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

Abstract

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 (≥25 ppb) and high FeNO (≥40 ppb and ≥ 50 ppb)—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 ≥25 ppb, ≥40 ppb, and ≥ 50 ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25 ppb was 55%, which decreased to 37% and 27% at ≥40 ppb and ≥ 50 ppb, respectively. The specificity of FeNO ≥25 ppb, ≥40 ppb, and ≥ 50 ppb was 66%, 86%, and 89%, respectively. The ROC‐AUC for FeNO was 0.656. Conclusions FeNO ≥40 ppb provides good specificity, that is, the ability to rule‐in 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.

Exhaled and Systemic Biomarkers to Aid the Diagnosis of Bronchial Asthma in Elite Water Sports Athletes

“…The ERS recommends a cutoff of >50 ppb for a specificity of >90% or a cutoff of >40 ppb for the best compromise between sensitivity and specificity. In support of this, Dickinson et al (16) have reported a study involving recreational and elite athletes from a wide range of athletic disciplines, that F ENO ≥ 40 ppb predicts EIB with the best specificity/sensitivity ratio (86% and 37%, respectively). However, given the low sensitivity, the authors recommend against using F ENO alone in diagnosing EIB.…”

“…Elevated fractional exhaled nitric oxide (F ENO ) is a marker of airway eosinophilic inflammation and a recommended diagnostic tool for bronchial asthma in the normal population (14,15). However, F ENO levels in athletes may be different than of the general population, as highlighted by a recent study where 45% of the participants with EIB had values <25 ppb (16).…”

Exercise-Induced Asthma: Managing Respiratory Issues in Athletes

“…A recent multi-center retrospective analysis involving 488 athletes has shown that an FeNO level of ≥40 ppb offers good specificity, allowing it to be useful in confirming a diagnosis of EIB. However, given its limitations in sensitivity and predictive values, FeNO should not be used as a substitute for indirect bronchial provocation testing in athletes [ 45 ].…”