Asthmatic Airway Inflammation is More Closely Related to Airway Hyperresponsiveness to Hypertonic Saline than to Methacholine

BACKGROUND Airway hyperresponsiveness (AHR) to direct stimuli, such as methacholine (MCh), is observed not only in asthma but other diseases. AHR to indirect stimuli is suggested to be more specific for asthma. The purpose of this study was to determine whether asthmatic airway inflammation is more closely related to AHR to hypertonic saline (HS), an indirect stimulus, than to MCh. METHODS Sixty-four consecutive adult patients with suspected asthma (45 asthma and 19 non-asthma) performed a combined bronchial challenge and sputum induction with 4.5% saline, and MCh challenge on the next day. RESULTS Both HS-PD15 and MCh-PC20 were significantly lower in asthma patients than in non-asthma patients. However, the sensitivity/specificity for asthma was 48.9%/100%, respectively, in the HS test and 82.2%/84.2%, respectively, in the MCh test. There was a significant relationship between HS-PD15 and MCh-PC20 and only 52.9% of patients with MCh-PC20 < or = 4 mg/mL showed HS-AHR, but 4 patients with HS-AHR showed MCh-PC20 > 4 mg/mL. There were significant correlations between both HS-PD15 and MCh-PC20 and FEV1, or sputum eosinophils, but FEV1 was more closely related to MCh-PC20 (r = 0.478, p < 0.01) than to HS-PD15 (r = 0.278, p < 0.05), and sputum eosinophils were more closely related to HS-PD15 (r = -0.324, p < 0.01) than to MCh-PC20 (r = -0.317, p < 0.05). Moreover, the IL-5 level (r = 0.285, p < 0.05) and IFN-gamma/IL-5 ratio (r = 0.293, p < 0.05) in sputum were significantly related to HS-PD15, but not to MCh-PC20. CONCLUSION HS-AHR may reflect allergic asthmatic airway inflammation more closely than MCh-AHR.