MECHANISMS OF INCREASED AIRWAY MICROVASCULAR PERMEABILITY - ROLE IN AIRWAY INFLAMMATION AND OBSTRUCTION

1. Airway inflammation is a signal feature of human asthma, as is bron chial obstruction and the resultant airflow limitation. An obligatory accompaniment to airway inflammation is increased airway microvascular permeability, which in turn is causally related to bronchial oedema. In this review, we have attempted to describe the mechanisms of increa sed airway microvascular permeability and its relationship to oedema, bronchial obstruction and the hyperreactivity to spasmogenic stimuli w hich are such common features of asthma. 2. It is now clear that bronc hial obstruction in chronic asthma can involve bronchial wall oedema a nd swelling in addition to reversible, elevated airway smooth muscle t one, mucus hypersecretion and airway plugging and potentially permanen t structural changes in airway architecture. Inflammatory mediators re leased in the airway wall in asthma including histamine, platelet-acti vating factor, leukotrienes and bradykinin are potent inducers of incr eased bronchial microvascular permeability and are thus promoters of b ronchial oedema, airway wall swelling and reduction in luminal calibre . 3. The primary mechanism believed to underlie acute increases in mic rovascular permeability is contraction of postcapillary venular endoth elial cells, resulting in the formation of gaps between otherwise tigh tly associated cells. Extravasated plasma distributes to the interstit ial spaces in the airway wall, resulting in oedema and swelling, but m ay also traverse the epithelium and collect in the airway lumen. 4. Lu minal plasma may compromise epithelial integrity and cilial function a nd thus reduce mucus clearance. Plasma proteins may also promote the p roduction of viscous mucus and the formation of luminal mucus plugs. T ogether, these effects can result in or contribute to airway obstructi on and hyperresponsiveness.5. An understanding of such mechanisms can provide insight concerning novel and effective anti-asthma therapies.