Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.