Fractional exhaled nitric oxide in the assessment of exercise- induced bronchoconstriction: A multicenter retrospective analysis of UK- based athletes

Introduction: Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes.

Method: Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds—that is, intermediate (≥25ppb) and high FeNO (≥40ppb and≥50ppb)—and were evaluated against objective evidence of EIB (≥10% fall in FEV1). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC).

Results: Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25ppb, ≥40ppb, and≥50ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25ppb was

55%, which decreased to 37% and 27% at ≥40ppb and≥50ppb, respectively. The specificity of FeNO ≥25ppb, ≥40ppb, and≥50ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656.

Conclusions: FeNO ≥40ppb provides good specificity, that is, the ability to rulein a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes.