Airway Responsiveness to Histamine and Leukotriene E4 in Subjects with Aspirin-induced Asthma

Authors:
  • SOStephen P. O'HIckey
    Stephen P. O'HIckey
  • BSBernd W. Spur
    Bernd W. Spur
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Abstract
Airway responsiveness to histamine and leukotriene E4 (LTE4) has been compared between five subjects with aspirin-induced asthma (AIA) and 15 asthmatic subjects without aspirin sensitivity (non-AIA). In the AIA group, the geometric mean doses of histamine and LTE4 causing a 35% fall in specific airway conductance (PD35) were 0.31 nmol and 0.17 nmol, respectively, and LTE4 was 1,870 times more potent than histamine. In the non-AIA group, the histamine and LTE4 PD35 doses were 0.40 nmol (non-AIA versus AIA, NS) and 2.8 nmol (non-AIA versus AIA, p = 0.002), respectively, and LTE4 was 145 times more potent than histamine in eliciting bronchoconstriction (non-AIA versus AIA, p = 0.001). After desensitization to aspirin the geometric mean histamine and LTE4 PD35 in the AIA group changed to 0.19 µmol (NS) and 3.3 nmol (p = 0.007), respectively, and there was an average 33-fold reduction in the responsiveness of the airways to LTE4 relative to histamine (p < 0.001). In five non-AIA subjects, ingestion of 600 mg of aspirin daily did not lead to any significant change in airway responsiveness to histamine or to LTE4. These results demonstrate a selective and marked increase in airway responsiveness to LTE4 in subjects with AIA. The efficacy of desensitization may relate in part to a selective down-regulation of LTE4 receptors within the airways.

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