A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study

Backgrounds: Asthma is a chronic inflammatory disorder in the airways, which subsequently leads characteristic airway hyperresponsivenss (AHR). Measuring or proving the existence of AHR is the mainstay in its diagnosis. In Korea, airway provocation test with methacholine (direct test) had been used in clinical practices until the recent official objection of KFDA. Instead, airway provocation test with mannitol is used (indirect test), which shows lower sensitivity and consumes longer test-time compared with those in methacholine, despite higher specificity in the diagnosis of asthma. To overcome its demerits, a sequential indirect-direct provocation test was designed.

Methods: A prospective observational study was conducted in asthma-suspicious subjects. Indirect test was performed with skipped doses but up to 640 mg in accumulation. Methacholine inhalation (8mg/mL) by 2-min tidal breathing method was applied thereafter in the subjects who showed negative (PD15 > 640 mg of mannitol). Regardless of the results, at the end of the tests, bronchodilator was applied. AHR positive were defined as either PD15 < 640 mg of mannitol, PC20 < 8mg/mL of methacholine, or 20% increment of FEV1 in bronchodilator.

Results: Twenty four asthma-suspicious subjects (median age of 54, 11 males, 45.8%) were enrolled. The test-time test was theoretically shortened at least 10 min compared with that of suggested indirect test. In AHR, two subjects (8.3%) showed positive in mannitol provocation. Five (20.8%) showed positive in methacholine provocation compared with baseline FEV1 and 2 (8.3%) compared with FEV1 after 640mg of mannitol. Four (16.7%) showed positive in bronchodilator. Overall, 5 subjects (22.7%) showed AHR positive among 22 negatives in indirect test. No adverse reaction except for coughing during inhalation of mannitol was identified.

Conclusions: The sequential indirect-direct provocation facilitates to detect AHR in higher sensitivity and shorter test-time. As a confirmative test of asthma in clinical practice, it can be applied effectively after modification and verification.