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

Abstract

1. Airway inflammation is a signal feature of human asthma, as is bronchial 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 increased airway microvascular permeability and its relationship to oedema, bronchial obstruction and the hyperreactivity to spasmogenic stimuli which are such common features of asthma. 2. It is now clear that bronchial obstruction in chronic asthma can involve bronchial wall oedema and swelling in addition to reversible, elevated airway smooth muscle tone, mucus hypersecretion and airway plugging and potentially permanent structural changes in airway architecture. Inflammatory mediators released in the airway wall in asthma including histamine, platelet-activating factor, leukotrienes and bradykinin are potent inducers of increased bronchial microvascular permeability and are thus promoters of bronchial oedema, airway wall swelling and reduction in luminal calibre. 3. The primary mechanism believed to underlie acute increases in microvascular permeability is contraction of post-capillary venular endothelial cells, resulting in the formation of gaps between otherwise tightly associated cells. Extravasated plasma distributes to the interstitial spaces in the airway wall, resulting in oedema and swelling, but may also traverse the epithelium and collect in the airway lumen. 4. Luminal plasma may compromise epithelial integrity and cilial function and thus reduce mucus clearance. Plasma proteins may also promote the production of viscous mucus and the formation of luminal mucus plugs. Together, these effects can result in or contribute to airway obstruction and hyper-responsiveness. 5. An understanding of such mechanisms can provide insight concerning novel and effective anti-asthma therapies.