Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man.
Platelet activating factor (PAF), a phospholipid inflammatory mediator, was given as an aerosol to eight normal subjects. PAF caused a dose-dependent bronchoconstriction in all subjects. This did not correlate well with responsiveness to methacholine. Some subjects showed tachyphylaxis to PAF-induced bronchoconstriction. No subject had a late bronchoconstriction response. Transient facial flushing and an increase in heart rate (mean 7 beats/min) occurred but there was no consistent change in blood pressure. Lyso-PAF, the inactive precursor and major metabolite of PAF, had no effect on pulmonary or cardiovascular responses. Six of the subjects took part in a double-blind, randomised, placebo-controlled, crossover study in which bronchial responsiveness to methacholine was measured over the 3 days after administration of PAF or lyso-PAF. PAF had a greater effect in raising responsiveness (p less than 0.01). Its maximum effect occurred at 3 days and returned to baseline in 1 to 4 weeks. PAF may contribute to the pathogenesis of bronchial hyperresponsiveness, which is the most characteristic abnormality in asthma.
Cuss
F M
FM
Dixon
C M
CM
Barnes
P J
PJ
D000328:Adult; D000336:Aerosols; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008176:Lung Volume Measurements; D008297:Male; D008688:Methacholine Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010972:Platelet Activating Factor; D011897:Random Allocation; D013997:Time Factors
D000336:Aerosols; D008688:Methacholine Compounds; D010972:Platelet Activating Factor