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Dysregulation of mediator release in relation to bronchial asthma and bronchial hyperresponsiveness.

The hypothesis studied is that an increased responsiveness in asthma is not limited to the airways. 40 asthmatic children were analysed for their bronchial responsiveness (BR) to exercise. 20 patients revealed bronchial obstruction after exercise while the remainder did not. These parameters were compared to the responsiveness of leucocytes, which was determined by their histamine "releasability". 20 healthy children served as controls. Release of histamine induced by calciumionophore aided calcium influx was significantly higher in both groups of asthmatics than in the healthy children (P less than 0.005). Similar findings were obtained by induction of microtubule aggregation due to deuterium oxide (D2O). The S-shaped dose-response relationship with D2O was shifted to the left in the patients with BR to exercise compared to patients without (P less than 0.025). It is concluded that the mean "releasability" of histamine from leucocytes is higher if BR increases. The histamine release due to both stimulants correlated well (P less than 0.01). This suggests that the "releasability" is determined by the responsiveness of the microtubules. To a large degree this may also apply to allergen-induced histamine release, as was revealed from studies with anti-IgE The differences in histamine release found in relation to BR due to exercise were also present if the patients were divided according to BR due to histamine.