New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma.
Recent studies have suggested that inflammation may play an important role in the characteristic bronchial hyperresponsiveness and symptoms of chronic asthma. The mechanisms by which inflammatory cells, mediators, and nerves interact to produce the features of asthma are still uncertain, however. Although mast cells play an important role in the immediate response to allergen (and probably exercise), pharmacologic evidence argues against a critical role in the late response or bronchial hyperresponsiveness in which other cells, such as macrophages and eosinophils, may play a more important role. Many mediators have been implicated in asthma, but only PAF causes a prolonged increase in bronchial responsiveness. PAF attracts eosinophils into tissues and potently activates these cells, which may lead to epithelial damage, a key feature of asthmatic airways. PAF is also a potent inducer of microvascular leakage in airways, which may result in submucosal edema and plasma exudation into the airway lumen in the future. PAF antagonists will reveal whether PAF plays an important role in the eosinophilic inflammation of asthma. Neural mechanisms may also make an important contribution. Inflammatory mediators may influence neurotransmitter release from airway nerves, and neurotransmitters may be proinflammatory. Neural control is complex and cholinergic, adrenergic, and NANC mechanisms may contribute to bronchial hyperresponsiveness. Many neuropeptides, which may be the transmitters of NANC nerves, have been identified in airways. Neuropeptides in airway sensory nerves, such as substance P, have potent proinflammatory effects and, if these are released by an axon reflex, may amplify the inflammatory response in asthma. Since asthma may be chronic eosinophilic bronchitis, it is logical that the primary treatment should involve drugs that suppress this inflammatory response. At present, corticosteroids appear to be the most effective therapy; they have potent effects against eosinophils and macrophages (but not on mast cells) and reduce bronchial hyperresponsiveness and symptoms. By contrast, bronchodilators, such as beta-agonists, although they reduce symptoms, do not reduce the chronic inflammatory response or bronchial hyperresponsiveness and may mask the underlying inflammation. New therapies should be directed toward controlling eosinophil infiltration and activation in airways.
Barnes
P J
PJ
Department of Thoracic Medicine, Brompton Hospital, London, England.
D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology