Airway microvascular permeability in asthma: a target for drug action?

Evidence is presented that inflammatory mediators likely to be involved in asthma can increase the permeability of airway microvessels to macromolecules (i.e. cause leakage). The microvessels involved are in the tracheobronchial circulation, which supplies the trachea and bronchi. The acute response to these mediators has been shown to involve interendothelial gap formation in postcapillary venules. In animals, leakage can be demonstrated histologically using macromolecular tracers such as colloidal carbon. Alternatively, it can be detected by measuring the amount of radiolabelled, or fluorescein-labelled, plasma protein, or similar macromolecules, in airway tissue and/or airway lumen. There is clinical evidence to support a leakage response in asthmatic lung. Data are available suggesting that anti-asthma drugs can decrease airway microvascular leakage in animals and this can also be deduced from some of the clinical studies in asthmatics. The importance of airway microvascular leakage, and hence of plasma exudate, in the pathophysiology of asthma is stressed and possible ways of attenuating it with drugs are summarised.