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-PD(15) and MCh-PC(20) 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-PD(15) and MCh-PC(20) and only 52.9% of patients with MCh-PC(20)≤4 mg/mL showed HS-AHR, but 4 patients with HS-AHR showed MCh-PC(20)>4 mg/mL. There were significant correlations between both HS-PD(15) and MCh-PC(20) and FEV(1), or sputum eosinophils, but FEV(1) was more closely related to MCh-PC(20) (r=0.478, p<0.01) than to HS-PD(15) (r=0.278, p<0.05), and sputum eosinophils were more closely related to HS-PD(15) (r=−0.324, p<0.01) than to MCh-PC(20) (r=−0.317, p<0.05). Moreover, the IL-5 level (r=−0.285, p<0.05) and IFN-γ/IL-5 ratio (r=0.293, p<0.05) in sputum were significantly related to HS-PD(15), but not to MCh-PC(20). CONCLUSION : HS-AHR may reflect allergic asthmatic airway inflammation more closely than MCh-AHR.