bronchial hypeiTesponsiveness and the clinical features of asthma. Recent advances have been made by recognition of the different cells and inflammatory mediators participating in asthma, and of the neural mechanisms which may contribute to or modify these inflammatory events.