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

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.

Mechanisms by Which <i>S</i>-Albuterol Induces Human Bronchial Smooth Muscle Cell Proliferation

“…PAF is an endogenous lipid mediator with mitogenic properties [37] and has been reported to aggravate asthmatic conditions [38, 39]. We found that S -albuterol, but neither racemic albuterol nor levalbuterol, induced the expression of PAF receptor protein by the smooth muscle cells.…”

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.…”

Platelet-Activating Factor and Evidence of Oxidative Stress in the Bronchoalveolar Fluid of Thoroughbred Colts during Race Training

“…Platelet‐activating factor (PAF; 1‐ O ‐alkyl‐2‐acetyl‐ sn ‐glycero‐3‐phosphocoline) is a potent proinflammatory mediator implicated in angiogenesis, atherosclerosis, anaphylaxis, and endotoxemia 7,8 . PAF is also involved in a variety of lung functions, such as airway and vascular tone, ciliary beating frequency, and endothelial permeability, resulting in gas exchange impairment 9,10 . In horse airways, PAF participates in the pathophysiology of recurrent airway obstruction (RAO), leading to an increased recruitment and activation of neutrophils and eosinophils in the lung, as well as disturbances in the respiratory function 11 …”

“…7,8 PAF is also involved in a variety of lung functions, such as airway and vascular tone, ciliary beating frequency, and endothelial permeability, resulting in gas exchange impairment. 9,10 In horse airways, PAF participates in the pathophysiology of recurrent airway obstruction (RAO), leading to an increased recruitment and activation of neutrophils and eosinophils in the lung, as well as disturbances in the respiratory function. 11 RAO is closely related to environmental factors, 12,13 but the contribution of the different environmental and stable factors, as etiological components of the airway inflammation of young athletic horses, awaits clarification.…”