Lack of Significant Bronchial Reactivity to Inhaled Normal Saline in Subjects with a Positive Methacholine Challenge Test

Abstract

Patients with symptoms suggestive of asthma often have normal resting pulmonary function. In these patients, a determination of airway responsiveness by bronchial challenge is useful in demonstrating bronchial hyperreactivity (BHR), a defining feature of asthma. In the methacholine (Mch) challenge, it is recommended that following a baseline measurement of FEV₁, the patient inhale the normal saline (NS) diluent and FEV₁ be repeated to assess for nonspecific BHR to NS. It is also recommended that post-NS inhalation FEV₁ should be used as the control value from which decrement in FEV₁ is compared following Mch challenge. Mch testing was performed in 44 patients with symptoms suggestive of asthma (cough, chest tightness, dyspnea) and normal resting pulmonary function. Baseline spirometry was obtained and repeated after inhalation of NS and after five breaths each of Mch at the following concentrations: 0.025 mg/ml, 0.25 mg/ml, 2.5 mg/ml, 10 mg/ml, and 25 mg/ml. The procedure was terminated when FEV₁ decreased to at least 80% of the post-NS value or if the maximal concentration of Mch had been reached. The post-NS FEV₁ was ≥91% of the pre-NS value in all the subjects (range 91-105%). Using the post-NS FEV₁ as the recommended control value, 20 patients (45%) had a positive Mch challenge and 24 patients (55%) had a negative Mch challenge. Had we used the pre-NS FEV₁ as a control value, only 2 patients would have been reclassified, and when these 2 cases are carefully examined, there would have been no significant change in the clinical interpretation of the MCh test. We conclude that patients with a significant BHR to Mch do not have a significant BHR to NS. However, since the NS control has been accepted as part of the standardized Mch challenge, it should be included in all research studies and in most clinical Mch challenges.