Purpose: Patients with variable symptoms suggestive of asthma but with normal forced expiratory volume in 1 second (FEV₁) 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 FEV₁≥ 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 FEV₁, FEV₁/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 FEV₁. FEF_25%-75%, FEF_50%, or FEF_25%-75% together with EOS also can potentially suggest asthma in patients with chest tightness.
Keywords: asthma diagnosis, small-airway function, fractional exhaled nitric oxide, bronchial provocation, impulse oscillometry