Resting energy expenditure in children at risk of hypothalamic dysfunction.

Objective: Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage. Patients and methods: A retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage. Results: In total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE. Conclusion: REE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.

Long-term effects of ivacaftor on nonpulmonary outcomes in individuals with cystic fibrosis, heterozygous for a S1251N mutation.

OBJECTIVES: To describe the long-term effects of ivacaftor (Kalydeco®) in individuals with cystic fibrosis (CF) on body mass index (BMI), body composition (BC), pulmonary function (PF), resting energy expenditure (REE), and exercise capacity (EC) after ≥12 months of treatment. WORKING HYPOTHESIS: BMI, lean and fat mass, PF, and EC will increase and REE will decrease after treatment. STUDY DESIGN: Observational study. METHODOLOGY: Seven individuals with CF (mean age 15.4 ± 5.8 years) heterozygous for S1251N mutation, starting with ivacaftor, were included. Paired t tests were performed to assess the effects of ivacaftor. Height and weight were used to calculate BMI and BMI Z-scores. Dual-energy X-ray absorptiometry was used to assess BC. Spirometry and body plethysmography were used to assess PF. Indirect calorimetry was used to measure REE and cardiopulmonary exercise testing (CPET) was used to measure oxygen uptake (VO2peak ), peak work rate (Wpeak ), and other CPET variables. RESULTS: After a median of 15 (interquartile range: 13-16) months of treatment, BMI increased significantly (P = .03), but not BMI Z-score (P = .23) or BC. Significant improvements were found for several PF variables, especially measures of hyperinflation (P = .02). Absolute VO2peak (P = .01), VO2peak related to body weight (P = .00), and oxygen cost of work (P = .01) decreased. Absolute Wpeak (P = .59) and Wpeak related to body weight (P = .31) remained stable. CONCLUSIONS: The results showed that long-term treatment of ivacaftor is associated with improvement of BMI and PF, but not of BC and REE. Oxygen uptake reduced after treatment, which may be due to a decrease in work of breathing.

Cost-effectiveness of a combined physical exercise and psychosocial training intervention for children with cancer: Results from the quality of life in motion study.

This study was performed to estimate the cost-effectiveness of a combined physical exercise and psychosocial intervention for children with cancer compared with usual care. Sixty-eight children, aged 8-18 years old, during or within the first year post-cancer treatment were randomised to the intervention (n = 30) and control group (n = 38). Health outcomes included fitness, muscle strength and quality adjusted life years; all administered at baseline, 4- and 12-month follow-up. Costs were gathered by 1 monthly cost questionnaires over 12 months, supplemented by medication data obtained from pharmacies. Results showed no significant differences in costs and effects between the intervention and control group at 12-month follow-up. On average, societal costs were €299 higher in the intervention group than in the control group, but this difference was not significant. Cost-effectiveness acceptability curves indicated that the intervention needs large societal investments to reach reasonable probabilities of cost-effectiveness for quality of life and lower body muscle strength. Based on the results of this study, the intervention is not cost-effective in comparison with usual care.

Relationship between lung function and Modified Shuttle Test performance in adult patients with cystic fibrosis: a cross-sectional, retrospective study.

OBJECTIVES: To investigate the relationship between lung function and exercise capacity in adults with cystic fibrosis (CF), and to develop a CF-specific equation to predict Modified Shuttle Test (MST) performance from baseline data. DESIGN: Cross-sectional, retrospective study. SETTING: Adult CF centre. PARTICIPANTS: One hundred and twenty-seven patients with CF [61 male; mean age 25 years (range 17 to 52 years), mean forced expiratory volume in 1second (FEV1) 56% predicted (range 15 to 124%)]. MAIN OUTCOME MEASURES: MST and FEV1. RESULTS: Overall, a moderate-to-good relationship was found between lung function and MST performance (walking distance vs FEV1% predicted: r=0.64, P=0.01). This relationship between FEV1 and MST shows an obvious threshold at an FEV1 of 67% predicted. Above this threshold, no significant association was observed between FEV1 and MST performance. However, a strong relationship (MST vs FEV1% predicted: r≥0.74, P<0.01 for men and r=0.79, P<0.01 for women) was found below an FEV1 of 67% predicted. CONCLUSIONS: This study suggests that a strong association exists between lung function (FEV1% predicted) and MST (walking distance) in adult patients with moderate-to-severe CF (FEV1<67% predicted). A reference equation for MST performance was developed for those patients with FEV1 ≤67% predicted, providing a tool to make an a-priori prediction of MST walking distance.

Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl-carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD.

Application of the steep ramp test for aerobic fitness testing in children with cancer.

BACKGROUND: Children with and after cancer are found to have a decreased physical fitness, frequently resulting in decreased physical functioning. The gold standard test for assessing aerobic fitness, a component of physical fitness, is the respiratory gas analyses-based cardiopulmonary exercise test (CPET). However, equipment for gas analysis is often unavailable in local physical therapy centres and non-university hospitals. The steep ramp test (SRT), is a cycle ergometer test with a fast increase in workload, a short duration, and does not require respiratory gas analysis equipment. AIM: The aim of this study was to compare the results of the CPET and the SRT, in children with cancer, and to assess whether the SRT can be used for aerobic fitness assessment in clinical practice in this population. DESIGN: This study is a cross-sectional assessment using baseline data of a randomized controlled trial. SETTING: The study was performed in a hospital setting. POPULATION: Sixty-one children (mean age 12.9 years; 33 boys) with cancer were included in the analysis; 16 children were on non-intensive chemotherapy treatment, 45 were in the first year thereafter. METHODS: Participants performed both the SRT and the CPET on a cycle ergometer with respiratory gas analysis. Data of the two tests were compared and regression analyses were performed. RESULTS: CPET test results revealed a higher impact on the cardiovascular system, as shown by higher peak ventilation (47.8 versus 52.0 Litres per min) and peak heart rates (173 versus 191 beats per min), compared to the SRT. In addition, the test time was significantly longer (90 s versus 390 s). Yet, the primary outcome of the SRT (peak work rate) was able to reliably estimate the peak oxygen uptake of the CPET. CONCLUSION: The peak oxygen uptake was comparable between the SRT and the CPET, although the peak work rate was significantly higher during the SRT. This study showed that the SRT is a valid instrument to assess aerobic fitness in children with cancer. CLINICAL REHABILITATION IMPACT: The SRT is less time consuming and can be performed without gas analysis in a non-clinical setting, making it less demanding for children.

Towards an individualized protocol for workload increments in cardiopulmonary exercise testing in children and adolescents with cystic fibrosis.

BACKGROUND: There is no single optimal exercise testing protocol for children and adolescents with cystic fibrosis (CF) that differs widely in age and disease status. The aim of this study was to develop a CF-specific, individualized approach to determine workload increments for a cycle ergometry testing protocol. METHODS: A total of 409 assessments consisting of maximal exercise data, anthropometric parameters, and lung function measures from 160 children and adolescents with CF were examined. 90% of the database was analyzed with backward linear regression with peak workload (W(peak)) as the dependent variable. Afterwards, we [1] used the remaining 10% of the database (model validation group) to validate the model's capacity to predict W(peak) and [2] validated the protocol's ability to provide a maximal effort within a 10±2 minute time frame in 14 adolescents with CF who were tested using this new protocol (protocol validation group). RESULTS: No significant differences were seen in W(peak) and predicted W(peak) in the model validation group or in the protocol validation group. Eight of 14 adolescents with CF in the protocol validation group performed a maximal effort, and seven of them terminated the test within the 10±2 minute time frame. Backward linear regression analysis resulted in the following equation: W(peak) (W)=-142.865+2.998×Age (years)-19.206×Sex (0=male; 1=female)+1.328×Height (cm)+23.362×FEV(1) (L) (R=.89; R(2)=.79; SEE=21). Bland-Altman analysis showed no systematic bias between the actual and predicted W(peak). CONCLUSION: We developed a CF-specific linear regression model to predict peak workload based on standard measures of anthropometry and FEV(1), which could be used to calculate individualized workload increments for a cycle ergometry testing protocol.

Exercise and inflammation in pediatric Crohn's disease.

We examined inflammatory cells, cytokines and growth factors in response to acute bouts of moderate intensity continuous exercise and high intensity intermittent exercise in youth with Crohn's disease and in healthy matched-controls. 15 patients and 15 controls performed 30 min of cycling at 50% of peak mechanical power (PMP) and 6 bouts of 4×15-s of cycling at 100% PMP. Blood was collected at rest, at the mid-point, at the end of exercise and at 30 and 60 min into recovery. In patients with CD, both types of exercise increased immune cells and GH and decreased IGF-I. Moderate intensity exercise induced a greater increase in leukocytes (p<0.05), neutrophils (p<0.05), lymphocytes (p<0.001), monocytes (p<0.05), IL-6 (p<0.05), IL-17 (p<0.05) and GH (p<0.05) and a similar decrease in IGF-I, compared with high intensity exercise. TNF-α did not change significantly with either exercise. Responses in patients were similar compared with controls; however, in patients monocytes remained elevated significantly longer in response to MICE. Youth with Crohn's disease can engage in distinctly different types of exercise without a significant acute exacerbation of inflammation.

Is static hyperinflation a limiting factor during exercise in adolescents with cystic fibrosis?

Increased work of breathing is considered to be a limiting factor in patients with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that adolescents with CF and with static hyperinflation are more prone to a ventilatorily limited exercise capacity than non-static hyperinflated adolescents with CF. Exercise data of 119 adolescents with CF [range 12-18 years], stratified for static hyperinflation, defined as ratio of residual volume to total lung capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer test with gas analysis and analyzed for ventilatory limitation. Static hyperinflation showed a significant, though weak association (Φ 0.38; P < 0.001) with a ventilatorily limited exercise capacity (breathing reserve index at maximal effort >0.70; FEV(1) < 80% predicted and reduced exercise capacity, defined as VO(2peak) < 85% predicted). Analysis of association for increasing degrees of hyperinflation showed an increase to Φ 0.49 (P < 0.001) for RV/TLC > 50%. In adolescents with static hyperinflation, peak work rate (W(peak) ; 3.1 ± 0.7 W/kg (75.1 ± 17.3% of predicted), peak oxygen uptake (VO(2peak) /kg (ml/min/kg); 39.2 ± 9.2 ml/min/kg (91.0 ± 20.3% of predicted), peak heart rate (HR(peak) ; 176 ± 19 beats/min) were significantly (P < 0.05) decreased when compared with non-static hyperinflated adolescents (W(peak) 3.5 ± 0.5 W/kg (81.4 ± 10.0% of predicted)); VO(2peak) /kg (ml/min/kg); 43.1 ± 7.5 ml/min/kg (98.0 ± 15.1% of predicted); and HR(peak) 185 ± 14 beats/min). Additionally, no difference was found in the degree of association of FEV(1) (%) and RV/TLC (%) with VO(2peak) /kg(pred) and W(peak) /kg(Pred) , but we found the RV/TLC (%) to be a slightly stronger predictor of VO(2peak) /kg(pred) and W(peak) /kg(Pred) than FEV(1) (%). These results indicate that the presence of static hyperinflation in adolescents with CF by itself does not strongly influence ventilatory constraints during exercise and that static hyperinflation is only a slightly stronger predictor of W(peak) /kg(Pred) and VO(2peak) /kg(Pred) than airflow obstruction (FEV(1) (%)).

High-intensity interval training in an adolescent with cystic fibrosis: a physiological perspective.

Nutritional, musculoskeletal, and/or ventilatory status can lead to a decreased exercise capacity in children with cystic fibrosis (CF). Exercise training is already part of the usual care; however, the "optimal" intensity and volume of exercise training to improve exercise capacity is still unknown. Six weeks of high-intensity interval training (HIT) for a patient with CF with a ventilatory limitation was evaluated by a cardiopulmonary exercise test (CPET). Peak oxygen uptake and peak workload increased 19% and 16%, respectively, and there was a rise in peak ventilation from 50 L/min to 75 L/min, with an increase in both breathing depth and respiratory rate. A relative short period of HIT resulted in a significant increase in exercise capacity. In patients with CF, HIT might be an effective and efficient training regimen, especially in CF patients with a ventilatory limitation. Further research is necessary to investigate whether HIT is a better alternative than traditional aerobic training programs especially in ventilatory limited patients with CF.

Validation of the Actiheart activity monitor for measurement of activity energy expenditure in children and adolescents with chronic disease.

BACKGROUND/OBJECTIVES: The purpose of this study was to develop an activity energy expenditure (AEE) prediction equation for the Actiheart activity monitor for use in children with chronic disease. SUBJECTS/METHODS: In total, 63 children, aged 8-18 years with different types of chronic disease (juvenile arthritis, hemophilia, dermatomyositis, neuromuscular disease, cystic fibrosis or congenital heart disease) participated in an activity testing session, which consisted of a resting protocol, working on the computer, sweeping, hallway walking, steps and treadmill walking at three different speeds. During all activities, actual AEE was measured with indirect calorimetry and the participants wore an Actiheart on the chest. Resting EE and resting heart rate were measured during the resting protocol and heart rate above sleep (HRaS) was calculated. RESULTS: Mixed linear modeling produced the following prediction equation: This equation results in a nonsignificant mean difference of 2.1 J/kg/min (limits of agreement: -144.2 to 148.4 J/kg/min) for the prediction of AEE from the Actiheart compared with actual AEE. CONCLUSIONS: The Actiheart is valid for the use of AEE determination when using the new prediction equation for groups of children with chronic disease. However, the prediction error limits the use of the equation in individual subjects.

Oxygen uptake to work rate slope in children with a heart, lung or muscle disease.

The purposes of this study were all to determine if DeltaVO2/DeltaWR is dependent on age, body mass, height and fitness and if DeltaVO2/DeltaWR could discriminate between healthy children and children with a chronic disease that limits O2 delivery or utilization. Four groups were included: muscle disease (Juvenile Dermatomyositis; JDM; n=12), lung disease (Cystic Fibrosis; CF; n=13), Congenital Heart Disease (CHD; (n=13), and healthy children (n=44). All children performed a cardiopulmonary exercise test on a cycle ergometer with respiratory gas analysis. The DeltaVO2/DeltaWR was determined by linear regression using data from unloaded cycling to peak exercise. No associations were found between the DeltaVO2/DeltaWR and age, body mass and height in healthy children. DeltaVO2/DeltaWR was significantly correlated with VO2peak/kg (r=0.44; p<0.01). Children with JDM had lower DeltaVO2/DeltaWR values than healthy children (p=0.02), and DeltaVO2/DeltaWR tended to be lower in CHD and higher in CF (p=0.09 and p=0.08, respectively). DeltaVO2/DeltaWR may be more sensitive for conditions that are characterized by local hypo perfusion (as in JDM), than for conditions that are characterized by impaired oxygen delivery (i. e. CF or CHD).

Exercise tolerance in children with juvenile idiopathic arthritis after autologous SCT.

Children with juvenile idiopathic arthritis (JIA) often have significant physical impairment. A minority is unresponsive to combinations of medications, and a possible treatment of resistant JIA is intense immunosuppression followed by autologous hematopoietic SCT (ASCT). Children resistant to conventional therapy have a poor prognosis with regard to long-term outcome of joint function, exercise tolerance and quality of life. It has previously been shown that ASCT can induce long-term remissions in such children. The long-term effects of this treatment are still largely unknown. This retrospective study investigates the exercise tolerance and functional ability in children with JIA who have undergone ASCT compared to healthy subjects. Ten children with JIA who received ASCT between 1997 and 2003 participated in this study. Patients were tested during their regular clinical follow-up. Exercise tolerance was determined using a maximal exercise test. Functional ability was measured using the Childhood Health Assessment Questionnaire and joint status. The study group showed significantly reduced exercise tolerance compared to healthy subjects. Functional ability and joint status were also decreased in patients after ASCT. Children with JIA postASCT have impaired exercise tolerance even 9 years postASCT.

Exercise testing in children and adolescents with chronic fatigue syndrome.

The objective of this study was to evaluate exercise capacity in children and adolescents diagnosed with Chronic Fatigue Syndrome (CFS). We examined 20 patients (12 girls and 8 boys; mean age 14.9 +/- 3.7 years) diagnosed with CFS. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Fatigue was assessed using a questionnaire and a daily activity diary was used to describe activities for three days. Z-scores were calculated using age- and sex-matched reference values. Z-scores in children and adolescents with CFS were - 0.33 +/- 1.0 (p = 0.17) for peak oxygen uptake, - 1.13 +/- 1.41 (p = 0.002) for relative peak oxygen uptake [ml/kg/min] and - 0.93 +/- 1.29 (p = 0.07) for maximal work load. Both heart rate and blood pressure at peak performance were significantly reduced compared to reference values. Fatigue levels were significantly positively associated with age and negatively with blood pressure at peak exercise (p < 0.05). In conclusion maximum exercise testing was feasible in young people with CFS. Maximal exercise capacity was only reduced in a minority of the patients and was related to current physical activity levels.

Is physical fitness decreased in survivors of childhood leukemia? A systematic review.

The aim of this review is to determine whether physical fitness, assessed by peak oxygen uptake (VO(2peak)) measurement, is reduced in survivors of acute lymphoblastic leukemia (ALL) compared to healthy children. A systematic literature search (up to June 2004) was performed using Medline, Sportdiscus, Cinahl, Embase, Cochrane and PEDro database and reference tracking. The VO(2peak) (ml kg(-1) min(-1)) reached during a maximal exercise test until volitional exhaustion was used as the main outcome for this review. In all, 17 studies were identified in the literature. Data from three studies (102 ALL survivors, age ranging from 7 to 19 years) were pooled in a meta-analysis. Although there was a significant heterogeneity between the included studies (P=0.0006), the standardized mean difference (SMD) value of -0.61 (P=0.07) indicated that VO(2peak) tended to be reduced in survivors of childhood ALL compared to healthy control subjects, that is, decrease of -5.97 ml kg(-1) min(-1) (95% confidence interval (CI): (-12.35, 0.41); P=0.07) or -13% (95 % CI: (-27, 0.004)). Physical fitness tends to be reduced in survivors of ALL during childhood, which suggests the need for this population group to engage in regular physical activities with the purpose of increasing their functional capacity. Although more research is needed, this functional improvement might ameliorate the quality of life of ALL survivors as physical and outdoors activities are an essential part of daily routine during childhood.