Predictors of methacholine challenge testing results in subjects without airflow obstruction

Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEV₁ (PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry.

All patients who completed MCT at Montfort Hospital between January 1^st, 2016 and December 31^st, 2018 were identified. Subjects with a reduced FEV₁/FVC ratio were excluded. We used Pearson's chi-squared test and point-biserial correlation method to determine which variables had a significant relationship (p < 0.05) with MCT results.

23.3% of patients who underwent MCT had airflow limitation. In the 1126 subjects with a normal FEV₁/FVC ratio, PC20 ≤ 16 mg/mL was found in 13.0%. Younger age, female gender, body mass index ≥ 40, and reported wheezing were factors associated with increased probability of airway hyper responsiveness. Lower FEV₁, significant improvement of the FEV₁ post-bronchodilator, reduced FEF25%-75%, greater FEF25%-75% reversibility, airway resistance measurements above the upper limit of normal, and increased blood eosinophil counts were predictive of abnormal MCT.

Only 13.0% of patients referred for MCT had a PC20 ≤ 16 mg/mL when the FEV₁/FVC ratio was normal, highlighting the need to further define in which individuals this test is truly warranted. Further investigation is required to develop an easy-to-use and validated prediction model in order to better understand patients' pretest probability of abnormal MCT.