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.

Survey of exercise testing and training in cystic fibrosis clinics in the UK: a decade of progress.

OBJECTIVES: Regular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training for pwCF in the UK was conducted over a decade ago. With the landscape of CF changing considerably during this time, this survey aimed to evaluate UK-based exercise testing and training practices for pwCF a decade on. DESIGN: Cross-sectional, online survey. PARTICIPANTS: A survey was distributed electronically to UK CF clinics and completed by the individual primarily responsible for exercise services. Descriptive statistics and qualitative analyses were undertaken. RESULTS: In total, 31 CF centres participated, representing ~50% of UK specialist clinics. Of these, 94% reported using exercise testing, 48% of which primarily use cardiopulmonary exercise testing. Exercise testing mostly occurs at annual review (93%) and is most often conducted by physiotherapists (62%). A wide variation in protocols, exercise modalities, normative reference values and cut-offs for exercise-induced desaturation are currently used. All centres reportedly discuss exercise training with pwCF; 94% at every clinic appointment. However, only 52% of centres reportedly use exercise testing to inform individualised exercise training. Physiotherapists typically lead discussions around exercise training (74%). CONCLUSIONS: These data demonstrate that the majority of respondent centres in the UK now offer some exercise testing and training advice for pwCF, representing a marked improvement over the past decade. However, continued efforts are now needed to standardise exercise practices, particularly regarding field testing practices and the translation of test results into personalised training programmes for pwCF.

Web-based physical activity promotion in young people with CF: a randomised controlled trial.

BACKGROUND: Physical activity levels are known to decline following hospitalisation for people with cystic fibrosis (pwCF). However, optimal physical activity promotion strategies are unclear. This study investigated the effect of a web-based application (ActivOnline) in promoting physical activity in young pwCF. METHODS: Multicentre randomised controlled trial with assessor blinding and qualitative evaluation. People with CF (12-35 years) admitted to hospital for a respiratory cause were eligible and randomised to the 12-week ActivOnline intervention (AO) or usual care (UC). The primary outcome was change in device-based time spent in moderate-to-vigorous physical activity (MVPA) from baseline to post-intervention. Follow-up was at 6 months from hospital discharge when qualitative evaluation was undertaken. RESULTS: 107 participants were randomised to AO (n=52) or UC (n=55). Sixty-three participants (59%) contributed to the intention-to-treat analysis. Mean (SD) age was 21 (6) years (n=46, <18 years). At baseline, physical activity levels were high in both groups (AO 102 (52) vs UC 127 (73) min/day). There was no statistically significant difference in MVPA between groups at either timepoint (post-intervention mean difference (95% CI) -14 mins (-45 to 16)). Uptake of the intervention was low with only 40% (n=21) of participants accessing the web application. CONCLUSION: A web-based application, including individualised goal setting, real-time feedback and motivation for behavioural change, was no better than usual care at promoting physical activity in young pwCF following hospital discharge. High levels of baseline physical activity levels in both groups, and limited engagement with the intervention, suggest alternative strategies may be necessary to identify and support young pwCF who would benefit from enhanced physical activity. TRIAL REGISTRATION NUMBER: ACTRN12617001009303, 13 July 13 2017.

Barriers and facilitators to physical activity among children, adolescents, and young adults with cystic fibrosis: a systematic review and thematic synthesis of qualitative research.

OBJECTIVES: Physical activity is widely recommended in the treatment and management of cystic fibrosis (CF). Despite the numerous physical and psychological benefits, many young people with CF are not achieving the recommended levels of physical activity. The aim of this systematic review was to identify and synthesise available qualitative investigations exploring the motives for, barriers to and facilitators of physical activity among young people with CF. METHODS: The following six electronic databases were systematically searched: Applied Social Sciences Index and Abstracts (ASSIA), CINAH, EMBASE, MEDLINE, MEDLINE-in-process, PsycINFO up to August 2019. Keywords were used to identify qualitative research that explored engagement in physical activity among young people with CF. Titles and abstracts were screened by two independent reviewers, and potentially relevant articles were retrieved in full. Articles were eligible for inclusion if they employed any qualitative method and recruited participants under the age of 24 years with CF. Risk of bias of included studies was assessed via the Critical Appraisal Skills Programme. Results were synthesised using a thematic approach. RESULTS: Seven studies met our inclusion criteria and were included in the review. Overall, studies were of moderate to high quality. Thematic synthesis identified nine main themes that encompass motives for, barriers to and facilitators of physical activity among young people with CF. These were (1) Perceptions of physical activity. (2) Value attributed to physical activity. (3) Social influences. (4) Competing priorities. (5) Fluctuating health. (6) Normality. (7) Control beliefs. (8) Coping strategies. (9) Availability of facilities. Previous reviews have been unable to identify intervention characteristics that influence physical activity behaviour. CONCLUSIONS: This review provides detailed information on the physical (biological-clinical), psychological, social and environmental influences on physical activity behaviour, thus providing numerous targets for future interventions. This in turn could facilitate promotion of physical activity among young people with CF.

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.

Enhancing intrinsic motivation for physical activity among adolescents with cystic fibrosis: a qualitative study of the views of healthcare professionals.

OBJECTIVE: To explore the views of healthcare professionals from cystic fibrosis (CF) multidisciplinary teams (MDT) on physical activity for adolescents with CF, the specific strategies used for physical activity promotion and associated challenges. DESIGN: In this exploratory study, in-depth qualitative interviews were conducted with 15 healthcare professionals from CF MDTs to explore their views surrounding physical activity promotion for adolescents with CF. PARTICIPANTS: Eleven physiotherapists (nine female), two consultants (both male) and two dieticians (both female) provided written informed consent and participated in the study. SETTING: CF clinics in the UK. RESULTS: While healthcare professionals highlighted the importance of physical activity in the management of CF, they noted that very few patients were motivated solely by (CF or general) health reasons. Healthcare professionals discussed the need for physical activity to be an enjoyable and routine part of their life, undertaken with significant others, outside the clinic whenever possible. Adopted approaches for physical activity promotion focused on providing individualised recommendations that suit the patients' individual needs and goals and enhance intrinsic motivation for physical activity. CONCLUSION: Our research offers valuable information for those seeking to develop interventions to promote physical activity among adolescents with CF. Specifically, intervention developers should focus on developing individualised interventions that focus on enhancing intrinsic motivation and support the integration of physical activity into everyday life.

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.

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.

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.

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.

Systematic review and meta-analysis of the association between childhood overweight and obesity and primary school diet and physical activity policies.

Obesity is a major public health concern and there are increasing calls for policy intervention. As obesity and the related health conditions develop during childhood, schools are being seen as important locations for obesity prevention, including multifaceted interventions incorporating policy elements. The objective of this systematic review was to evaluate the effects of policies related to diet and physical activity in schools, either alone, or as part of an intervention programme on the weight status of children aged 4 to 11 years. A comprehensive and systematic search of medical, education, exercise science, and social science databases identified 21 studies which met the inclusion criteria. There were no date, location or language restrictions. The identified studies evaluated a range of either, or both, diet and physical activity related policies, or intervention programmes including such policies, using a variety of observational and experimental designs. The policies were clustered into those which sought to affect diet, those which sought to affect physical activity and those which sought to affect both diet and physical activity to undertake random effects meta-analysis. Within the diet cluster, studies of the United States of America National School Lunch and School Breakfast Programs were analysed separately; however there was significant heterogeneity in the pooled results. The pooled effects of the physical activity, and other diet related policies on BMI-SDS were non-significant. The multifaceted interventions tended to include policy elements related to both diet and physical activity (combined cluster), and although these interventions were too varied to pool their results, significant reductions in weight-related outcomes were demonstrated. The evidence from this review suggests that, when implemented alone, school diet and physical activity related policies appear insufficient to prevent or treat overweight or obesity in children, however, they do appear to have an effect when developed and implemented as part of a more extensive intervention programme. Additional evidence is required before recommendations regarding the focus of policies can be made and therefore, increased effort should be made to evaluate the effect of policies and policy containing intervention programmes upon weight status.