Formoterol protects against platelet-activating factor-induced effects in asthma.
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 beta2-agonists on PAF-induced disturbances have been consistently shown, those of long-acting beta2-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 microg), in a double-blind, placebo-controlled, crossover design following PAF (18 microg) inhalation. Compared with the placebo, at 5 min, premedication with formoterol reduced PAF-induced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V'A/Q') inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index of V'A/Q' 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.
Gabrijelcic
J
J
Servei de Pneumologia i Al.lèrgia Respiratòria (ICPCT), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
Casas
A
A
Rabinovich
R A
RA
Roca
J
J
Barberà
J A
JA
Chung
K F
KF
Rodríguez-Roisin
R
R
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D003371:Cough / Q000517:prevention & control; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000517:prevention & control; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005483:Flushing / Q000517:prevention & control; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000517:prevention & control; D010972:Platelet Activating Factor / Q000009:adverse effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D010972:Platelet Activating Factor; D000068759:Formoterol Fumarate