The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus.

BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.

Physiological stress reactivity in pediatric cancer survivors treated with chemotherapy.

Children who experience early life stress demonstrate changes to their stress responses, which may modulate long-term health. Childhood cancer presents significant stress during diagnosis, treatment, and survivorship. We hypothesized that children who have completed chemotherapy treatment for ALL will demonstrate altered hormone patterns in response to a stressor compared with healthy controls. Twelve pediatric ALL survivors and 12 healthy controls completed the Trier Social Stress Test. Salivary samples, heart rate, and self-report ratings of stress were collected at baseline, pretest, and posttest. Between group comparison showed baseline (interleukin [IL]-8) was significantly higher in the survivor group versus controls (survivors: 89.9, 40.1-544.9 pg ml-1 ; controls: 30.7, 5.6-241.9 pg ml-1 , p = .001) as was peak (IL-8) (survivors: 147.1, 71.6-1177.6 pg ml-1 ; controls: 75.5, 28.6-698.6 pg ml-1 ). Peak salivary alpha-amylase (sAA) concentration was significantly lower in the survivor group (survivors: 69.3, 19.4-195.5 U ml-1 ; controls: 91.2, 27.7-213.7 U ml-1 ; p = .04). Repeated measures ANOVA revealed significant main effects for time on cortisol (F(2.35, 50.81)  = 5.9, p < .01), sAA (F(1.56, 33.17)  = 6.6, p < .01), stress ratings (F(3.42, 88.14)  = 53.4, p < .001), and heart rate (F(8, 83)  = 16.8, p < .05). Significant main effects for group were observed for IL-8 (F(1, 23)  = 8.2, p < .01) and tumor necrosis factor-α (F(1, 23)  = 6.8, p < .05). Significant interaction effects for group × time were found for sAA (F(5, 106)  = 2.8, p < .05). Our results indicate that childhood ALL survivors have similar responses to stress as healthy controls, but lower sympatho-adrenal-medullary reactivity. Therefore, altered stress regulation may present a pathway modulating long-term health in this population.

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort.

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise.

Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma.

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function ( P =0.14, d =0.72), slower metabolic recovery ( P =0.08, d =0.93), and lower mechanical muscle power ( d =1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO 2peak (41.61±5.97 vs. 47.71±9.99 mL/min/kg, P =0.11, d =0.76), lower minutes of physical activity (58.3±35.3 vs. 114.8±79.3 min, P =0.12, d =0.99) and higher minutes of inactivity (107.3±74.0 vs. 43.5±48.3 min, d =1.04, P <0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.

Exercise intolerance in cystic fibrosis-the role of CFTR modulator therapies.

Exercise intolerance is common in people with CF (pwCF), but not universal among all individuals. While associated with disease prognosis, exercise intolerance is not simply a reflection of the degree of lung disease. In people with severe CF, respiratory limitations may contribute more significantly to impaired exercise capacity than in those with mild-moderate CF. At all levels of disease severity, there are peripheral factors e.g., abnormal macro- and micro-vascular function that impair blood flow and reduce oxygen extraction, and mitochondrial defects that diminish metabolic efficiency. We discuss advances in understanding the central and peripheral mechanisms underlying exercise intolerance in pwCF. Exploring both the central and peripheral factors that contribute to exercise intolerance in CF can help inform the development of new therapeutic targets, as well as help define prognostic criteria.

The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients.

Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease.

Massage Therapy Modulates Inflammatory Mediators Following Sprint Exercise in Healthy Male Athletes.

Massage therapy is a common postexercise muscle recovery modality; however, its mechanisms of efficacy are uncertain. We evaluated the effects of massage on systemic inflammatory responses to exercise and postexercise muscle performance and soreness. In this crossover study, nine healthy male athletes completed a high-intensity intermittent sprint protocol, followed by massage therapy or control condition. Inflammatory markers were assessed pre-exercise; postexercise; and at 1, 2, and 24 h postexercise. Muscle performance was measured by squat and drop jump, and muscle soreness on a Likert scale. Significant time effects were observed for monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), drop jump performance, squat jump performance, and soreness. No significant effects for condition were observed. However, compared with control, inflammatory marker concentrations (IL-8, TNFα, and MCP-1) returned to baseline levels earlier following the massage therapy condition (p < 0.05 for all). IL-6 returned to baseline levels earlier following the control versus massage therapy condition (p < 0.05). No differences were observed for performance or soreness variables. MCP-1 area under the curve (AUC) was negatively associated with squat and drop jump performance, while IL-10 AUC was positively associated with drop jump performance (p < 0.05 for all). In conclusion, massage therapy promotes resolution of systemic inflammatory signaling following exercise but does not appear to improve performance or soreness measurements.

Skeletal Muscle Dysfunction and Exercise Intolerance in Children Treated with Haematopoietic Stem Cell Transplant-A Pilot Feasibility Study.

Haematopoietic stem cell transplant (HSCT) is an intensive therapy for some pediatric hematological illnesses. Survivors are at risk for adverse effects including exercise intolerance. Peripheral tissue dysfunction may contribute to exercise intolerance; therefore, we examined the feasibility of a magnetic resonance spectroscopy (MRS) protocol to evaluate skeletal muscle metabolism in children post-HSCT. We measured demographic characteristics, aerobic exercise capacity (YMCA protocol), and skeletal muscle function in response to exercise (MRS; Siemens 3T MRI) in five children post-allogeneic HSCT and five age/body mass index-matched healthy controls (HCs). The mean age (± standard deviation) of the HSCT group and HC group were 11 ± 1.2 and 12.8 ± 2.4 years, respectively. Children post-HSCT had a lower peak aerobic exercise capacity compared to HCs (27.8 ± 3.4 vs. 40.3 ± 8.1 mL kg-1 min-1, respectively; p = 0.015). Exercise MRS testing protocols were successfully completed by all HSCT and HC participants; however, MRS-derived skeletal muscle metabolism variables were not different between the two groups. In conclusion, the use of exercise protocols in conjunction with MRS to assess peripheral skeletal muscle metabolism was achievable in children post-HSCT. In the future, larger studies should determine if skeletal muscle function is associated with exercise capacity in children post-HSCT.

Physical activity for children with chronic disease; a narrative review and practical applications.

BACKGROUND: Physical activity (PA) is associated with a diverse range of health benefits. International guidelines suggest that children should be participating in a minimum of 60 min of moderate to vigorous intensity PA per day to achieve these benefits. However, current guidelines are intended for healthy children, and thus may not be applicable to children with a chronic disease. Specifically, the dose of PA and disease specific exercise considerations are not included in these guidelines, leaving such children with few, if any, evidence-based informed suggestions pertaining to PA. Thus, the purpose of this narrative review was to consider current literature in the area of exercise as medicine and provide practical applications for exercise in five prevalent pediatric chronic diseases: respiratory, congenital heart, metabolic, systemic inflammatory/autoimmune, and cancer. METHODS: For each disease, we present the pathophysiology of exercise intolerance, summarize the pediatric exercise intervention research, and provide PA suggestions. RESULTS: Overall, exercise intolerance is prevalent in pediatric chronic disease. PA is important and safe for most children with a chronic disease, however exercise prescription should involve the entire health care team to create an individualized program. CONCLUSIONS: Future research, including a systematic review to create evidence-based guidelines, is needed to better understand the safety and efficacy of exercise among children with chronic disease.