BACKGROUND: As fractional exhaled nitric oxide (FeNO) has been evaluated only in certain settings for asthma diagnosis, we investigated whether FeNO values could predict positive methacholine challenge testing (expressed as PD20) in subjects with suspected asthma but without spirometric reversibility.METHODS: Subjects with asthma-like symptoms and negative bronchodilation test were initially evaluated to undergo FeNO measurement and methacholine bronchial challenge. Diagnostic performance of FeNO to predict PD20 to methacholine <800 μg was examined by constructing receiver-operating characteristic curves.RESULTS: A total of 112 subjects met the inclusion criteria. In all subjects, FeNO >32 ppb was associated with a sensitivity of 0.47 and a specificity of 0.85 for the identification of the PD20 <800 μg (AUC = 0.691, 95% CI = 0.6-0.775, p = 0.00002). In smokers, FeNO >11 ppb was associated with a sensitivity of 0.85 and a specificity of 0.5 for the identification of PD20 <800 μg (AUC = 0.625, 95% CI = 0.45-0.772, p = 0.18), while in atopics a FeNO level >26 ppb was associated with a sensitivity of 0.55 and a specificity of 0.85 (AUC = 0.677, 95% CI = 0.53-0.8, p = 0.02).CONCLUSIONS: In subjects with symptoms compatible with asthma but without spirometric reversibility, specific cutoff levels for FeNO levels significantly predict the positive methacholine challenge, with significant confounding factors being atopy and current smoking.