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.

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.

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects.

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.

Development of an unsupported arm exercise test in patients with chronic obstructive pulmonary disease.

BACKGROUND: Unsupported arm exercise tests have been used to evaluate the effects of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), but the reliability and validity of these tests are not established. OBJECTIVE: We evaluated the test-retest reliability and validity of a 6-minute pegboard and ring test (PBRT) in 27 outpatients with COPD and 30 age-matched controls. METHODS: We evaluated a 6-minute PBRT, subject demographics, pulmonary function and disease-specific quality of life questionnaire, and the Pulmonary Functional Status Dyspnea Questionnaire-Modified version in 27 patients with COPD. RESULTS: Highly significant correlation coefficients (r = .91, P < .001) were found between test and retest of PBRT scores. Statistically significant correlation coefficients were found between PBRT scores and pulmonary function tests such as FEV1% pred and FVC% pred, and activity domain and subdomain of Pulmonary Functional Status Dyspnea Questionnaire-Modified (P

Arm work interferes with normal ventilation.

Arm work, by limiting movement of the chest wall and use of the respiratory muscles, may alter breathing pattern and gas exchange sufficiently to interfere with the ability to perform certain tasks. To determine the effects of arm work on breathing pattern during a well-controlled work task, depth of breathing, breathing frequency and end-expiratory lung volume (EELV) were measured at rest and during cycling exercise using an arm and a leg ergometer. Six subjects performed arm work at light, moderate and heavy intensities (30%, 60% and 90% of maximum arm work capacity respectively) and leg work at three intensities where ventilation was matched for that achieved during the arm work. This matching was necessary since the level of ventilation affects the breathing pattern. Subjects breathed on a mouthpiece and tubing that led to automated equipment for the measurement of respiratory variables. Ventilation during arm work was accomplished with a lower depth of breathing, a higher breathing frequency and a decreased EELV compared to leg work. Arm work places increased demands on the ventilatory system, including the muscles of respiration that are also recruited for task performance. The competition for using these muscles for breathing as opposed to a particular work task may result in a compromise in breathing capacity that ultimately may limit the ability to perform tasks requiring sustained heavy use of the arms. These increased demands on the upper body muscles must be considered when evaluating the ability of individuals to perform tasks that involve heavy arm work.

Physiologic evidence for the efficacy of positive expiratory pressure as an airway clearance technique in patients with cystic fibrosis.

BACKGROUND AND PURPOSE: Individuals with cystic fibrosis (CF) have large amounts of infected mucus in their lungs, which causes irreversible lung tissue damage. Although patient-administered positive expiratory pressure (PEP) breathing has been promoted as an effective therapeutic modality for removing mucus and improving ventilation distribution in these patients, the effects of PEP on ventilation distribution and gas mixing have not been documented. Therefore, this preliminary investigation described responses in distribution of ventilation and gas mixing to PEP breathing for patients with moderate to severe CF lung disease. SUBJECTS AND METHODS: The effects of PEP breathing on ventilation distribution, gas mixing, lung volumes, expiratory airflow, percentage of arterial blood oxyhemoglobin saturation (SpO(2)), and sputum volume were studied in 5 patients with CF (mean age=18 years, SD=4, range=13-22) after no-PEP, low-PEP (10-20 cm H(2)O), and high-PEP (>20 cm H(2)O) breathing conditions. Single-breath inert gas studies and lung function tests were performed before, immediately after, and 45 minutes after intervention. Single-breath tests assess ventilation distribution homogeneity and gas mixing by observing the extent to which an inspired test gas mixes with gas already residing in the lung. RESULTS: Improvements in gas mixing were observed in all PEP conditions. By 45 minutes after intervention, the no-PEP group improved by 5%, the low-PEP group improved by 15%, and the high-PEP group improved by 23%. Slow vital capacity increased by 1% for no PEP, by 9% for low PEP, and by 13% for high PEP 45 minutes after intervention. Residual volume decreased by 13% after no PEP, by 20% after low PEP, and by 30% after high PEP. Immediate improvements in forced expiratory flow during the middle half of the forced vital capacity maneuver (FEF(25%-75%)) were sustained following high PEP but not following low PEP. DISCUSSION AND CONCLUSION: This study demonstrated the physiologic basis for the efficacy of PEP therapy. The results confirm that low PEP and high PEP improve gas mixing in individuals with CF, and these improvements were associated with increased lung function, sputum expectoration, and SpO(2). The authors propose that improvements in gas mixing may lead to increases in oxygenation and thus functional exercise capacity.

Ventilatory response to exercise in simulated obesity by chest loading.

INTRODUCTION & PURPOSE: Obesity-related increases of weight on the chest wall are known to decrease lung volume and chest wall compliance, but the effect of this mass loading, independent of other obesity-related complications on the ventilatory response to exercise is unknown. The purpose of this study was to investigate the effect of chest mass loading on the ventilatory response to exercise. METHODS: External chest loading (CL) was used to simulate the effect of moderate obesity (BMI = 32 kg x m). Eight healthy nonobese subjects performed two incremental exercise tests on a cycle ergometer with work rate increasing 25 W every 3 min once without (control; CON) and once with CL. Expiratory reserve volume (ERV), forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were measured before each test. During exercise, inspiratory capacity (IC), to estimate changes in end-expiratory lung volume, and inspiratory (TI) and expiratory (TE) duration, tidal volume (Vt), breathing frequency (Fb), minute ventilation (VE), mean inspiratory (Vt/TI) and expiratory (Vt/TE) flow rates, and oxygen consumption (VO2) were measured. RESULTS: Baseline ERV, FVC and FEV1 were lower with CL (P < 0.05). Compared with CON, the peak work rate achieved during exercise with CL was lower and VO2, VE, Fb, Vt/TI, and Vt/TE were higher, and Vt was lower at work rates > or = 100 W (P < 0.05). IC increased progressively in CON during exercise but remained unchanged with CL. CONCLUSION: Obesity-related chest loading decreases lung volumes and increases the mechanical ventilatory constraints during exercise and is likely a critical factor in reducing exercise capacity in obesity.

Neandertal cold adaptation: physiological and energetic factors.

European Neandertals employed a complex set of physiological cold defenses, homologous to those seen in contemporary humans and nonhuman primates. While Neandertal morphological patterns, such as foreshortened extremities and low relative surface-area, may have explained some of the variance in cold resistance, it is suggested the adaptive package was strongly dependent on a rich array of physiological defenses. A summary of the environmental cold conditions in which the Neandertals lived is presented, and a comparative ethnographic model from Tierra del Fuego is used. Muscle and subcutaneous fat are excellent "passive" insulators. Neandertals were quite muscular, but it is unlikely that they could maintain enough superficial body fat to offer much cold protection. A major, high-energy metabolic adaptation facilitated by modest amounts of highly thermogenic brown adipose tissue (BAT) is proposed. In addition, Neandertals would have been protected by general mammalian cold defenses based on systemic vasoconstriction and intensified by acclimatization, aerobic fitness, and localized cold--induced vasodilation. However, these defenses are energetically expensive. Based on contemporary data from circumpolar peoples, it is estimated that Neandertals required 3,360 to 4,480 kcal per day to support strenuous winter foraging and cold resistance costs. Several specific genetic cold adaptations are also proposed--heat shock protein (actually, stress shock protein), an ACP*1 locus somatic growth factor, and a specialized calcium metabolism not as yet understood.

Exercise and Cystic Fibrosis: A Review.

Cystic fibrosis (CF) results in chronic obstructive pulmonary disease with progressive increases in areas of the lung with poor gas exchange (dead space). The pulmonary response to exercise is characterized by a higher than expected minute ventilation (V̇E). In some patients the elevated V̇Eis inadequate to overcome the large dead space, resulting in decreases in arterial oxygen and/or increases in arterial carbon dioxide levels during exercise. Chronic lung hyperinflation in patients with severe disease limits the ability to increase tidal volume, and therefore V̇E, during exercise. Most patients can exercise without decreases in arterial oxygen and should be encouraged to participate in regular activity. Oxygen supplementation during exercise allows many patients with severe lung dysfunction to participate in some form of activity. Regular exercise has been shown to be of some benefit and should be encouraged on an individual basis in patients with CF.