Effect of acute alterations in inspired oxygen tension on methacholine induced bronchoconstriction in patients with asthma

Abstract

Abstractmild to moderate patients with stable asthma. Background -Recent in vitro and in vivo studies in animals have suggested that am- (Thorax 1997;52:453-457) bient oxygen tension may influence airway Keywords: hyperoxia, hypoxia, bronchoconstriction, responsiveness to bronchoconstrictor methacholine, asthma. stimuli. These observations may have relevance to the management of acute exacerbations of asthma. The present studiesLittle is known about the effect of acute alterwere designed to examine the influence ations in oxygen tension on the responsiveness of inspired oxygen tension (Fi 2 1.0, 0.21, of the airways to bronchoconstrictor stimuli. 0.15) on methacholine induced broncho-Recent in vitro and in vivo studies in animals constriction in patients with asthma.suggest that hypoxia potentiates and hyperoxia Methods -In a dual study two groups of attenuates the airway constrictor response to asthmatic patients performed methacertain stimuli. 1 2 Similar in vivo studies in man, choline inhalation challenges breathing however, have produced conflicting findings. The present studies were designed to in-(dose of methacholine causing a 20% fall vestigate the effect of acute hypoxia and in forced expiratory volume in one second hyperoxia on methacholine induced broncho-(FEV 1 )) were calculated after each methaconstriction in patients with asthma. choline challenge by linear interpolation from the logarithmic dose response curve. Plasma catecholamine levels were measured before and after methacholine chal-Methods lenges as well as heart rate, oxygen  saturation, and percentage end tidal car-Study 1 Department of bon dioxide levels.Eleven mild asthmatic patients (five men) of Respiratory Medicine, West GlasgowResults -The geometric mean PC 20 value mean (SD) age 42 (12) years were recruited Hospitals University for methacholine was significantly lower into the study (table 1). All were receiving NHS Trust, Glasgow on the hypoxic study day than on the nor-inhaled 2 agonists as required, 10 were re- Fourteen adult mild asthmatic patients (five Returned to authors ml (95% CI 0.83 to 2.51)). men) of mean (SD) age 36 (9.2) years were 16 September 1996 Conclusions -Acute hypoxia potentiatesRevised version received recruited into the study (table 1). All were 7 January 1997 methacholine induced bronchoconstric-taking inhaled 2 agonists on an as required Accepted for publication tion and acute hyperoxia has no effect in 9 January 1997 basis, 10 were receiving regular inhaled corticosteroids, two were taking regular oral theophyllines, and one inhaled salmeterol. In both studies on each study day inhaled 2 as usual. They were asked to refrain from caffeine containing products for eight hours FEV 1 =forced expiratory volume in one second; PC 20 methacholine=concentration of methacholine provoking a fall in FEV

Lung disease at high altitude

“…The data regarding the effect of hypoxia on airway reactivity are conflicting, as studies report either an increase [145,146], decrease [147] or no change [148,149] in bronchial responsiveness to a methacholine challenge.…”

Travel to high altitude with pre-existing lung disease

“…Several studies demonstrate that hypoxia increases bronchial responsiveness to methacholine [116,117], while other studies, using comparable degrees of hypoxic exposure, have shown no change in either the response to methacholine [118,119] or specific airway resistance [120]. In addition to these effects on bronchial hyperresponsiveness, acute isocapnic hypoxia has also been shown to reduce methacholine-induced symptoms of dyspnoea and chest tightness [121], a result which suggests that asthmatic patients may not perceive when they are developing worsening symptoms at high altitude.…”

Effect of chronic hypoxia on calcium signalling in airway smooth muscle cells

“…Both acute and chronic hypoxia alter smooth muscle contractility [1–3]. In airways, acute hypoxia appears to increase responsiveness both in vitro [4] and in vivo [5–9]. Surprisingly, the effect of chronic hypoxia on airway smooth muscle is poorly understood, although chronic hypoxia is frequently observed in patients with chronic obstructive pulmonary disease [10] and may play a role in the bronchial hyperresponsiveness associated with this disease [11].…”