Effect of lowering methacholine challenge test cutoff in children

Background: The diagnosis of asthma is based on clinical judgment, history of personal or familial atopy, and testing, typically with a methacholine challenge test (MCT). Guidelines suggest a provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) cutoff of 4 mg/mL for a positive test result.

Objective: To investigate the effect of lowering the MCT PC20 cutoff from 8 to 4 mg/mL on the number of positive test results and the distribution of test results.

Methods: A retrospective study was conducted at the Montreal Children's Hospital from January 1, 2006, through June 31, 2012, on patients referred by nonrespiratory physicians. A 2-minute tidal breathing dosing protocol was used, and the PC20 was calculated by linear interpolation.

Results: A total of 748 patients were tested using spirometry. A total of 134 (17.9%) had a negative MCT result, and 614 (81.1%) responded at 8 mg/mL or less. A total of 570 patients (92.8% of respondents) responded at a dose of 4 mg/mL or higher (median PC20 of 0.47 mg/mL), with the remainder (7.2% of respondents) responding at a dose between 4 and 8 mg/mL (median PC20 of 6.37 mg/mL). There was no difference in the number of positive test results between the sexes, regardless of cutoff. The sensitivity of MCT was 82.1% at a cutoff of 8 mg/mL and 76.2% at 4 mg/mL. With a pretest likelihood of asthma of 75%, the specificity was 71.2%.

Conclusion: In a standard pediatric referral population, using a PC20 cutoff of 4 mg/mL provided a sensitivity of 76.2%, and only excluded 5.8% of all those referred for suspicion of asthma (7.2% of all test results were ≤8 mg/mL). This finding suggests that a PC20 of 4 mg/mL can reasonably be used as a cutoff for a positive MCT result in children.