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Eur Respir J 2002; 19:872-878
Copyright ©ERS Journals Ltd 2002


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

A.A. Acuña1, J. Gabrijelcic1, E.M. Uribe1, R. Rabinovich1, J. Roca1, J.A. Barberà1, K.F. Chung2 and R. Rodriguez-Roisin1

1 Servei de Pneumologia i Allèrgia Respiratòria, Institut Clínic de Pneumologia i Cirurgia Toràcica, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Departament de Medicina, Universitat de Barcelona, Barcelona, Spain. 2 National Heart and Lung Institute, Imperial College School of Medicine, London, UK

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

Keywords: chronic airway diseases, inflammatory mediators, inhaled glucocorticosteroids, neutrophil kinetics, pulmonary gas exchange

Received: August 3, 2001
Accepted December 10, 2001

This study was supported by Grant 99/0135 from the Fondo de Investigación Sanitaria (FIS) and the Comissionat per a Universitats i Recerca de la Generalitat de Catalunya (1999 SGR0228), and a grant-in-aid from GlaxoSmithKline (Research and Development, Greenford, Middlesex, UK and Madrid, Spain). A.A. Acuña was supported by Fundación Gran Mariscal de Ayacucho, Caracas, Venezuela and Instituto de Cooperación Iberoamericana (ICI), Spain. E.M. Uribe was supported by GlaxoSmithKline, Argentina.

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.




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