Puentes, G.A. Cortes

Mechanical ventilation remains a cornerstone of acute respiratory failure management, but ventilator-induced lung injury persists despite lung-protective strategies focused on limiting tidal volume (V T ), plateau pressure, and driving pressure. Mechanical power has emerged as a comprehensive metric that quantifies the total energy delivered to the lungs per unit time by integrating V T , airway pressures, breathing frequency, flow, and PEEP into a single physiologic measure. Observational studies through 2025 show that elevated mechanical power is associated with worse outcomes, including increased mortality, fewer ventilator-free days, and longer ICU stays, with breathing frequency identified as a major contributor even when other settings remain within protective ranges. Although no universal injurious threshold exists because of patient variability, normalization strategies such as indexing mechanical power to predicted body weight or respiratory system compliance have shown promise in improving prognostic value, although consensus on the optimal method is lacking. Currently, mechanical power should be considered a complementary bedside tool that integrates multiple ventilator variables, helps identify key contributors to lung stress and strain, and may support individualized ventilator adjustments to reduce cumulative injury risk as further evidence and technology evolve.

Abstract Rationale Bronchial hyperreactivity (BHR) is a hallmark of asthma, frequently presenting as exercise-induced dyspnea in children and adolescents. Identifying BHR is essential for accurate diagnosis and management of exercise symptoms. The methacholine challenge test (MCT) is the gold standard for diagnosing BHR due to its high sensitivity in detecting airway hyperresponsiveness. However, the MCT requires specialized equipment and stringent protocols, which can limit its availability and use in some clinical settings. An alternative approach, the bronchodilator response test (BDR), is more accessible and assesses the reversibility of airway obstruction following bronchodilator administration. BDR testing is a routine component of asthma diagnostics for evaluating airflow limitation, making it a potentially useful tool for BHR assessment. However, the ability of BDR testing to reliably detect BHR in exertional dyspnea is still uncertain. Prior research has shown that BDR testing, while specific, has low sensitivity for BHR when compared to the MCT, raising questions about its standalone utility in clinical practice. The objective of this study was to evaluate the diagnostic performance of the BDR in detecting bronchial hyperreactivity in exertional dyspnea, using the MCT as the reference standard. By analyzing sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), we aimed to assess whether BDR testing could serve as a reliable alternative to MCT for diagnosing BHR. Methods We conducted a retrospective study of pediatric patients who underwent cardiopulmonary exercise testing, BDR, and MCT as part of their assessment for exertional dyspnea from July 2020 to February 2023. Patients up to 18 years of age were included. A positive BDR was defined by a 10% or greater improvement in FEV1% or FVC%, while a positive MCT was defined by a 20% reduction in FEV1%. Data are presented in a 2x2 table, with the MCT as the reference standard. Results and Conclusion In a cohort of 98 patients, 20 underwent both bronchodilator and methacholine testing. The BDR test, using MCT as the reference, showed a sensitivity of 16.7%, specificity of 87.5%, PPV of 66.7%, and NPV of 41.2%. These results suggest that, due to its low sensitivity, BDR testing alone is insufficient for BHR detection when clinical suspicion of asthma is high. The MCT remains the preferred diagnostic method, though using both tests may provide a more comprehensive evaluation of airway reactivity in children presenting with exercise symptoms.

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.

Abstract Rationale: Cardiopulmonary exercise testing is a unique tool for simultaneously assessing cardiopulmonary and metabolic responses at peak exercise, making it invaluable for diagnosing unexplained dyspnea and fatigue, common issues in cardiovascular and pulmonary clinics. However, its use is often limited by complex guidelines, restricted lab access, technical demands, and high costs. The Veterans Specific Activity Questionnaire (VSAQ), developed by Meyers et al., offers a practical way to estimate metabolic equivalents and maximum oxygen consumption to assess exercise capacity. While primarily validated in a male population, the VSAQ lacks sufficient research in diverse ethnic and gender groups. Broader validation could enhance personalized cardiopulmonary testing, support equitable healthcare resource allocation, and help lower costs. Methods: In this prospective observational study, participants were included if they were 18 years or older and capable of completing a cardiopulmonary exercise test. Participants were excluded if they had known abnormal breathing patterns at baseline and if they had any contraindication for cardiopulmonary exercise and pulmonary function testing. A total of 17 patients without known cardiopulmonary disease provided informed consent and completed the brief self-administered VSAQ following the cardiopulmonary exercise test. The VSAQ was used to estimate maximal exercise capacity in metabolic equivalents, which was then compared to the actual maximal exercise capacity achieved on a bike ergometer, as recorded in the electronic medical records. Results: A linear regression analysis indicated a marginal association between VSAQ results (METS) and CPET METS, accounting for 22.2% of the variance in CPET METS (p=0.056). This finding suggests a potential, though not statistically significant, positive relationship between VSAQ METS scores and CPET MET. A linear regression analysis indicated a marginal association between VSAQ calculated Peak VO₂ and observed CPET Peak VO₂ (o₂/kg/min), explaining 21.6% of the variance in CPET Peak VO₂ (p=0.060). This suggests a potential positive relationship between VSAQ calculated Peak VO₂ and CPET Peak VO₂, though the association did not reach statistical significance. Conclusion: In this preliminary sample of patients without known cardiopulmonary disease, the VSAQ demonstrated accuracy in predicting maximum oxygen consumption at peak exercise. With further validation and larger sample size, the VSAQ could become a valuable adjunctive tool for assessing patients with unexplained dyspnea and fatigue, supporting more efficient diagnostic evaluations. Additionally, the VSAQ may serve as a practical follow-up measure to track clinical improvement after therapeutic interventions in this specific population.