Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man

Summary The reproducibility of acute effects of inhaled PAF on airway calibre, circulating neutrophil count and any subsequent increase in bronchial responsiveness has been studied in six normal subjects and compared to the effects of inhaled lyso-PAF, the inactive precursor and metabolite of PAF. PAF caused acute bronchoconstriction and a transient fall in neutrophil count on two separate occasions in five out of six subjects (minimum percentage of baseline values (mean): first PAF challenge; sGaw 69%, Vmax30 72%; neutrophil count 70%; second PAF challenge; sGaw 61 %, Vmax30 74%, neutrophil count 63%). In one subject inhaled PAF caused bronchoconstriction and a transient fall in neutrophil count once, but a second challenge resulted in no detectable changes. There was no significant increase in bronchiai responsiveness to methacholine in any subject studied on five occasions over a 2-week period following each PAF challenge. Challenge with lyso-PAF did not cause acute effects or any subsequent changes in bronchial responsiveness. These findings demonstrate that any effects of inhaled PAF on bronchial responsiveness in normal man are small and probably not of clinical significance. It would also be inappropriate to use this human model to study the mechanisms of bronchial hyperresponsiveness or for the preliminary assessment of potential new anti-asthma drugs.