EFFECT OF ACUTE ALTERATIONS IN INSPIRED OXYGEN-TENSION ON METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN PATIENTS WITH ASTHMA

Background - Recent in vitro and in vivo studies in animals have sugge sted that ambient oxygen tension may influence airway responsiveness t o bronchoconstrictor stimuli. These observations may have relevance to the management of acute exacerbations of asthma. The present studies were designed to examine the influence of inspired oxygen tension (Fio (2) 1.0, 0.21, 0.15) on methacholine induced bronchoconstriction in pa tients with asthma. Methods - In a dual study two groups of asthmatic patients performed methacholine. inhalation challenges breathing eithe r air (Fio(2) 0.21) or a hypoxic gas mixture (Fio(2) 0.15) in study 1 and air (Fio(2) 0.21) or hyperoxia (Fio(2) 1.0) in study 2. The gases were administered through a closed breathing circuit in a randomised d ouble blind fashion. The PC20 values (dose of methacholine causing a 2 0% fall in forced expiratory volume in one second (FEV1)) were calcula ted after each methacholine challenge by linear interpolation from the logarithmic dose response curve. Plasma catecholamine levels were mea sured before and after methacholine challenges as well as heart rate, oxygen saturation, and percentage end tidal carbon dioxide levels. Res ults - The geometric mean PC20 value for methacholine was significantl y lower on the hypoxic study day than on the normoxic day in study 1 ( mean difference in PC20 values 2.88 mg/ml (95% CI 1.4 to 5.3); p < 0.0 5), but there was no significant difference in the geometric mean PC20 value for methacholine between the hyperoxic and normoxic study days in study 2 (mean difference in PC20 values 1.45 mg/ml (95% CI 0.83 to 2.51)). Conclusions - Acute hypoxia potentiates methacholine induced b ronchoconstriction and acute hyperoxia has no effect in mild to modera te patients with stable asthma.