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 (FEV1 ) ≥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 FEV1 ≥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 FEV1 ≥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 FEF25%-75% , respectively) were higher than those in patients aged ≥55 years (65.0% and 62.9% for FEF50% , FEF25%-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 (FEF50% , FEF25%-75% ) significantly increased the AUCs in both groups (≥55 years [0.851 for FEF50% and 0.844 for FEF25%-75% ]; <55 years [0.865 for FEF50% and 0.883 for FEF25%-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 FEV1 should be stratified by age when using SAFPs combined with FeNO to predict a positive MCT.
Keywords: age; asthma; fractional exhaled nitric oxide; methacholine challenge test; small airway; 关键词: 年龄, 哮喘, 呼出气一氧化氮, 乙酰胆碱激发试验, 小气道.
© 2021 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.