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Pulmonary gas exchange responses to histamine and methacholine challenges in mild asthma

Servei de Pneumologia i Al.lèrgia Respiratòria, Dept de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

CORRESPONDENCE: R. Rodriguez-Roisin, Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clínic, Villarroel 170, Barcelona, Spain, 08036. Fax: 34 932275404

Keywords: airflow obstruction, bronchial challenge, mediators of inflammation, multiple inert gas elimination technique, ventilation-perfusion mismatch

Received: July 12, 2000
Accepted December 20, 2000

This study was supported by grants 99/0135 from the Fondo de Investigación Sanitaria (FIS), 1997 SGR00086 from the Comissionat per a Universitats i Recerca de la Generalitat de Catalunya, and by AstraZeneca. A.L. Echazarreta (1997) and F.P. Gómez (1996) were Research Fellows from the European Respiratory Society (ERS), J. Ribas was Research Fellow from the Comissió Interdepartamental de Recerca i Innovació Tecnológica (CIRIT) (1997), and E. Sala was awarded by a Hospital Clínic Research Fellowship (1997).

Histamine (HIST) produces greater changes in bronchial and pulmonary vasculature, and so may produce more gas exchange abnormalities, than methacholine (MTH) after inhalational challenge. The goals of this study were to compare the effects of HIST and MTH challenge on pulmonary gas exchange in patients with mild asthma at an equivalent degree of bronchoconstriction.

Eleven patients were studied (mean±sem age, 22±1 yr; forced expiratory volume in one second (FEV₁), 91±5% pred) using a randomized, double-blind cross-over design. Respiratory system resistance (R_rs), arterial blood gases, and ventilation-perfusion distributions were measured before and after HIST/MTH challenges when cumulative doses caused a 30% fall in FEV₁.

Compared with baseline, HIST and MTH provoked similar moderate to severe increases in R_rs (p<0.005 each), and mild to moderate decreases in arterial oxygen tension (P_a,O2) due to ventilation-perfusion abnormalities (dispersion of pulmonary blood flow -log SDQ-, 0.40±0.03–0.71±0.08 and 0.47±0.04–0.89±0.06; normal values <0.60–0.65), respectively, similar to those shown in mild to moderate acute asthma, without differences between them.

For the same degree of airflow obstruction, both histamine and methacholine bronchoprovocations induce, in patients with mild asthma, very similar disturbances in ventilation-perfusion distribution and respiratory system resistance, suggesting similar mechanisms of airway narrowing.

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