Leukotriene bronchoconstriction induced by allergen and exercise.

Abstract

Airway hyperresponsiveness to a wide variety of bronchoconstrictor agonists is a characteristic finding in patients with current, symptomatic asthma. The agonists include inhaled pharmacological agonists, such as histamine (1) acting on airway H 1 receptors, the cholinergic agonist methacholine (2) acting on airway M 3 receptors, the cysteinyl-leukotrienes (3) acting on airway Cys-LT 1 receptors, and the stimulatory prostaglandins (PG)D 2 (4) and PGF 2a (5) likely acting on airway TP receptors. These agonists are considered to be direct stimuli causing bronchoconstriction in individuals with asthma, because their action is directly on specific airway receptors. Airway hyperresponsiveness is also present to a number of physical stimuli such as exercise (6), isocapnic hyperventilation of cold, dry air (7), and hypo- and hypertonic aerosols (8). The bronchoconstriction that develops after exposure to the physical stimuli is indirect, because it occurs through the release of constrictor mediators from cells within the airways, which subsequently act on their specific receptors to mediate bronchoconstriction. Another important indirect stimulus for bronchoconstriction in many individuals with asthma is environmental allergens. The responses after inhaled allergens are often quite different from those after the other indirect stimuli, in that the acute bronchoconstrictor responses are often followed by the development of late-phase bronchoconstrictor responses (9), airway inflammation (10), and an increase in airway hyperresponsiveness (11). The focus of this article is to evaluate the evidence that the cysteinyl-leukotrienes (LT) C 4 , D 4 , and E 4 are released in asthmatic airways and are the main cause of bronchoconstriction after exposure to exercise and environmental allergens, and of the changes in airway hyperresponsiveness after the inhalation of allergen.