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

¹ Servei de Pneumologia i Al.lèrgia Respiratòria (ICPCT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. ² Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK

CORRESPONDENCE: R. Rodriguez-Roisin, Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clínic, Villarroel, 170, 08036 Barcelona, Spain. Fax: 34 932275404. E-mail: roisin@medicina.ub.es

Keywords: airway obstruction, bronchial challenge, gas exchange, inflammatory mediators, long-acting ß₂-agonists

Received: May 26, 2003
Accepted September 2, 2003

This study was supported by grants 00/0617 from the Fondo de Investigación Sanitaria (FIS), 2001 SGR00286 from the Comissionat per a Universitats i Recerca de la Generalitat de Catalunya, Red de Centros (2003-C03/11) del Ministerio de Sanidad y Consumo (ISCIII), and by grants-in-aid by AstraZeneca, Farmacéutica Spain, and Esteve Group.

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 ß₂-agonists on PAF-induced disturbances have been consistently shown, those of long-acting ß₂-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 µg), in a double-blind, placebo-controlled, crossover design following PAF (18 µg) 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.

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				E. Polverino, F. P. Gomez, H. Manrique, N. Soler, J. Roca, J. A. Barbera, and R. Rodriguez-Roisin Gas Exchange Response to Short-Acting beta2-Agonists in Chronic Obstructive Pulmonary Disease Severe Exacerbations Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 350 - 355. [Abstract] [Full Text] [PDF]