Two protocols to measure mitochondrial capacity in women and adolescent girls: a 31P-MRS preliminary study.

The phosphocreatine (PCr) recovery time constant (τ) following exercise provides a measure of mitochondrial oxidative capacity. The purpose of this investigation was to use 2 different protocols to determine τ in adolescent females. 31P-MR spectra were collected during 2 exercise tests in 6 adolescent girls (13.8 ± 0.3 y) and 7 women (23.2 ± 3.4 y). The first test consisted of 23 repeated 4 seconds maximal isometric calf contractions separated by 12-second recovery; PCr recovery between the final 18 contractions was used to calculate τ. The second test was a sustained 20-second maximal contraction; recovery was fitted with an exponential function to measure τ. PCr τ did not significantly differ between groups: (gated exercise: 4 girls: 16 ± 5 s, 7 women: 17 ± 5 s, p; sustained exercise: 6 girls: 19 ± 6 s, 7 women: 19 ± 4 s). Bland-Altman analysis demonstrated a close agreement between sustained and gated exercise. Both gated and sustained exercise appear feasible in a pediatric population, and offer a noninvasive evaluation of mitochondrial oxidative capacity.

The effect of ivacaftor in adolescents with cystic fibrosis (G551D mutation): an exercise physiology perspective.

PURPOSE: The purpose of this report was to evaluate the influence of 12 weeks of ivacaftor treatment on the aerobic function of 2 teenage patients with cystic fibrosis (CF; ΔF508/G551D) using a maximal cardiopulmonary exercise test. SUMMARY OF KEY POINTS: One patient, with relatively mild disease, demonstrated no clinically meaningful changes in maximal oxygen uptake ((Equation is included in full-text article.)O2max). However, in the second case, with more established lung disease on imaging, (Equation is included in full-text article.)O2max improved by approximately 30%, an improvement out of proportion with early lung function changes. This improvement resulted from increased muscle oxygen delivery and extraction. STATEMENT OF CONCLUSIONS: Cardiopulmonary exercise testing can monitor the extent and cause(s) of change following interventions such as ivacaftor, with the potential to identify functional changes independent from spirometry indices. RECOMMENDATIONS FOR CLINICAL PRACTICE: Cardiopulmonary exercise testing represents an important and comprehensive clinical assessment tool, and its use as an outcome measure in the functional assessment of patients with CF is encouraged.

Skeletal muscle contributions to reduced fitness in cystic fibrosis youth.

Background: Increased maximal oxygen uptake (V̇O2max) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle "quality") and skeletal muscle size (muscle "quantity") are both proposed as potential causes for the lower V̇O2max, although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O2max to address this "quality" vs. "quantity" debate. Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size - muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t-tests and effect sizes (ES) identified differences between groups in V̇O2max, once mCSA and TMV were controlled for. Results: V̇O2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45). Conclusions: A lower V̇O2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle "quality" in CF (as muscle "quantity" is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

Quantification of thigh muscle volume in children and adolescents using magnetic resonance imaging.

Abstract Estimating muscle volume (MV) using variable numbers of cross-sectional area (CSA) slices obtained from magnetic resonance imaging (MRI) introduces an error that is known in adults, but not in children and adolescents, whereby body sizes differ due to growth and maturation. Therefore, 15 children and adolescents (11 males, 14.8 ± 2.1 years) underwent MRI scans of the right thigh using a 1.5 T scanner to establish this error. A criterion MV was determined by tracing around and summing all CSAs, with MV subsequently estimated using every second, third, fourth and fifth CSA slice. Bland-Altman plots identified mean bias and limits of agreement (LoA) between methods. Error rates between 1.0 and 10.4% were seen between criterion and estimated MV. Additional analyses identified an impact of formulae selection, with a cylindrical formula preferred to a truncated cone. To counter high error between criterion and estimated MV due to the discrepancies in the number of CSA slices analysed, length-matched criterion volumes were established, with reduced error rates (0.5-2.0%) being produced as a result. CSA at 50% thigh-length also predicted MV, producing a high error (13.8-39.6%). Pearson's correlation coefficients determined relationships between error and measures of body size/composition, with all body size/composition measures being correlated (r = -0.78-0.86, p < 0.05) with the error between criterion and estimated MV. To conclude, MV can be accurately estimated using fewer CSA slices. However, the associated error must be considered when calculating MV in children and adolescents, as body size biases estimates.

Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.

PURPOSE: The aim of this study was to describe the relationship between body size and oxygen uptake efficiency slope (OUES) in pediatric patients with cystic fibrosis (CF) and healthy controls (CON), to identify appropriate scaling procedures to adjust the influence of body size upon OUES. METHODS: The OUES was derived using maximal and submaximal points from cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body mass (BM), and body surface area (BSA) using ratio-standard (Y/X) and allometric (Y/X) methods. Pearson's correlation coefficients were used to determine the relationship between body size and OUES. RESULTS: When scaled using the ratio-standard method, OUES had a significant positive relationship with stature (r = 0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric exponents (b) for CF and CON were stature 3.00, BM 0.86, and BSA 1.40. A significant negative correlation was found between OUES and stature in the CF group when scaled allometrically (r = -0.37, P = 0.027). Nonsignificant (P > 0.05) correlations for the whole group were found between OUES and allometrically scaled BM (CF r = -0.25, CON, r = 0.15) and BSA (CF r = -0.27, CON r = 0.13). CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard scaling, successfully eliminates the influence of body size upon OUES. Therefore, this enables a more direct comparison of the OUES between patients with CF and healthy controls.

Is cardiac autonomic function associated with cardiorespiratory fitness and physical activity in children and adolescents? A systematic review of cross-sectional studies.

BACKGROUND: Heart rate variability (HRV) is considered to explain improvements in cardiovascular health accrued by physical activity (PA) and cardiorespiratory fitness (CRF) over and above traditional cardiovascular risk factors. OBJECTIVE: To systematically address associations between HRV, PA and CRF in children and adolescents. DATA SOURCES: Medline, EMBASE, SportDISCUS and CINAHL Plus were searched on 5th September 2015 and updated on 4th August 2016. ELIGIBILITY CRITERIA: Observational studies comparing HRV in different groups of PA and CRF, and/or studies investigating associations between PA, CRF and HRV. Sports practices and PA intensities were also included. The square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), the spectral density in the high (HF) and low (LF) frequency, and the LF/HF ratio were included. Risk of bias was assessed using the adapted Newcastle-Ottawa Scale (NOS). RESULTS: Heterogeneity exists in the assessment of the exposures and outcomes, and sample characteristics. Risk of bias (NOS) was observed in most of the studies. Studies with low risk of bias showed positive associations between moderate-to-vigorous PA and RMSSD. The evidence for the associations between PA and frequency indices is weak. Similarly, the evidence for the association between CRF and HRV is weak. CONCLUSIONS: Despite the heterogeneity in the studies, moderate-to-vigorous PA is positively associated with RMSSD, but less clear are the associations between CRF and HRV, as well as other PA intensities. Further research is needed to clarify the role of PA and CRF on HRV in children and adolescents.

Impaired Pulmonary V˙O2 Kinetics in Cystic Fibrosis Depend on Exercise Intensity.

PURPOSE: This study aimed to investigate the effects of mild-to-moderate cystic fibrosis (CF) on the pulmonary oxygen uptake (V˙O2) kinetics of seven pediatric patients (13.5 ± 2.8 yr) versus seven healthy matched controls (CON; 13.6 ± 2.4 yr). We hypothesized that CF would slow the V˙O2 kinetic response at the onset of moderate (MOD) and very heavy (VH) intensity cycling. METHODS: Changes in breath-by-breath V˙O2, near-infrared spectroscopy-derived muscle deoxygenation ([HHb]) at the vastus lateralis muscle and thoracic bioelectrical impedance-derived heart rate (HR), stroke volume index, and cardiac index were measured during repeat transitions to MOD (90% of the gas exchange threshold) and VH (Δ60%) intensity cycling exercise. RESULTS: During MOD, the phase II V˙O2 τ (P = 0.84, effect size [ES] = 0.11) and the overall mean response time (MRT) (P = 0.52, ES = 0.11) were not significantly slower in CF versus CON. However, during VH exercise, the phase II V˙O2 τ (P = 0.02, ES = 1.28) and MRT (P = 0.01, ES = 1.40) were significantly slower in CF. Cardiac function, central O2 delivery (stroke volume index and cardiac index), and muscle [HHb] kinetics were unaltered in CF. However, the arteriovenous O2 content difference ((Equation is included in full-text article.)) was reduced during VH at 30 s (P = 0.03, ES = 0.37), with a trend for reduced levels at 0 s (P = 0.07, ES = 0.25), 60 s (P = 0.05, ES = 0.28), and 120 s (P = 0.07, ES = 0.25) in CF. Furthermore, (Equation is included in full-text article.)significantly correlated with the VH phase II V˙O2 τ (r = -0.85, P = 0.02) and MRT (r = -0.79, P = 0.03) in CF only. CONCLUSION: Impairments in muscle oxidative metabolism during constant work rate exercise are intensity dependent in young people with mild-to-moderate CF. Specifically, V˙O2 kinetics are slowed during VH but not MOD cycling and appear to be mechanistically linked to impaired muscle O2 extraction and utilization.

Impaired aerobic function in patients with cystic fibrosis during ramp exercise.

PURPOSE: This study aimed to document the matching of muscle O2 delivery to O2 use in young patients with cystic fibrosis (CF) from muscle deoxygenation (HHb) dynamics during ramp exercise. METHODS: Ten patients with stable, mild-to-moderate CF (12.7 ± 2.8 yr) and 10 healthy controls (CON, 12.8 ± 2.8 yr) completed a combined ramp and supramaximal cycling test to determine maximal O2 uptake (V˙O2max). Changes in gas exchange and ventilation, HR, and m. vastus lateralis HHb (near-infrared spectroscopy) were assessed. Δ[HHb]-work rate and Δ[HHb]-V˙O2 profiles were normalized and fit using a sigmoid function. RESULTS: Aerobic function was impaired in CF, indicated by very likely reduced fat-free mass-normalized V˙O2max (mean difference, ±90% confidence interval: -7.9 mL·kg·min, ±6.1), very likely lower V˙O2 gain (-1.44 mL·min·W, ±1.12), and a likely slower V˙O2 mean response time (11 s, ±13). An unclear effect was found upon the absolute and relative work rate (-14 W, ±44, and -0.7% peak power output, ±12.0, respectively) and the absolute and percentage (-0.10 L·min, ±0.43, and 3.3% V˙O2max, ±6.0) V˙O2 corresponding to 50% Δ[HHb] amplitude, respectively, between groups. However, arterial oxygen saturation (SpO2) was very likely lower in CF (-1%, ±1) and demonstrated moderate-to-very large relations with parameters of aerobic function. CONCLUSIONS: Young patients with mild-to-moderate CF present with impaired aerobic function during ramp incremental cycling exercise. Because the rate of fractional O2 extraction during ramp cycling exercise was not altered by CF, yet SpO2 was lower, the present findings support the notion of centrally mediated oxygen delivery to principally limit the aerobic function of pediatric patients with CF during ramp incremental cycling exercise.