Am. J. Respir. Crit. Care Med., Volume 156, Number 1, July 1997, 17-22

Inhibition of PAF-induced Gas Exchange Defects by Beta-adrenergic Agonists in Mild Asthma Is Not Due to Bronchodilation

ORLANDO DÍAZ, JOAN A. BARBERÁ, RAMÓN MARRADES, K. FAN CHUNG, JOSEP ROCA, and ROBERT RODRIGUEZ-ROISIN

Serveis de Pneumologia i Al.lèrgia Respiratòria, Departament de Medicina, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; and National Heart and Lung Institute, Imperial College, School of Medicine, London, United Kingdom

Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated whether the salbutamol-induced improvement in gas exchange disturbances after PAF is the result of bronchodilation by comparing this effect with that of ipratropium bromide. We hypothesized that ipratropium bromide, an anticholinergic agent without vascular effects, should block PAF-induced bronchoconstriction but not interfere with its systemic, neutropenic, and gas exchange effects. We studied eight nonsmokers with mild asthma (26 ± 2.0 SE yr of age) who, prior to PAF challenge (18 µg), inhaled either ipratropium bromide (80 µg) or salbutamol (300 µg) in a randomized, double-blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory system resistance (Rrs), arterial blood gases and ventilation-perfusion ( A/) inequalities were measured 5, 15, and 45 min after PAF. Compared with pretreatment with salbutamol, ipratropium bromide also blocked the increase of respiratory system resistance (Rrs) but did not prevent facial flushing and neutropenia (p < 0.03) at 5 min nor the decrease of Pa_O2 (p = 0.08 and 0.05), the increase of AaPO₂ (p < 0.02 each), and the deterioration of A/ relationships (p < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar to that observed previously in normal subjects and in nonpremedicated asthmatic patients after PAF, with return to baseline values at 45 min. By contrast, salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF-induced abnormalities. These findings indicate that, in patients with mild asthma, salbutamol inhibits PAF- induced neutropenia and gas exchange abnormalities by mechanisms involving other than airway smooth muscle narrowing, possibly by acting on both the bronchial and pulmonary circulations. Díaz O, Barberà JA, Marrades R, Chung KF, Roca J, Rodriguez-Roisin R. Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation.

This article has been cited by other articles:

				H. A. Manrique, F. P. Gomez, P. A. Munoz, A. M. Pena, J. A. Barbera, J. Roca, and R. Rodriguez-Roisin Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses Eur. Respir. J., June 1, 2008; 31(6): 1205 - 1212. [Abstract] [Full Text] [PDF]

				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]

				J. Gabrijelcic, A. Casas, R.A. Rabinovich, J. Roca, J.A. Barbera, K.F. Chung, and R. Rodriguez-Roisin Formoterol protects against platelet-activating factor-induced effects in asthma Eur. Respir. J., January 1, 2004; 23(1): 71 - 75. [Abstract] [Full Text] [PDF]

				A.A. Acuna, J. Gabrijelcic, E.M. Uribe, R. Rabinovich, J. Roca, J.A. Barbera, K.F. Chung, and R. Rodriguez-Roisin Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma Eur. Respir. J., May 1, 2002; 19(5): 872 - 878. [Abstract] [Full Text] [PDF]

				A. L. ECHAZARRETA, B. DAHLEN, G. GARCIA, C. AGUSTI, J. A. BARBERA, J. ROCA, S.-E. DAHLEN, and R. RODRIGUEZ-ROISIN Pulmonary Gas Exchange and Sputum Cellular Responses to Inhaled Leukotriene D4 in Asthma Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 202 - 206. [Abstract] [Full Text] [PDF]

				N. R. HENIG, M. L. AITKEN, M. C. LIU, A. S. YU, and W. R. HENDERSON Jr. Effect of Recombinant Human Platelet-activating Factor-Acetylhydrolase on Allergen-induced Asthmatic Responses Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 523 - 527. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				R. M. MARRADES, J. ROCA, J. A. BARBERÁ, L. de JOVER, W. MACNEE, and R. RODRIGUEZ-ROISIN Nebulized Glutathione Induces Bronchoconstriction in Patients with Mild Asthma Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 425 - 430. [Abstract] [Full Text]

				F. P. GÓMEZ, R. IGLESIA, J. ROCA, J. A. BARBERÁ, K. FAN CHUNG, and R. RODRIGUEZ-ROISIN The Effects of 5-Lipoxygenase Inhibition by Zileuton on Platelet-activating-factor-induced Pulmonary Abnormalities in Mild Asthma Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 1559 - 1564. [Abstract] [Full Text]