Airway responsiveness to histamine and leukotriene E4 in subjects with aspirin-induced asthma.
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 mumol 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 mumol (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 PD 35 in the AIA group changed to 0.19 mumol (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 less than 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.
Arm
J P
JP
Department of Allergy and Allied Respiratory Disorders, UMDS, Guy's Hospital, London, United Kingdom.
O'Hickey
S P
SP
Spur
B W
BW
Lee
T H
TH
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D005260:Female; D006632:Histamine; D006801:Humans; D007975:Leukotriene B4; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D007975:Leukotriene B4; D006632:Histamine; D001241:Aspirin