Methods: A double-blind randomised controlled trial in undiagnosed patients, aged 18-80, with cough, wheeze and/or dyspnoea and <20% bronchodilator reversibility, 4-week treatment period with ICS (QVAR 80 mcg, two puffs twice per day, equivalent to 400 mcg beclomethasone dipropionate) or placebo. Stratified randomisation was carried out within categories of baseline FeNO – normal (≤25 ppb), intermediate (>25 - <40 ppb), and high (≥40 ppb) - allocation. Generalised linear modelling assessed FeNO as a predictor of response, estimating an interaction effect between FeNO and treatment, on change in ACQ7. Logistic regression assessed FeNO and clinical opinion of asthma status as predictors of response.
Findings: 294 patients were randomised (148 ICS, 146 placebo). Following exclusions due to protocol violations 214 patients were analysed (114 ICS, 100 placebo). Treatment effects were significant for high FeNO (mean change in ACQ7, 0.49 [95% CI, 0.14, 0.84]), non-significant for normal and intermediate FeNO (0.10 [95% CI, -0.24, 0.44] and 0.25 [-0.10, 0.61]: P=0.044 for interaction). FeNO > 50 ppb was associated with greater odds of improvement in cough on the visual analogue scale (odds ratio, 2.37 [1.01, 5.55]), while an affirmative clinical opinion of asthma was not predictive (0.92 [0.47,1.82]). This study is registered on ClinicalTrials.gov (number: NCT02294279).Interpretation: FeNO may predict response to ICS in patients with NSRS, while clinical opinion is not predictive.