Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapnic dry air hyperventilation in patients with asthma.

Abstract

Background It has been suggested that inhaled corticosteroids may provide greater protection against constrictor stimuli that act indirectly such as exercise than those that act directly such as histamine. Methods The effects of six weeks treatment with inhaled budesonide (800 ug twice daily) on bronchial reactivity to histamine, exercise, and eucapnic voluntary hyperventilation of dry air were compared in a double blind, placebo controlled, non-crossover study in 40 subjects with asthma. Change in bronchial reactivity to histamine and eucapnic hyperventilation over the six weeks was measured as change in the provocative dose of histamine or dry air causing a 20% fall in FEV, (PD20 histamine and PV20 eucapnic hyperventilation (EVH) of dry air); this was not possible for exercise because of the development of refractoriness. To enable the change in response to all three stimuli to be compared, the response (percent fall in FEV,) to a fixed dose was measured for all three challenge tests. Results After budesonide there was an increase in PD20 histamine from 0-48 to 2-81 pmol and in PV20 EVH from 364 to 639 litres, and a significant correlation between the changes in PD20 histamine and PV20 EVH (r = 0-63). The median percentage fall in FEV, in response to eucapnic hyperventilation, exercise, and histamine was similar before budesonide (25-5%, 26-6%, and 24-5%); the reduction in the percentage fall in FEV, with budesonide was also similar for the three challenges (18-9%, 17-5%, and 16-6%), and all differed significantly from the changes following placebo. There was a significant correlation between change in percentage fall in FEV, after budesonide with the three stimuli (histamine v exercise: r = 0-48; histamine v eucapnic hyperventilation: r = 0-46; exercise v eucapnic hyperventilation: r = 0-63). Conclusion The similar magnitude of change in bronchial reactivity to all three stimuli after budesonide and the within subject correlation obtained between these changes suggest that corticosteroids act by a common mechanism to protect against eucapnic hyperventilation, exercise, and histamine.Patients with asthma show increased airway reactivity to a wide range of stimuli, some of which appear to act directly on airway smooth muscle and some indirectly through mast cell mediator release or sensory nerve stimulation. Drugs such as beta2 agonists reduce bronchial reactivity irrespective of the stimulus, whereas others, such as sodium cromoglycate and inhaled frusemide, reduce the airway response to challenges that act indirectly, such as exercise,' 2metabisulphite,3'4 and cold air hyperventilation,5 with little or no effect on directly acting stimuli such as histamine and methacholine.67Corticosteroids when given regularly have been shown to inhibit the response to most bronchoconstrictor stimuli,"'9 but whether they give similar protection against different forms of challenges is not clear. It has been suggested that they may have a greater effect on exercise induced bronchoconstriction than that induced by hist...

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