SALBUTAMOL REDUCES PULMONARY NEUTROPHIL SEQUESTRATION OF PLATELET-ACTIVATING-FACTOR IN HUMANS

To investigate whether salbutamol inhibits platelet-activating factor (PAF)-induced neutrophil sequestration in the lungs, we studied eight nonatopic, nonsmoking, healthy subjects (six men; aged 27.0 +/- 1.5 (S E) yr) with PAF-induced bronchial response. Prior to PAF challenge (24 mu g), they inhaled either salbutamol (300 mu g) or placebo in a rand omized, double-blind, crossover manner two weeks apart. Respiratory sy stem resistance (Rrs), arterial blood gases, and neutrophil counts wer e measured 4, 8, 12 and 30 min after PAF. Neutrophil kinetics in the l ungs were assessed by tracking autologous Tc-99m-erythrocytes and (111 )ln-neutrophils. Compared with salbutamol, arterial blood neutrophil c ounts fell (p < 0.04) maximally at 4 min after PAF, followed by a mild rebound neutrophilia, whereas Rrs increased (p < 0.01) and Pa-o2 decr eased (p < 0.05) at 4 min only. The intrapulmonary activity of (111)ln -neutrophils after pretreatment with placebo was higher compared with salbutamol (1.98 +/- 0.15 versus 1.33 +/- 0.23 cps/mCi/pixel) (p < 0.0 1) although both their initial sequestration (first-pass) and subseque nt washout were not significantly different. Inhaled salbutamol blocks pulmonary neutrophil sequestration and lung function abnormalities fo llowing PAF challenge in humans.