Bronchodilator Response After Negative Methacholine Challenge Test Predicts Future Diagnosis of Asthma

Abstract

Background. 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. Methods. Over a 5 –year period, starting from January 2004, the change in the forced expiratory volume in 1 second (FEV₁) 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 FEV₁ of more than 200 ml and 12%) were questioned for the presence of asthma on January 2009. Results. Overall 645 subjects (mean age 21.4 ± 2.3 years) underwent MCT. Negative MCT (defined as PC₂₀ > 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 FEV₁ by 20% predicted asthma with sensitivity, specificity, and positive predictive values of 86.9%, 66.6%, 83.3%, respectively, p = 0.0022. Conclusions. 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.

Keywords:

• asthma
• methacholine
• airway hyperresponsiveness