Ventilatory Limitation of Exercise in Pediatric Subjects Evaluated for Exertional Dyspnea

Purpose: Attribution of ventilatory limitation to exercise when the ratio of ventilation (V˙E) at peak work to maximum voluntary ventilation (MVV) exceeds 0.80 is problematic in pediatrics. Instead, expiratory flow limitation (EFL) measured by tidal flow-volume loop (FVL) analysis – the method of choice – was compared with directly measured MVV or proxies to determine ventilatory limitation.Methods: Subjects undergoing clinical evaluation for exertional dyspnea performed maximal exercise testing with measurement of tidal FVL. EFL was defined when exercise tidal FVL overlapped at least 5% of the maximal expiratory flow-volume envelope for > 5 breaths in any stage of exercise. We compared this method of ventilatory limitation to traditional methods based on MVV or multiples (30, 35, or 40) of FEV1. Receiver operating characteristic curves were constructed and area under curve (AUC) computed for peak V˙E/MVV and peak V˙E/x⋅FEV1.Results: Among 148 subjects aged 7–18 years (60% female), EFL was found in 87 (59%). Using EFL shown by FVL analysis as a true positive to determine ventilatory limitation, AUC for peak V˙E/30⋅FEV1 was 0.84 (95% CI 0.78–0.90), significantly better than AUC 0.70 (95% CI 0.61–0.79) when 12-s sprint MVV was used for peak V˙E/MVV. Sensitivity and specificity were 0.82 and 0.70 respectively when using a cutoff of 0.85 for peak V˙E/30⋅FEV1 to predict ventilatory limitation to exercise.Conclusion: Peak V˙E/30⋅FEV1 is superior to peak V˙E/MVV, as a means to identify potential ventilatory limitation in pediatric subjects when FVL analysis is not available

The Clinical Translation Gap in Child Health Exercise Research: A Call for Disruptive Innovation: ThePediatricExerciseNetwork-WorkingGroup

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Postural Orthostatic Tachycardia Syndrome: A Respiratory Disorder?

Postural orthostatic tachycardia syndrome (POTS) is a disorder epitomized by the story of the blind men and the elephant. Patients may see primary care internists or pediatricians due to fatigue, be referred to neurologists for spells , to cardiologists for evaluation of pre-syncope or chest pain, to gastroenterologists for nausea or dyspepsia, and even pulmonologists for dyspnea. Adoption of a more systematic approach to their evaluation and better characterization of patients has led to greater understanding of comorbidities, hypotheses prompting mechanistic investigations, and pharmacologic trials. Recent work has implicated disordered sympathetic nervous system activation in response to central (thoracic) hypovolemia. It is this pathway that leads one zero in on a putative focal point from which many of the clinical manifestations can be explained - specifically the carotid body. Despite heterogeneity in etiopathogenesis of a POTS phenotype, we propose that aberrant activation and response of the carotid body represents one potential common pathway in evolution. To understand this postulate, one must jettison isolationist or reductionist ideas of chemoreceptor and baroreceptor functions of the carotid body or sinus, respectively, and consider their interaction and interdependence both locally and centrally where some of its efferents merge. Doing so enables one to connect the dots and appreciate origins of diverse manifestations of POTS, including dyspnea for which the concept of neuro-mechanical uncoupling is wanting, thereby expanding our construct of this symptom. This perspective expounds our premise that POTS has a prominent respiratory component

Pediatric Exercise Testing: Value and Implications of Peak Oxygen Uptake

Peak oxygen uptake (peak V ˙ O 2 ) measured by clinical exercise testing is the benchmark for aerobic fitness. Aerobic fitness, estimated from maximal treadmill exercise, is a predictor of mortality in adults. Peak V ˙ O 2 was shown to predict longevity in patients aged 7–35 years with cystic fibrosis over 25 years ago. A surge of exercise studies in young adults with congenital heart disease over the past decade has revealed significant prognostic information. Three years ago, the first clinical trial in children with pulmonary arterial hypertension used peak V ˙ O 2 as an endpoint that likewise delivered clinically relevant data. Cardiopulmonary exercise testing provides clinicians with biomarkers and clinical outcomes, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response hidden at rest. Momentum from these pioneering observations in multiple disease states should impel clinicians to employ similar methods in other patient populations; e.g., sickle cell disease. Advances in pediatric exercise science will elucidate new pathways that may identify novel biomarkers. Our initial aim of this essay is to highlight the clinical relevance of exercise testing to determine peak V ˙ O 2 , and thereby convince clinicians of its merit, stimulating future clinical investigators to broaden the application of exercise testing in pediatrics

Pediatric Disorders of Orthostatic Intolerance

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, approximately 40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management

The clinical translation gap in child health exercise research: a call for disruptive innovation.

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health