Small-Airway Function Variables in Spirometry, Fractional Exhaled Nitric Oxide, and Circulating Eosinophils Predicted Airway Hyperresponsiveness in Patients with Mild Asthma

Purpose: Patients with variable symptoms suggestive of asthma but with normal forced expiratory volume in 1 second (FEV 1 ) often fail to be diagnosed without a bronchial provocation test, but the test is expensive, time-consuming, risky, and not readily available in all clinical settings. Patients and Methods: A cross-sectional study was performed in 692 patients with FEV 1 ≥ 80% predicted; normal neutrophils and chest high-resolution computed tomography; and recurrent dyspnea, cough, wheeze, and chest tightness. Results: Compared with subjects negative for AHR (n=522), subjects positive for AHR (n=170) showed increased FENO values, peripheral eosinophils (EOS), and R5-R20; decreased FEV 1 , FEV 1 /Forced vital capacity (FVC), and forced expiratory flow (FEFs) ( P ≤ .001 for all). Small-airway dysfunction was identified in 104 AHR + patients (61.17%), and 132 AHR − patients (25.29%) ( P < 0.001). The areas under the curve (AUCs) of variables used singly for an AHR diagnosis were lower than 0.77. Using joint models of FEF 50% , FEF 75% , or FEF 25%-75% with FENO increased the AUCs to 0.845, 0.824, and 0.844, respectively, significantly higher than univariate AUCs ( P < 0.001 for all). Patients who reported chest tightness (n=75) had lower FEFs than patients who did not ( P < 0.001 for all). In subjects with chest tightness, the combination of FEF 50% or FEF 25%-75% with EOS also increased the AUCs substantially, to 0.815 and 0.816, respectively ( P < 0.001 for all versus the univariate AUCs). Conclusion: FENO combined with FEF 50% and FEF 25%-75% predict AHR in patients with normal FEV 1 . FEF 25%-75% , FEF 50% , or FEF 25%-75% together with EOS also can potentially suggest asthma in patients with chest tightness.