Effects of platelet activating factor on airway calibre, airway responsiveness, and circulating cells in asthmatic subjects.

The effects of inhaled platelet activating factor were compared with those of inhaled methacholine (control) on airway calibre, airway responsiveness to methacholine and isoprenaline, and circulating cells in eight subjects with mild, stable asthma. Platelet activating factor was given in six doses at 15 minute intervals and airway response measured as change in partial expiratory flow at 30% of vital capacity (Vp30). Platelet activating factor caused a fall in Vp30, the mean (SEM) maximum percentage fall being 28.9 (4.2) five minutes after the first dose (12 micrograms) and 50.9 (8.0) after the second dose (24 micrograms). Tachyphylaxis occurred, however, with the four subsequent doses of inhaled platelet activating factor. There was transient neutropenia after the first dose, from a mean of 3.6 (0.2) x 10(9) to 2.2 (0.5) x 10(9) neutrophils/l; this response also showed tachyphylaxis with subsequent doses. The mean PC40 (the concentration of methacholine needed to cause a 40% fall in Vp30) was unchanged one, three, and seven days after administration of platelet activating factor. There was no significant correlation between baseline PC40 methacholine and the maximal fall in Vp30 after either the first (12 micrograms) or the second dose (24 micrograms) of platelet activating factor. The control challenge with methacholine produced a degree of bronchoconstriction similar to that of platelet activating factor but was not associated with any significant change in bronchial responsiveness or in circulating cells. The bronchodilator response to inhaled isoprenaline measured three days after inhalation of platelet activating factor and of methacholine was similar after the two challenges. Thus asthmatic subjects who are hyperresponsive to methacholine show a similar bronchoconstrictor response to platelet activating factor, as has been observed in normal subjects; overall this did not cause airway hyperresponsiveness to methacholine.