Pillai, S. M.

Abstract Rationale Exertional dyspnea in children presents a complex diagnostic challenge, often requiring multiple evaluations to uncover underlying etiologies. Exercise testing is the standard for diagnosing exercise-induced bronchoconstriction (EIB) in children but requires significant resources. Fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, has been proposed as an easier alternative to predict the need for exercise testing. The aim of this study is to evaluate the diagnostic utility of fractional exhaled nitric oxide (FeNO) as a non-invasive marker of bronchial hyperreactivity in pediatric patients with exertional dyspnea, by assessing its sensitivity, specificity, and predictive values in comparison to cardiopulmonary exercise testing (CPET), the gold standard for diagnosing exercise-induced bronchoconstriction (EIB). This study seeks to determine whether FeNO can reliably guide the need for CPET, potentially streamlining the diagnostic process in children with suspected EIB, while also identifying any limitations of FeNO as a standalone diagnostic tool. Methods In this retrospective study, we reviewed pediatric patients up to 18 years of age who presented with unexplained dyspnea and underwent both CPET and FeNO testing from July 2020 to February 2023. A post-exercise decline in FEV1% of ≥10% during CPET defined a positive result for EIB. For FeNO, a threshold of ≥25 parts per billion (ppb) was considered indicative of bronchial hyperreactivity. Diagnostic agreement between FeNO and CPET was analyzed using a 2x2 table, with CPET as the reference standard. Results Among 98 patients who completed CPET, the cohort had a mean age of 14 years (SD ± 2.42), mean BMI of 22.2 kg/m² (SD ± 5.25), and 71% were female. Of these, 40 patients also underwent FeNO testing. Compared to CPET, FeNO exhibited a sensitivity of 100%, a specificity of 2.6%, a positive predictive value of 5.1%, and a negative predictive value of 100% for identifying bronchial hyperreactivity in this setting. Conclusion FeNO testing shows high sensitivity but limited specificity for detecting bronchial hyperreactivity, effectively ruling out but not confirming it independently of CPET. These findings reinforce the essential role of CPET in diagnosing EIB and suggest that FeNO may serve best as an adjunctive tool, rather than a primary diagnostic measure, in evaluating children with exertional dyspnea. A limitation of this study is the reliance on a single FeNO threshold, which may not account for individual variability in bronchial inflammation responses.

Abstract Rationale Exertional dyspnea in children often necessitates a thorough evaluation to determine potential causes, with bronchial hyperresponsiveness (BHR) and exercise-induced bronchoconstriction (EIB) being among the most common. Cardiopulmonary exercise testing (CPET) is widely recognized as the gold standard for diagnosing EIB; however, it requires significant patient cooperation and specialized resources. The methacholine challenge test (MCT), a bronchial provocation test, is commonly employed to evaluate baseline airway hyperreactivity. Nonetheless, its reliability in predicting EIB in pediatric patients experiencing exertional dyspnea has not been well established. This study aims to evaluate the diagnostic accuracy of MCT compared to CPET in detecting BHR among pediatric patients with unexplained dyspnea. This assessment will help determine the potential of MCT as a complementary diagnostic tool for EIB. Methods We conducted a retrospective cohort study involving pediatric patients (up to 18 years of age) who underwent both CPET and MCT as part of their clinical evaluation for exertional dyspnea from July 2020 to February 2023. A reduction of ≥20% in FEV1% was considered a positive result for the methacholine challenge. In the CPET, a decrease of ≥10% in FEV1% post-exercise was indicative of EIB. The results from both tests were compiled in a 2x2 table, using MCT as the reference standard. Results Out of the 98 patients who underwent CPET, 53 also completed a methacholine challenge test. The mean age of participants was 14 years (SD ± 2.42), with a mean BMI of 22.2 kg/m² (SD ± 5.25), and 71% of the patients were female. Using CPET as the reference standard, the MCT demonstrated a sensitivity of 66.7%, specificity of 58%, positive predictive value of 8.7%, and a negative predictive value of 96.7% for identifying BHR in patients with exertional dyspnea. Conclusions MCT exhibited moderate sensitivity and specificity, and a high negative predictive value, indicating its effectiveness in ruling out BHR in children with exertional dyspnea. However, it is less reliable as a standalone diagnostic tool for EIB, and CPET remains essential for an accurate diagnosis of EIB in these patients.