Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma

Abstract

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.

Formoterol protects against platelet-activating factor-induced effects in asthma

“…Anthropometric and functional data were within normal limits and close to those reported in previous studies [15]. There were no differences between the placebo and the formoterol subjects (table 2 and fig.…”

“…In contrast, formoterol was unable to modulate either facial flushing or neutrophil kinetics. Based on previous work by the authors in both normal subjects [3,8,9] and mild asthmatics [4,10,15], the authors postulate that PAF-induced pulmonary gas exchange defects and increases of Rrs are related to airway narrowing secondary to abnormally increased microvascular leakage, rather than to a primary constrictor effect on airway smooth muscle. SABAs were among the first agents to exhibit anti-oedema effects by preventing separation of endothelial cells at postcapillary venular sites [16].…”

Levalbuterol Inhibits Human Airway Smooth Muscle Cell Proliferation: Therapeutic Implications in the Management of Asthma

“…In this study, we found that activation of the PAF-receptor-mediated signaling pathway may be one mechanism by which (S) -albuterol induces HBSMC proliferation. PAF is an endogenous lipid mediator with mitogenic properties [40, 41], and has been reported to aggravate asthmatic conditions [42,43,44,45]. In our study, the specific PAF receptor antagonist CV-3988, at a low concentration of 1 µ M , inhibited (S) -albuterol-induced cell growth, but neither reversed levalbuterol-induced inhibition of cell growth, nor produced additive inhibition with levalbuterol.…”

Vasoconstriction after inhalation of budesonide: A study in the isolated and perfused rat lung

“…However, fewer clinical studies have addressed a possible effect of ICS on the pulmonary circulation. In asthmatics, inhalation of platelet aggregation factor (PAF) has been used for acute induction of a perfusion-ventilation mismatch in asthmatics [19]. Within 45 minutes after inhalation of fluticasone propionate, the corticosteroid ameliorated the PAF induced gas exchange mismatch, measured as improved systemic arterial oxygen tension.…”