Bronchodilator response after negative methacholine challenge test predicts future diagnosis of asthma

Currently there are no reliable means to predict the likelihood of a subject with negative results from a methacholine challenge test (MCT) to be diagnosed with asthma in the future. We sought to determine whether the magnitude of the response to bronchodilator (BD) administered after a negative MCT has a predictive value for future asthma.

Over a 5 -year period, starting from January 2004, the change in the forced expiratory volume in 1 second (FEV(1)) after inhaling BD (salbutamol) was recorded among subjects with negative MCT despite symptoms suggestive of asthma such as wheezing and dyspnea. Subjects with a significant response to BD (defined as improvement in FEV(1) of more than 200 ml and 12%) were questioned for the presence of asthma on January 2009.

Overall 645 subjects (mean age 21.4 +/- 2.3 years) underwent MCT. Negative MCT (defined as PC(20) > 16 mg/mL) was noted in 482 (74.7%) patients of whom significant response to BD was identified in 35. Over a median observation time of 2.1 years, 11 of them (31.4% of the study population and 1.7% of the entire cohort) were subsequently diagnosed with asthma. Improvement of FEV(1) by 20% predicted asthma with sensitivity, specificity, and positive predictive values of 86.9%, 66.6%, 83.3%, respectively, p = 0.0022.

Our findings suggest that administration of BD after a negative MCT enhances the diagnostic accuracy of the challenge test as it identifies subjects who are likely to develop clinical asthma in the future.