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.