Background: Many patients with mild asthma are undiagnosed and untreated for low diagnostic sensitivity of the bronchodilation test (BDT). Objective: Investigating whether airway reversibility in BDT alone or together with fractional exhaled nitric oxide (FENO) can predict the response to anti-asthma therapy (RAT) in suspected asthma patients. Methods: This study included patients with chronic recurrent asthma symptoms, normal forced expiratory volume in 1 second (FEV1), and negative BDT. Inhaled corticosteroid (ICS) and long-acting β agonist (LABA) were given for 4 weeks. Positive RAT (PRAT) was defined as improved symptoms and increase of FEV1 > 200 mL after ICS/LABA. Lung tissues from 19 patients with lung nodules, grouped by predicted RAT, were also analyzed. Results: Of 102 patients, the PRAT group had higher FENO and greater absolute (∆) and (∆%) percent improvements of forced vital capacity, FEV1, and forced expiratory flows (FEFs) in BDT than the negative RAT group. The AUCs of FENO, ∆FEV1%, ∆FEF25-75%, and ∆FEF75% for PRAT were 0.703, 0.824, 0.736, and 0.710, with the optimal cut-off values of 33 ppb, 3.50%, 15.26%, and 26.04%. A joint model of FENO and ∆FEV1% increased the AUC to 0.880. IL-4, IL-5, IL-13, and NFκB were higher in lung tissues of patients with predicted PRAT than with predicted NRAT. Conclusion: ∆FEV1% > 3.50% in BDT together with FENO > 33 ppb predicted PRAT and an asthma diagnosis in patients with normal FEV1 and negative BDT. Evidence of pathological changes in the early stage of asthma increased the credibility of the predictive model.

Background: 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. 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 BHR (n=522), subjects positive for BHR (n=170) showed increased FENO values, 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 BHR+ patients (61.17%), and 132 BHR- patients (25.29%) (P<.001). The areas under the curve (AUCs) of variables used singly for a BHR diagnosis were lower than 0.77. Using joint models of FEF50%, FEF75%, or FEF25%-75% with FENO increased the AUCs to 0.845, 0.824, and 0.844, respectively, significantly higher than univariate AUCs (P <.001 for all). Patients who reported chest tightness (n=75) had lower FEFs than patients who did not (P<.001 for all). In subjects with chest tightness, the combination of FEF50% or FEF25%-75% with EOS also increased the AUCs substantially, to 0.815 and 0.816, respectively (P <.001 for all versus the univariate AUCs). Conclusion: FENO combined with FEF50% and FEF25%-75% predict BHR in patients with normal FEV1. FEF25%-75%. FEF50%, or FEF25%-75% together with EOS also can potentially suggest asthma in patients with chest tightness.