The value of small airway function parameters and fractional exhaled nitric oxide for predicting positive methacholine challenge test in asthmatics of different ages with FEV(1) ≥ 80% predicted

BACKGROUND: Small airway function parameters (SAFPs) combined with fractional exhaled nitric oxide (FeNO) can predict a positive methacholine challenge test (MCT) for asthma diagnosis. However, their predictive utility in patients with forced expiratory volume in one second (FEV(1)) ≥80% predicted within different age ranges remains unclear. This study aimed to assess the utility of SAFPs, alone or combined with FeNO, to predict a positive MCT in patients in two age groups (<55 and ≥55 years) with asthma‐suggestive symptoms and FEV(1) ≥80% predicted. METHODS: We enrolled 846 Chinese patients with suspected asthma and standard spirometry, FeNO, and MCT findings. Using the area under the curves (AUCs), the utility of SAFPs, alone or combined with FeNO, for predicting a positive MCT was analyzed in a discovery (n = 534) and validation cohort (n = 312) in both age groups with FEV(1) ≥80% predicted. RESULTS: In the discovery cohort, the optimal cut‐off values for predicting a positive MCT in patients aged <55 years (74.2% and 74.9% for forced expiratory flow (FEF)(50%) and FEF(25%–75%), respectively) were higher than those in patients aged ≥55 years (65.0% and 62.9% for FEF(50%), FEF(25%–75%), respectively). However, the optimal FeNO value in patients aged <55 years (43 ppb) was lower than that in patients aged ≥55 years (48 ppb). FeNO combined with SAFPs (FEF(50%), FEF(25%–75%)) significantly increased the AUCs in both groups (≥55 years [0.851 for FEF(50%) and 0.844 for FEF(25%–75%)]; <55 years [0.865 for FEF(50%) and 0.883 for FEF(25%–75%)]) compared with a single parameter (p < 0.05). These findings were confirmed in the validation cohort. Compared with patients ≥55 years, those aged <55 years had higher and lower optimal cut‐off values for SAFPs and FeNO, respectively. The AUCs of FeNO combined with SAFPs for predicting a positive MCT for asthma diagnosis were significantly higher than those of the individual parameters (p < 0.05) in both age groups. CONCLUSIONS: There were age‐group differences in the utility of SAFPs combined with FeNO for predicting a positive MCT. Patients with an asthma‐suggestive history and a normal FEV(1) should be stratified by age when using SAFPs combined with FeNO to predict a positive MCT.