Clinical utility of ultrahigh fractional exhaled nitric oxide in predicting bronchial hyperresponsiveness in patients with suspected asthma

Background Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker for airway eosinophilic inflammation. However, the clinical value of ultrahigh FeNO (>= 100 parts per billion (ppb)) in predicting asthma is never explored. We aimed to investigate the value of ultrahigh FeNO as a predictor of bronchial hyperresponsiveness (BHR), an important index for asthma diagnosis. Methods A retrospective cohort study was conducted on 259 patients with suspected asthma who received the examination of FeNO, spirometry, bronchial provocation test (BPT) and differential cell count of induced sputum. Patients were stratified by FeNO value: ultrahigh (group A:>= 100 ppb), high (group B: 50-99 ppb), intermediate (group C: 26-49 ppb) and normal (group D:<= 25 ppb). The positive rates of BPT and sputum eosinophils percentage (Eos%) were compared among four cohorts. The correlations between FeNO and sputum Eos% were measured. Results A significant higher positive rate of BPT was observed in group A (90.91%) than all others (B: 51.43%, C: 31.43%, D: 28.13%, all p<0.01). Referring to group D, the ORs of positive BPT in groups A, B and C were 26.84, 2.84 and 1.05. Sputum Eos% in group A (19.75 (7.00, 46.25)) is higher than that in others (B: 3.50 (1.00, 12.75), C: 1.13 (0.06,3.50), D: 0.50 (0.00, 2.13)). FeNO correlates with sputum Eos% in groups A and B, but not group C or D. Conclusions Ultrahigh FeNO correlates with BHR and could serve as a practical alternative to methacholine challenge to support an asthma diagnosis in patients with suspected asthma in primary care.