Leukotriene D4 and methacholine bronchial provocation tests for identifying leukotriene-responsiveness subtypes

Background: Both leukotriene D-4 (LTD4) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain unexplored. Objectives: We sought to compare the 2 tests and classify leukotriene-responsiveness subtypes in asthmatic patients. Methods: In this randomized cross-over study we enrolled healthy subjects and asthmatic patients with different control statuses. All subjects underwent both tests with a 2- to 14-day interval. Distribution and correlation of cumulative doses inducing a 20% decrease in FEV1, LTD4/methacholine potency ratio, diagnostic value, and adverse events were recorded and analyzed. Asthmatic patients with a lower cumulative dose for LTD4 and a higher leukotriene/methacholine potency ratio than geometric means were regarded as leukotriene responsive. Results: Twenty patients with uncontrolled, 22 with partly controlled, and 20 with controlled asthma and 21 healthy subjects were enrolled. Geometric means of cumulative doses for LTD4 and methacholine (0.272 nmol vs 0.945 mu mol) were lowest in patients with uncontrolled asthma, followed by those with partly controlled (0.387 nmol vs 1.933 mu mol) and controlled (1.484 nmol vs 3.946 mu mol) asthma. The average potency ratio was highest in those with partly controlled asthma (5000.2), followed by those with uncontrolled (3477.7) and controlled (2702.6) asthma. Eighteen leukotriene-responsive asthmatic patients (29.03%) with a cumulative dose of LTD4 of 0.533 nmol or less and a potency ratio of 3647 or greater were identified. Adverse events, including tachypnea and chest tightness, were similar and mild. No serious adverse event was reported. Conclusion: Diagnostic value and safety were ideal in both tests. The combination of cumulative dose for LTD4 and potency ratio might be useful to identify leukotriene-responsive asthmatic patients. (J Allergy Clin Immunol 2013;131:332-8.)