Attenuation of platelet-activating factor induced bronchoconstriction by nedocromil sodium.
We assessed the effect of nedocromil sodium on bronchoconstriction and airway responsiveness induced by platelet-activating factor (PAF) in eight normal subjects, in a double-blind, placebo-controlled cross-over study. Subjects inhaled PAF by a dosimeter method in 5 doses of 18 micrograms each, separated by an interval of 15 min, (total dose of 90 micrograms). Airway calibre was measured by partial expiratory flow at 30% of vital capacity (Vp30) before and at 1, 3, 5, 10 and 15 min after each dose of PAF. The bronchoconstrictor response was assessed by measuring the area under the curve of the percentage fall in Vp30 over time. There was a significant reduction in PAF-induced bronchoconstriction after nedocromil sodium (1,225 +/- 392 arbitrary units; mean +/- SEM) compared to placebo (2,395 +/- 598; p < 0.01). There was no significant difference in the fall in peripheral neutrophil count measured at 5 min after PAF with nedocromil sodium (48.5 +/- 9.5%) compared to placebo (43.3 +/- 6.8%). In conclusion, nedocromil sodium significantly attenuates PAF-induced bronchoconstriction but not the peripheral neutropenia in normal subjects. Since PAF is not a direct constrictor of human airway smooth muscle, this effect of nedocromil sodium may indicate inhibition of release of bronchoconstrictor mediators.
Hayes
J P
JP
Dept of Thoracic Medicine, Royal Brompton National Heart and Lung Hospital, London, UK.
Chung
K F
KF
Barnes
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil