Platelet-activating factor (PAF)-induced neutrophil lung sequestration may require cell surface adhesion molecules (macrophage-1 antigen (MAC-1) and lymphocyte function-associated antigen-1 (LFA-1)). In this randomised, double-blinded, crossover study, the neutrophil kinetics after PAF and Lyso-PAF (L-PAF) airway challenge were investigated in nine mild-intermittent asthmatics.Neutrophils were measured in peripheral blood (PB) before and at 5, 15, 45 and 240 min after bronchoprovocation, and in induced sputum before and at 240 min after challenge. MAC-1 and LFA-1 expression were assessed by immunocytochemistry, and leukotriene B 4 (LTB 4 ) was measured by enzyme-immunoassay in induced-sputum supernatants.Compared with baseline, neutrophils in PB decreased 5 min after PAF, while at 240 min neutrophils in induced sputum increased. Compared with baseline and L-PAF, PAF decreased the percentages of MAC-1-and LFA-1-positive neutrophils in PB at 5 min, but increased the percentages of MAC-1 and LFA-1 in neutrophil-induced sputum. Moreover, compared with baseline and L-PAF, PAF-induced sputum revealed higher LTB 4 levels, a finding that correlated with the elevated number of neutrophils in induced sputum.These findings suggest that macrophage-1 antigen and lymphocyte functionassociated antigen-1 are involved in platelet-activating factor-induced neutrophil lung traffic, and that this process is modulated by enhanced leukotriene B 4 release within the airways.

Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage.This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge.Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93¡4 mmHg; P: 83¡4 mmHg) at 45 min, without influencing the increases in Rrs.In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.

No abstract

Platelet-activating factor (PAF) is an inflammatory mediator that provokes neutropaenia, bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways. While the inhibitory effects of short-acting b 2 -agonists on PAF-induced disturbances have been consistently shown, those of longacting b 2 -agonists are less convincing.To further explore the mechanisms involved in PAF challenge in asthma, 12 patients (forced expiratory volume in one second, 90¡4% predicted) were investigated 2 h after inhaled formoterol (18 mg), in a double-blind, placebo-controlled, crossover design following PAF (18 mg) inhalation.Compared with the placebo, at 5 min, premedication with formoterol reduced PAFinduced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V9A/Q9) inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index of V9A/Q9 heterogeneity (by 71%). In contrast, PAF-induced facial flushing, neutropaenia and subsequent rebound neutrophilia remained unchanged.The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect, in addition to its class effects, an anti-exudative effect of formoterol in the airways. Eur Respir J 2004; 23: 71-75.

Z dokumentom želimo smernice, ki jih predlaga GINA, vključiti v slovenski prostor. Želimo, da bi dokument služil enotnemu in dogovorjenemu pristopu k obravnavi bolnikov z astmo na primarni in specialistični pulmološki ravni.