Bronchial asthma is characterized by airways
inflammation and airways hyperresponsiveness. It is unlikely that the pathophysiology of
asthma and bronchial hyperresponsiveness can be explained on the basis of a single cell or a single class of mediators. Nevertheless, the possibility that
leukotrienes may contribute to the pathogenesis of the inflammatory, vasoactive ans spasmogenic components of
bronchial asthma is suggested by the properties of these
lipid mediators, the preferential capacity of inflammatory cells to generate
leukotrienes and the presence of
leukotrienes in the airways of asthmatic subjects. The sulphidopeptide
leukotrienes are potent bronchoconstrictor agonists when inhaled. The airways of asthmatic subjects are hyperresponsive to
leukotrienes as to other bronchoconstrictor agonists. Nevertheless, the airways responsiveness of asthmatic subjects to these agonists demonstrate several unusual properties. While the airways of asthmatic subjects are relatively less responsive to
LTC4 and
LTD4, compared to agents such as
histamine or
methacholine, they demonstrate a marked and selective hyperresponsiveness to
LTE4, suggesting a possibly unique role for this mediator in the pathogenesis of airways hyperresponsiveness. In addition an increased sensitivity of the airways to
LTE4 may contribute to the mechanism of
aspirin-induced asthma. The capacity of the sulphidopeptide
leukotrienes to increase the airways responsiveness of normal subjects to
methacholine and of asthmatic subjects to
histamine is further evidence for a role for these substances in the pathogenesis of
bronchial asthma.