Mechanisms of ventilatory limitation to maximum exercise in children and adolescents with chronic airway diseases.

INTRODUCTION: Exercise intolerance is common in chronic airway diseases (CAD), but its mechanisms are still poorly understood. The aim of this study was to evaluate exercise capacity and its association with lung function, ventilatory limitation, and ventilatory efficiency in children and adolescents with cystic fibrosis (CF) and asthma when compared to healthy controls. METHODS: Cross-sectional study including patients with mild-to-moderate asthma, CF and healthy children and adolescents. Anthropometric data, lung function (spirometry) and exercise capacity (cardiopulmonary exercise testing) were evaluated. Primary outcomes were peak oxygen consumption (VO2 peak), forced expiratory volume in 1 s (FEV1 ), breathing reserve (BR), ventilatory equivalent for oxygen consumption (VE /VO2 ) and for carbon dioxide production (VE /VCO2 ), both at the ventilatory threshold (VT1 ) and peak exercise. RESULTS: Mean age of 147 patients included was 11.8 ± 3.0 years. There were differences between asthmatics and CF children when compared to their healthy peers for anthropometric and lung function measurements. Asthmatics showed lower VO2 peak when compared to both healthy and CF subjects, although no differences were found between healthy and CF patients. A lower BR was found when CF patients were compared to both healthy and asthmatic. Both CF and asthmatic patients presented higher values for VE /VO2 and VE /VCO2 at VT1 when compared to healthy individuals. For both VE /VO2 and VE /VCO2 at peak exercise CF patients presented higher values when compared to their healthy peers. CONCLUSION: Patients with CF achieved good exercise capacity despite low ventilatory efficiency, low BR, and reduced lung function. However, asthmatics reported reduced cardiorespiratory capacity and normal ventilatory efficiency at peak exercise. These results demonstrate differences in the mechanisms of ventilatory limitation to maximum exercise testing in children and adolescents with CAD.

Comparison of physical fitness between healthy and mild-to-moderate asthmatic children with exercise symptoms: A cross-sectional study.

OBJECTIVE: Asthma is a chronic disease that may affect physical fitness, although its primary effects on exercise capacity, muscle strength, functionality and lifestyle, in children and adolescents, are still poorly understood. This study aimed to evaluate the differences in cardiorespiratory fitness, muscle strength, lifestyle, lung function, and functionality between asthmatics with exercise symptoms and healthy children. In addition, we have analyzed the association between clinical history and the presence of asthma. STUDY DESIGN: Cross-sectional study including 71 patients with a diagnosis of asthma and 71 healthy children and adolescents (7-17 years of age). Anthropometric data, clinical history, disease control, lifestyle (KIDMED and physical activity questionnaires), lung function (spirometry), exercise-induced bronchoconstriction test, aerobic fitness (cardiopulmonary exercise test), muscle strength and functionality (timed up and go; timed up and down stairs) were evaluated. RESULTS: Seventy-one patients with asthma (mean age 11.5 ± 2.7) and 71 healthy subjects (mean age 10.7 ± 2.5) were included. All asthmatic children had mild to moderate and stable asthma. EIB occurred in 56.3% of asthmatic children. Lung function was significantly (p < .05) lower in the asthmatic group when compared to healthy peers, as well as the cardiorespiratory fitness, muscle strength, lifestyle and functionality. Moreover, asthmatic children were more likely to have atopic dermatitis, allergic reactions, food allergies, and a family history of asthma when compared to healthy children. CONCLUSIONS: Children with mild-to-moderate asthma presenting exercise symptoms show a reduction in cardiorespiratory fitness, muscle strength, lung function, functionality, and lifestyle when compared to healthy peers. The study provides data for pediatricians to support exercise practice aiming to improve prognosis and quality of life in asthmatic children.

Tailored Exercise during Hematopoietic Stem Cell Transplantation Hospitalization in Children with Cancer: A Prospective Cohort Study.

We assessed the clinical effects of a supervised exercise (aerobic + resistance) intervention performed during inpatient hospitalization for pediatric hematopoietic stem cell transplantation (HSCT). Patients were placed in an exercise (n = 65 (47 and 18 with allogeneic (allo-) and autologous (auto-) HSCT, respectively)) or a control (n = 53 (39 and 14)) group. Exercise interventions were performed in isolated hospital patient rooms. Patients were followed-up from the beginning of the conditioning phase up to 6 years. We assessed survival, risk of graft-versus-host disease (GvHD) or graft failure (primary outcomes), and engraftment kinetics, supportive care, toxicity profile, and immune reconstitution for auto-HSCT and allo-HSCT. The exercise intervention was safe and did not affect the risk of mortality, acute/chronic GvHD, or graft failure (all p > 0.05). No between-group differences (p > 0.05) were found for the remainder of clinical endpoints, except for a reduced number of total and viral infections in the exercise group after allo-HSCT (unadjusted p = 0.005 for both total and viral infections, and adjusted p = 0.023 and 0.083, respectively). In conclusion, exercise performed during inpatient hospitalization for pediatric HSCT is safe and well tolerated during both auto and allo-HSCT and tends to decrease the risk of infection after allo-HSCT. These findings provide additional support to the notion that a multidisciplinary approach (i.e., including the work of exercise specialists) is suitable in the management of children undergoing HSCT. Further studies are needed to determine whether applying a different training stimulus (notably, higher exercise intensities) exerts positive effects on HSCT prognosis in these patients.

Effect of a combined exercise program on physical fitness, lung function, and quality of life in patients with controlled asthma and exercise symptoms: A randomized controlled trial.

BACKGROUND: Asthmatic patients may benefit from exercise training, although the effects of a combined aerobic and resistance training program are still poorly investigated in children and adolescents. OBJECTIVE: To analyze the effects of a combined exercise training (resistance and aerobic) program on aerobic fitness, lung function, asthma control and quality of life in a group of mild-moderate asthmatic children with exercise symptoms. METHODS: This was a 12-week randomized controlled trial including children and adolescents diagnosed with mild-moderate asthma and presenting exercise-induced symptoms. The intervention group (IG) performed the exercise training (resistance and aerobic) 3 days/week, for 60 minutes. The control group (CG) followed routine clinical orientations. The main outcomes were cardiorespiratory fitness, muscle strength, lung function, quality of life, asthma control, and functional tests after 3 months of the intervention. RESULTS: Fifty-three patients (IG = 25 and CG = 28) with a mean age of 11.5 ± 2.6 years were included. No significant differences were found between groups regarding lung function, asthma control, quality of life, and functional tests. Ventilatory equivalent for oxygen consumption at ventilatory threshold (P = .025; ηp2 = 0.083), peak oxygen consumption (P = .008; ηp2 = 0.116) and test duration (P = .014; ηp2 = 0.1) presented greater improvements in the IG. In addition, improvements were observed in leg press (P < .001; ηp2 = 0.36), hamstring curl (P = .001; ηp2 = 0.217), high row (P = .003; ηp2 = .167), low row (P = .009; ηp2 = 0.128) and quadriceps leg extension (P = .015; ηp2 = 0.108) in the IG. CONCLUSION: Combined exercise training (resistance and aerobic) improved cardiorespiratory fitness and muscle strength in children and adolescents with controlled asthma and exercise symptoms.

Inhospital exercise benefits in childhood cancer: A prospective cohort study.

Childhood cancer patients are at risk of developing important adverse effects, mortality and disease relapse after treatments, which has a substantial economic impact on healthcare systems. The objective of this study was to determine the effects of supervised inhospital exercise on clinical endpoints during childhood cancer treatment. 169 children with a new diagnosis of cancer were divided into an exercise intervention (n = 68, 11 ± 4 years) or a control group (n = 101, 11 ± 3 years). The cohort was followed up from the start of treatment for up to five years. Supervised inhospital exercise intervention was performed during the neoadjuvant (for solid tumors) or intensive chemotherapy treatment period (for leukemias). The median duration of the intervention was 22 (interquartile range, 14-28) weeks. We assessed survival, risk of disease relapse or metastasis, and days of hospitalization (primary outcomes), and cardiovascular function, anthropometry and blood variables (secondary outcomes). No exercise-related adverse events were noted. The exercise group had significantly less days of hospitalization than the control group (P = .031), resulting in a lower (~-17%) mean total economic cost of hospitalization in the former. Moreover, echocardiography-determined left ventricular function (ejection fraction and fractional shortening) was significantly impaired in the control group after treatment compared with baseline, whereas it was maintained in the exercise group (P = .024 and .021 for the between-group differences, respectively). In conclusion, supervised inhospital exercise intervention is safe and plays a cardioprotective role, at least in the short term, in children with cancer, also reducing hospitalization time, and therefore alleviating the economic burden.

Inhospital Exercise Training in Children With Cancer: Does It Work for All?

Purpose: Physical exercise training might counteract the weakening effects of both pediatric cancer and anti-cancer treatment. We aimed to analyze the prevalence of "responders" and "non-responders" to inhospital exercise training in children with cancer and to identify the factors that could influence responsiveness, which might help personalize exercise interventions for this patient population. Methods: We performed an ancillary analysis of the randomized controlled trial "Physical activity in Pediatric Cancer" (NCT01645436), in which 49 children with solid tumors were allocated to an inhospital exercise intervention or control group. The present study focused on the children in the former group (n = 24, 10 ± 4 years), who performed 3 weekly training sessions (aerobic + strength exercises). The intervention lasted 19 ± 8 weeks (i.e., from the start to the end of neoadjuvant chemotherapy treatment). A responder-vs-non-responder analysis was performed for physical capacity-related endpoints (five-repetition maximum strength, functional mobility tests, and cardiorespiratory fitness [CRF]). Only those participants showing improvements in a given test of a magnitude greater than both the random error and the threshold for clinically meaningful changes were considered responders. Results: Most participants improved their performance in the strength tests, with 80, 88, and 93% of total showing a positive response for seated bench press, lateral row, and leg press, respectively (p < 0.001). No significant improvements were observed for the functional mobility tests or CRF (p > 0.05, rate of responsiveness ≤ 50%). No differences between responders and non-responders were observed for sex, age, type of cancer, or treatment (i.e., including or not anthracyclines/radiotherapy). However, significant differences (p < 0.05) were observed between responders and non-responders for baseline performance in all the tests, and a significant (p < 0.05) inverse relationship was found between baseline performance and relative improvement for most endpoints. Conclusions: Although most children improved their muscle strength after the exercise intervention, a considerable individual variability was observed for the training responsiveness of functional mobility and CRF. A lower baseline performance was associated with a higher responsiveness for all the study endpoints, with the fittest children at the start of treatment showing the lowest responses. Efforts to individualize exercise prescription are needed to maximize responsiveness in pediatric cancer patients.

Effects of Exercise on the Immune Function of Pediatric Patients With Solid Tumors: Insights From the PAPEC Randomized Trial.

The purpose of this study was to assess the effects of an in-hospital exercise intervention during neoadjuvant chemotherapy on the inflammatory profile and immune cell subpopulation in 20 children with solid tumors (control [n = 11] and exercise group [n = 9]). Although no significant interaction (group × time) effect was found with an analysis of variance test, we found a trend toward an interaction effect for natural killer cells expressing the immunoglobulin-like receptor KIR2DS4, with their numbers remaining stable in the exercise group but increasing in controls. Our data support that exercise interventions are safe in pediatric cancer patients with solid tumors during chemotherapy treatment despite its aggressive, immunosuppressive nature.

Exercise Intervention in Pediatric Patients with Solid Tumors: The Physical Activity in Pediatric Cancer Trial.

INTRODUCTION: The randomized controlled trial "Physical Activity in Pediatric Cancer" determined the effects of an inhospital exercise intervention combining aerobic and muscle strength training on pediatric cancer patients with solid tumors undergoing neoadjuvant chemotherapy. METHODS: Participants were allocated to an exercise (n = 24, 17 boys; mean ± SEM age, 10 ± 1 yr) or control group (n = 25, 18 boys; 11 ± 1 yr). Training included three sessions per week for 19 ± 2 wk. Participants were assessed at treatment initiation, termination, and 2 months after end treatment. The primary endpoint was muscle strength (as assessed by upper and lower-body five-repetition-maximum tests). Secondary endpoints included cardiorespiratory fitness, functional capacity during daily life activities, physical activity, body mass and body mass index, and quality of life. RESULTS: Most sessions were performed in the hospital's gymnasium. Adherence to the program averaged 68% ± 4% and no major adverse events or health issues were noted. A significant interaction (group-time) effect was found for all five-repetition maximum tests (leg/bench press and lateral row; all P < 0.001). Performance significantly increased after training (leg press: 40% [95% confidence interval [CI], 15-41 kg); bench press: 24% [95% CI, 6-14 kg]; lateral row 25% [95% CI, 6-15 kg]), whereas an opposite trend was found in controls. Two-month post values tended to be higher than baseline for leg (P = 0.017) and bench press (P = 0.014). In contrast, no significant interaction effect was found for any of the secondary endpoints. CONCLUSION: An inhospital exercise program for pediatric cancer patients with solid tumors undergoing neoadjuvant treatment increases muscle strength despite the aggressiveness of such therapy.

Physical-capacity-related genetic polymorphisms in children with cystic fibrosis.

In patients with cystic fibrosis (CF), physical capacity (PC) has been correlated with mortality risk. In turn, PC is dependent on genetic factors. This study examines several polymorphisms associated with PC and health-related phenotype traits (VO2peak, FEV1, FVC, PImax and muscular strength) in a group of children with CF (n = 66, primary purpose). The same analyses were also performed in a control group of healthy children (n = 113, secondary purpose). The polymorphisms determined were classified as muscle function polymorphisms (ACE rs1799752; AGT rs699; ACTN3 rs1815739; PTK2 rs7843014 and rs7460; MSTN rs1805086; TRHR rs7832552; NOS3 rs2070744) or energy metabolism polymorphisms (PPARGC1A rs8192678; NRF1 rs6949152; NRF2 rs12594956; TFAM rs1937; PPARD rs2267668; ACSL1 rs6552828). No significant polymorphism/phenotype correlations were detected in children with CF, with marginal associations being observed between NOS3 rs2070744 and VO2peak and FEV1, as well as between PPARGC1A rs8192678 and FEV1. Overall, similar findings were observed in the control group, i.e., no major associations. The PC-related polymorphisms examined seem to have no effects on the PC or health of children with CF.

Levels of moderate--vigorous physical activity are low in Spanish children with cystic fibrosis: a comparison with healthy controls.

BACKGROUND: Physical activity (PA) is recommended as part of the treatment regimen for cystic fibrosis (CF) although objective methods have been scarcely used to monitor achievement of PA guidelines. METHODS: PA was measured by accelerometer in outpatient CF children (n=47) and results were compared with those obtained in age- and gender-matched healthy controls (n=39). RESULTS: 2.1% of the outpatients fulfilled PA guidelines (i.e. ≥60min·day(-1) of moderate-to-vigorous PA (MVPA)) vs. 34.2% of controls. Overall, lower MVPA levels were observed in CF patients than controls despite the former undergoing more light or total PA. Peak oxygen uptake was also lower in the CF group than in controls (37.5±7.8 vs. 43.5±7.6ml·kg(-1)·min(-1), p=0.002) and was correlated with MVPA and vigorous PA in the former. CONCLUSIONS: These findings support a need to promote PA interventions (including MVPA) targeted at improving cardiorespiratory fitness in CF children.

Benefits of combining inspiratory muscle with 'whole muscle' training in children with cystic fibrosis: a randomised controlled trial.

BACKGROUND: The purpose of this study (randomised controlled trial) was to assess the effects of an 8-week combined 'whole muscle' (resistance+aerobic) and inspiratory muscle training (IMT) on lung volume, inspiratory muscle strength (PImax) and cardiorespiratory fitness (VO2 peak) (primary outcomes), and dynamic muscle strength, body composition and quality of life in paediatric outpatients with CF (cystic fibrosis, secondary outcomes). We also determined the effects of a detraining period. METHODS: Participants were randomly allocated with a block on gender to a control (standard therapy) or intervention group (initial n=10 (6 boys) in each group; age 10±1 and 11±1 years). The latter group performed a combined programme (IMT (2 sessions/day) and aerobic+strength exercises (3 days/week, in-hospital)) that was followed by a 4-week detraining period. All participants were evaluated at baseline, post-training and detraining. RESULTS: Adherence to the training programme averaged 97.5%±1.7%. There was a significant interaction (group×time) effect for PImax, VO2peak and five-repetition maximum strength (leg-press, bench-press, seated-row) (all (p<0.001), and also for %fat (p<0.023) and %fat-free mass (p=0.001), with training exerting a significant beneficial effect only in the intervention group, which was maintained after detraining for PImax and leg-press. CONCLUSION: The relatively short-term (8-week) training programme used here induced significant benefits in important health phenotypes of paediatric patients with CF. IMT is an easily applicable intervention that could be included, together with supervised exercise training in the standard care of these patients.

Aerobic fitness is associated with lower risk of hospitalization in children with cystic fibrosis.

BACKGROUND: Children with cystic fibrosis (CF) often have to be hospitalized because of acute exacerbation of their respiratory symptoms. Given the fact that improved peak oxygen uptake (VO2peak ) is positively associated with lung function and overall health in children with CF, this study examined the association between VO2peak and the need for hospitalization in a cohort of pediatric CF patients. METHODS: In a 3-year study, 77 CF children with mild-to-moderately severe CF (forced expiratory volume in 1 sec [FEV1 ] ≥ 50%) underwent a maximal exercise test to determine VO2peak . Anthropometric, lung function and muscle strength measurements were also conducted and dates of hospitalization were recorded for the study period. Associations were then determined between the variables recorded and hospitalization by univariate and multivariate Cox proportional hazards regression analyses. RESULTS: VO2peak was 38.6 ± 6.7 ml kg(-1) min(-1) for boys and 31.9 ± 6.9 ml kg(-1) min(-1) for girls. In multivariate analyses, VO2peak was the only variable significantly associated with time to hospitalization (hazard ratio 0.91, P = 0.03). CONCLUSION: A significant association was detected between greater aerobic fitness, and lower risk of hospitalization. Because hospitalization due to respiratory exacerbation is a powerful prognostic factor, our findings provide further support for the importance of aerobic fitness evaluation in the management of children with mild-to-moderately severe CF.

Physical Activity in Pediatric Cancer patients with solid tumors (PAPEC): trial rationale and design.

BACKGROUND: This randomized controlled trial on Physical Activity in Pediatric Cancer (PAPEC) was designed to assess the impact of an exercise program on pediatric cancer patients undergoing chemotherapy for solid tumors. METHODS AND DESIGN: 60 pediatric patients of both sexes, aged 4 to 18 years and undergoing treatment for extracranial primary solid tumors will be recruited for this trial. Each participant will be randomly assigned (with blocking on sex) to either an intervention or control (normal care) group. The intervention group will participate in combined inpatient physical training (aerobic + strength) for the duration of neoadjuvant chemotherapy. The intervention will include 3 weekly 60-70 min exercise sessions in the child's room or in a pediatric gym at the hospital, depending on the child's health state. In both groups, determination of several primary (cardio-respiratory fitness, muscle strength, functional capacity, physical activity levels, body weight and quality of life) and secondary outcomes [immune function and inflammatory profile (blood levels of 47 cytokines)] will be made at the following time points: (i) before the exercise intervention (immediately after diagnosis and before treatment onset); (ii) after the exercise intervention (upon termination of neoadjuvant chemotherapy); and (iii) after a detraining period (2 months after the intervention). DISCUSSION: The PAPEC trial will provide relevant new information on biological mechanisms and inform on the potential clinical use of exercise during pediatric cancer treatment as a simple way to prevent future long-term treatment effects and improve the general health state of pediatric cancer patients.

Intrahospital weight and aerobic training in children with cystic fibrosis: a randomized controlled trial.

PURPOSE: The purpose of our study was to assess the effects of an 8-wk intrahospital combined circuit weight and aerobic training program performed by children with cystic fibrosis (of low-moderate severity and stable clinical condition) on the following outcomes: cardiorespiratory fitness (VO2peak) and muscle strength (five-repetition maximum (5RM) bench press, 5RM leg press, and 5RM seated row) (primary outcomes) and pulmonary function (forced vital capacity, forced expiratory volume in 1 s), weight, body composition, functional mobility (Timed Up and Down Stairs and 3-m Timed Up and Go tests), and quality of life (secondary outcomes). We also determined the effects of a detraining period (4 wk) on the aforementioned outcomes. METHODS: We performed a randomized controlled trial design. Eleven participants in each group (controls: 7 boys, age = 11 ± 3 yr, body mass index = 17.2 ± 0.8 kg · m(-2) (mean ± SEM); intervention: 6 boys, age = 10 ± 2 yr, body mass index = 18.4 ± 1.0 kg · m(-2)) started the study. RESULTS: Adherence to training averaged 95.1% ± 7.4%. We observed a significant group × time interaction effect (P = 0.036) for VO2peak. In the intervention group, VO2peak significantly increased with training by 3.9 mL · kg(-1) · min(-1) (95% confidence interval = 1.8-6.1 mL · kg(-1) · min(-1), P = 0.002), whereas it decreased during the detraining period (-3.4 mL · kg(-1) · min(-1), 95% confidence interval = -5.7 to -1.7 mL · kg(-1) · min(-1), P = 0.001). In contrast, no significant changes were observed during the study period within the control group. Although significant improvements were also observed after training for all 5RM strength tests (P < 0.001 for the interaction effect), the training improvements were not significantly decreased after the detraining period in the intervention group (all P > 0.1 for after training vs detraining). We found no significant training benefits in any of the secondary outcomes. CONCLUSIONS: A short-term combined circuit weight and aerobic training program performed in a hospital setting induces significant benefits in the cardiorespiratory fitness and muscle strength of children with cystic fibrosis.

Does resistance training improve the functional capacity and well being of very young anorexic patients? A randomized controlled trial.

PURPOSE: We determined the effects of a 3-month low-moderate-intensity strength training program (2 sessions/week) on functional capacity, muscular strength, body composition, and quality of life (QOL) in 22 young (12-16 yrs) anorexic outpatients. METHODS: Patients were randomly assigned to a training or control group (n=11 [10 females] each). Training sessions were of low intensity (loads for large muscle groups ranging between 20%-30% and 50%-60% of six repetitions maximum [6RM] at the end of the program). We measured functional capacity by the time up and go and the timed up and down stairs tests. Muscular strength was assessed by 6RM measures for seated bench and leg presses. We estimated percent body fat and muscle mass. We assessed patients' QOL with the Short Form-36 items. RESULTS: The intervention was well tolerated and did not have any deleterious effect on patients' health, and did not induce significant losses in their body mass. The only studied variable for which a significant interaction (group x time) effect was found (p=.009) was the 6RM seated lateral row test. CONCLUSIONS: Low-moderate-intensity strength training does not seem to add major benefits to conventional psychotherapy and refeeding treatments in young anorexic patients.

Exercise during hematopoietic stem cell transplant hospitalization in children.

PURPOSE: The purpose of this controlled trial was to assess the effect of an approximately 3-wk intrahospital exercise intervention performed during inpatient hospitalization for pediatric allogeneic hematopoietic stem cell transplant (HSCT) on (i) immune cell recovery and (ii) body composition. METHODS: Immune (i.e., blood counts of leukocytes, monocytes, lymphocytes, and lymphocyte subpopulations) and anthropometric variables (i.e., body mass, body mass index, and estimated fat-free mass) were measured before and after (+15 and 30 d) HSCT. Seven children (5 boys and 2 girls; age (mean +/- SD) = 8 +/- 4 yr) with high-risk cancer performed an individualized training program (aerobic + resistance exercises) in their isolated hospital rooms. We also assessed a control group (n = 13; 9 boys and 4 girls; age = 7 +/- 3 yr) with similar medical conditions and following the same transplant protocol. RESULTS: In both groups, the dendritic cell count decreased from pre-HSCT to +15 d post-HSCT and thereafter (up to +30 d) remained stabile; however, the posttransplant decrease was more abrupt in the control group than that in the intervention group (-87% vs -63%, respectively, from pre-HSCT to +15 d). The rest of the immune cell parameters measured showed a similar response from pre-HSCT to post-HSCT in both groups. We found a significant effect of the interaction group x time for all anthropometric variables (weight, body mass index, body fat, and fat-free mass), indicating an increase over the hospitalization period only in the intervention group, for example, body mass increased from 32.9 +/- 18.7 kg pre-HSCT to 35.4 +/- 18.6 kg at +30 d in the intervention group versus a decrease from 30.2 +/- 16.6 to 29.3 +/- 6.3 kg in the control group. CONCLUSION: Our findings support the feasibility of exercise training interventions during hospitalization, including immunocompromised children.