Sensitivity and Validity of Three Bronchial Provocation Tests To Demonstrate the Effect of Inhaled Corticosteroids in Asthma. Part 8

Posted on October 24th, 2020 by admin

In addition, one study has showed bradykinin to be more sensitive than methacholine, and another study in children showed cold air to be more sensitive than methacholine. The studies that have not shown any difference between indirect and direct challenges in demonstrating the effects of ICS have included the following indirect stimuli: brady-kinin, dry air hyperventilation, exercise, and hyperosmolar saline solution. Our study adds mannitol and cold air to that list. In fact, dry air hyperventilation was less sensitive than histamine challenge in one study, corresponding with our finding that cold air hyperventilation was less sensitive than histamine. In conclusion, these findings suggest that a special sensitivity to demonstrate ICS-induced changes in bronchial responsiveness is not a feature of all indirect challenges as a group, but is restricted to adenosine and possibly to some other challenges.

The poor sensitivity of cold air challenge to demonstrate ICS-induced changes in bronchial responsiveness is probably due to the mild responses to cold air at baseline. Only 7 of 17 patients who were both mannitol and histamine responsive demonstrated > 9% falls in FEV1 after cold air challenge. This finding is in accordance with our previous study pointing to a low sensitivity of cold air also in the diagnostic of adult asthma. As a consequence of small baseline responses, the ICS-induced changes in the cold air responses could also not be large; however, in a study by Nielsen and Bisgaard, cold air was more sensitive than methacholine to demonstrate the effect of budesonide in 2- to 5-year-old asthmatic children; they used very similar equipment and protocol to those in the present study. This finding is in agreement with our previous results that the responsiveness to cold air increases with younger age. In conclusion, cold air is probably a sensitive tool to demonstrate the effect of ICS in pediatric asthma, but not in adult asthma.

To the best of our knowledge, the present study is the first to compare the validity of different types of bronchial provocation tests in monitoring the effect of ICS in asthma. Validity in this study represents convergence validity, ie, the relationship of the instrument to other instruments that measure the same thing. Our results suggest that the convergence validity of the indirect challenges, mannitol and cold air, to demonstrate the healing of asthma by ICS may be higher than that of histamine, a direct challenge. Change in responsiveness to these indirect challenges, but not to histamine, correlated significantly with the change in symptom severity. Leuppi showed that in stable asthmatic patients with ICS treatment, hyperresponsiveness to mannitol predicts asthma exacerbation during ICS dose tapering better than does hyperresponsiveness to histamine challenge.

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