Search

Introduction: Advances in development of cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapies mean that now people who are heterozygous (instead of having to be homozygous) for the common F508del variant can benefit from these therapies. Recent economic estimates suggest only approximately 15% of the global population have CFTRm access, yet it is unknown how prevalence of F508del and economic factors may affect this availability., Methods: Data related to prevalence of cystic fibrosis (CF), CFTRm usage, and prevalence of F508del in 10 countries were extracted from publicly accessible registry reports from 2021. National gross domestic product (GDP) was obtained via open access World Bank data. Descriptive statistics and correlation coefficients assessed relationships., Results: Notable discrepancies were noted in the equity of availability of data between national registries-only four countries reported number of patients eligible for CFTRm. Registry data represented 70,694 patients, with 42,858 found to be using CFTRm (60.6%). Prevalence of CFTRm usage ranged from 1.8% to 76.7% and prevalence of F508del ranged from 35.2% to 94.4%. The correlation between prevalence of CFTRm usage and F508del is positive (r = 0.56, p = 0.10), and the correlation between CFTRm usage and GDP (per capita) was also positive, and significant (r = 0.72, p = 0.02)., Conclusion: Both F508del prevalence and GDP are associated with variable CFTRm usage rates, although a predominant reason is unclear as a result of poor consistency in registry reporting. Urgent action is needed to create uniform reporting of registry data and increase availability of novel CFTRm therapies to the global CF population., (© 2024. The Author(s).)

This study investigated the middle cerebral artery blood velocity (MCAv) response to constant work-rate moderate-intensity cycling exercise in 21 children (9.3±0.8 years), 17 adolescents (12.3±0.4 years) and 20 young adults (23.6±2.4 years). Participants completed an incremental ramp test to exhaustion on a cycle ergometer, to determine maximal oxygen uptake and gas exchange threshold (GET), before completing three 6-minute transitions at a moderate-intensity (90% GET), on separate visits. On each visit, bilateral MCAv was measured by transcranial Doppler ultrasonography and breath-by-breath end-tidal carbon dioxide (P ET CO 2 ) via a metabolic cart. Data were ensemble-averaged for each participant and analysed using a mono-exponential model. Absolute MCAv was significantly higher throughout exercise in children and adolescents, compared to adults (P<0.001). Children had a significantly lower relative increase in MCAv from baseline (~12%) compared to adolescents (~20%) and adults (~18%, P<0.040). All adolescents and adults had a mono-exponential rise in MCAv and P ET CO 2 , but this was observed in only eight children. Children and adolescents had a significantly faster MCAv time constant (τ , 12±6 and 14±8 s, respectively) compared to adults (27±9 s, P<0.001). MCAv τ was positively associated with faster P ET CO 2 τ in adolescents (r=0.70, P=0.002) but not children (r=-0.20, P=0.640).Time- and amplitude-based response parameters of MCAv kinetics were significantly associated with P ET CO 2 kinetics in adults (r=0.50 to 0.74, P≤0.025), but not in children (r=-0.19 to -0.48, P>0.227). These findings suggest that the transition from childhood to adulthood impacts the MCAv response to exercise, and the relationships between P ET CO 2 and MCAv kinetics during exercise.

Purpose: To examine the effect of normobaric hypoxia on pulmonary oxygen uptake (V˙O2) and muscle oxygenation kinetics during incremental and moderate-intensity exercise in children., Methods: Eight prepubertal boys (9-11 y) performed incremental cycle tests to exhaustion in both normoxia and hypoxia (fraction of inspired O2 of 15%) followed by repeat 6-minute transitions of moderate-intensity exercise in each condition over subsequent visits., Results: Maximal oxygen uptake (V˙O2max) was reduced in hypoxia compared with normoxia (1.69 [0.20] vs 1.87 [0.26] L·min-1, P = .028), although the gas exchange threshold was not altered in absolute terms (P = .33) or relative to V˙O2max (P = .78). During moderate-intensity exercise, the phase II V˙O2 time constant (τ) was increased in hypoxia (18 [9] vs 24 [8] s, P = .025), with deoxyhemoglobin τ unchanged (17 [8] vs 16 [6], P ≥ .28)., Conclusions: In prepubertal boys, hypoxia reduced V˙O2max and slowed V˙O2 phase II kinetics during moderate-intensity exercise, despite unchanged deoxyhemoglobin kinetics. These data suggest an oxygen delivery dependence of V˙O2max and moderate-intensity V˙O2 kinetics under conditions of reduced oxygen availability in prepubertal boys.

The process of getting one's work published is a major milestone for many in their early academic and clinical careers. However, this process can be confusing and overwhelming for many who have yet to publish themselves. There are differing motivators for publishing work in our early career stages, alongside considerations, such as what we publish, where we decide to submit work, and how we logistically undertake the submission process. This commentary provides a holistic overview for the early career medical educator, empowering them to take the bold steps toward "getting published.", Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Habitual physical activity (PA) and exercise form a cornerstone of the management of cystic fibrosis (CF), a genetically inherited pulmonary and digestive condition - whereby telehealth platforms have been proposed as a mechanism to engage remotely people with CF in PA and exercise., Methods: To test this, in early 2020, the 'ActivOnline: Physical Activity in Cystic Fibrosis Trial' (ActiOn PACT) randomised control trial was established to examine whether an online intervention was effective at increasing PA in adolescents and adults with CF., Results: The emergence of the COVID-19 pandemic in 2020 forced this trial to be paused and modified, with the adoption of online recruitment and remote assessment of outcome measures. Despite such adaptations in accord with frameworks developed by the National Institute for Health Research, this trial failed to recruit and was subsequently terminated., Conclusions: This article details the authors reflections upon the proposed reasons for lack of recruitment, including improved technology and medications for people with CF, and contextualises this finding in relation to the wider issue of non-reporting of trial results in clinical research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “OWT reports speaker fees for Beam – an online exercise platform – undertaken wholly independently of the current trial.”, (© 2024 The Authors.)

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV 1 ) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV 1 , 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV 1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o 2peak ) and peak work rate (W peak ) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P  = 0.008) and 0.60 (0.48-0.82; P  < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified W peak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a W peak  ⩽ 49.2% predicted versus 10.9% for those with a W peak  > 49.2% predicted ( P  < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and W peak appears to be a promising marker for LTX referral and candidate selection.

Background: Academic publishing is a cornerstone of scholarly communications, yet is unfortunately open to abuse, having given rise to 'predatory publishers'- groups that employ aggressive marketing tactics, are deficient in methods and ethics, and bypass peer review. Preventing these predatory publishers from infiltrating scholarly activity is of high importance, and students must be trained in this area to increase awareness and reduce use. The scope of this issue in the context of medical students remains unknown, and therefore this sought to examine the breadth of the current literature base., Methods: A rapid scoping review was undertaken, adhering to adapted PRISMA guidelines. Six databases (ASSIA, EBSCO, Ovid, PubMed, Scopus, Web of Science) were systematically searched for content related to predatory publishing and medical students. Results were single-screened, facilitated by online reviewing software. Resultant data were narratively described, with common themes identified., Results: After searching and screening, five studies were included, representing a total of 1338 students. Two predominant themes- understanding, and utilisation- of predatory publishers was identified. These themes revealed that medical students were broadly unaware of the issue of predatory publishing, and that a small number have already, or would consider, using their services., Conclusion: There remains a lack of understanding of the threat that predatory publishers pose amongst medical students. Future research and education in this domain will be required to focus on informing medical students on the issue, and the implication of engaging with predatory publishers., (© 2024. The Author(s).)

Objective. To quantify the agreement between left and right middle cerebral artery blood velocity (MCAv) responses to incremental and constant work-rate exercise in adults. Approach Seventeen healthy adults (23.8 ± 2.4 years, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer, three 6-minute transitions at a moderate-intensity, and three at a heavy-intensity, all on separate days. Bilateral MCAv was measured throughout using transcranial Doppler ultrasonography, with left and right MCAv data analysed separately. Data were analysed at baseline, gas exchange threshold, respiratory compensation point and exhaustion during ramp incremental exercise. MCAv responses to constant work-rate exercise were analysed using a mono-exponential model, to determine time- and amplitude-based kinetic response parameters. Main Results Left and right MCAv responses to incremental and constant work-rate exercise were significantly, strongly and positively correlated ( r ≥ 0.61, P < 0.01). Coefficient of variation (left versus right) ranged from 7.3%-20.7%, 6.4%-26.2% and 5.9%-22.5% for ramp, moderate and heavy-intensity exercise, respectively. The relative change in MCAv from baseline was higher in the right compared to left MCAv during ramp, moderate and heavy-intensity exercise (all P < 0.05), but the effect sizes were small ( d ≤ 0.4). Small mean left-right differences were present during ramp incremental exercise at all time-points (<6 cm s -1 ; <4%), and for all kinetic parameters during moderate and heavy-intensity exercise (<3 cm s -1 , <3%, <4 s). Significance These findings demonstrate similarities between left and right MCAv responses to incremental and constant-work rate exercise in adults on a group-level, but also highlight individual variation in the agreement between left and right MCAv exercise responses., (Creative Commons Attribution license.)

Background: Increased maximal oxygen uptake (V̇O 2max ) 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 V̇O 2max , although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O 2max 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 V̇O 2max 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 V̇O 2max , once mCSA and TMV were controlled for., Results: V̇O 2max 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 V̇O 2max 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tomlinson, Barker, Fulford, Wilson, Shelley, Oades and Williams.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To conduct a systematic review to evaluate the effects of physiotherapy exercises delivered via telemedicine on lung function and quality-of-life in people with Cystic Fibrosis (CF). The databases AMED, CINAHL and MEDLINE were searched from December 2001 until December 2021. Reference lists of included studies were hand-searched. The PRISMA 2020 statement was used to report the review. Studies of any design reported in the English language, included participants with CF, and within outpatient settings were included. Meta-analysis was not deemed appropriate due to the diversity of interventions and heterogeneity of the included studies. Following screening, eight studies with 180 total participants met the inclusion criteria. Sample sizes ranged from 9 to 41 participants. Research designs included five single cohort intervention studies, two randomised control trials and one feasibility study. Telemedicine-based interventions included Tai-Chi, aerobic, and resistance exercise delivered over a study period of six to twelve weeks. All included studies which measured percentage predicted forced expiratory volume in one second found no significant difference. Five studies measuring the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain found improvements, however, did not meet statistical significance. For the CFQ-R physical domain, measured by five studies, two studies found an improvement, although not statistically significant. No adverse events were reported across all studies. The included studies indicate that telemedicine-based exercise over 6-12 weeks does not significantly change lung function or quality-of-life in people with CF. Whilst the role of telemedicine in the care of pwCF is acceptable and promising; further research with standardised outcome measures, larger sample sizes and longer follow-up are required before clinical practice recommendations can be developed., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Owen W Tomlinson and Jos M Latour report presentation fees obtained from Beam and GE Healthcare respectively., (Copyright: © 2023 Ben Bowhay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cardiopulmonary exercise testing (CPET), and its primary outcome of peak oxygen uptake (VO 2peak ), are acknowledged as biomarkers in the diagnostic and prognostic management of interstitial lung disease (ILD). However, the validity and repeatability of CPET in those with ILD has yet to be fully characterised, and this study fills this evidence gap., Methods: Twenty-six people with ILD were recruited, and 21 successfully completed three CPETs. Of these, 17 completed two valid CPETs within a 3-month window, and 11 completed two valid CPETs within a 6-month window. Technical standards from the European Respiratory Society established validity, and repeatability was determined using mean change, intraclass correlation coefficient and typical error., Results: Every participant (100%) who successfully exercised to volitional exhaustion produced a maximal, and therefore valid, CPET. Approximately 20% of participants presented with a plateau in VO 2 , the primary criteria for establishing a maximal effort. The majority of participants otherwise presented with secondary criteria of respiratory exchange ratios in excess of 1.05, and maximal heart rates in excess of their predicted values. Repeatability analyses identified that the typical error (expressed as percent of coefficient of variation) was 20% over 3-months in those reaching volitional exhaustion., Conclusion: This work has, for the first time, fully characterised how patients with ILD respond to CPET in terms of primary and secondary verification criteria, and generated novel repeatability data that will prove useful in the assessment of disease progression, and future evaluation of therapeutic regimens where VO 2peak is used as an outcome measure., (© 2022. The Author(s).)

Objective: The importance of aerobic fitness (VO 2peak ) in cystic fibrosis (CF) is well established, and regular exercise testing is recommended. To standardise VO 2peak , a 'percentage of predicted' (% pred ) derived from normative reference values (NRV), as promoted by the 2015 European Cystic Fibrosis Society Exercise Working Group (ECFS EWG), can be reported. However, the NRVs used in CF and their relative frequency is unknown., Method: A scoping review was performed via systematic database searches (PubMed, Embase, Web of Science, SciELO, EBSCO) and forward citation searches for studies that include people with CF and report VO 2peak as % pred . Studies were screened using Covidence, and data related to patient demographics, testing modality and reference equations were extracted. Additional analyses were performed on studies published in 2016-2021, following the ECFS EWG statement in 2015., Results: A total of 170 studies were identified, dating from 1984 to 2022, representing 6831 patients with CF, citing 34 NRV. Most studies (154/170) used cycle ergometry, 15/170 used treadmills, and the remainder used alternative, combination or undeclared modalities. In total, 61/170 failed to declare the NRV used. There were 61 studies published since the ECFS EWG statement, whereby 18/61 used the suggested NRV., Conclusion: There is a wide discrepancy in NRV used in the CF literature base to describe VO 2peak as % pred , with few studies using NRV from the ECFS EWG statement. This high variance compromises the interpretation and comparison of studies while leaving them susceptible to misinterpretation and limiting replication. Standardisation and alignment of reporting of VO 2peak values are urgently needed., Competing Interests: Competing interests: OT and CAWa are members of the European Cystic Fibrosis Exercise Working Group. This work is not written on behalf of, nor endorsed by, this group., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to compare the kinetic response of middle cerebral artery blood velocity (MCAv) to moderate- and heavy-intensity cycling in adults, and explore the relationship between maximal oxygen uptake (V̇o 2max ) and MCAv kinetics. Seventeen healthy adults (23.8 ± 2.4 yr, 9 females) completed a ramp incremental test to exhaustion on a cycle ergometer to determine V̇o 2max and the gas exchange threshold (GET). Across six separate visits, participants completed three 6-min transitions at a moderate intensity (90% GET) and three at a heavy intensity (40% of the difference between GET and V̇o 2max ). Bilateral MCAv was measured using transcranial Doppler (TCD) ultrasonography and analyzed using a monoexponential model with a time delay. The time constant (τ) of the MCAv response was not different between moderate- and heavy-intensity cycling (25 ± 10 vs. 26 ± 8 s, P = 0.82), as was the time delay (29 ± 11 vs. 29 ± 10 s, P = 0.95). The amplitude of the exponential increase in MCAv from baseline was greater during heavy-intensity cycling (23.9 ± 10.0 cm·s -1 , 34.1 ± 14.4%) compared with moderate-intensity cycling (12.7 ± 4.4 cm·s -1 , 18.7 ± 7.5%; P < 0.01). Following the exponential increase, a greater fall in MCAv was observed during heavy-intensity exercise compared with moderate-intensity exercise (9.5 ± 6.9 vs. 2.8 ± 3.8 cm·s -1 , P < 0.01). MCAv after 6 min of exercise remained elevated during heavy-intensity exercise compared with moderate-intensity exercise (85.2 ± 9.6 vs. 79.3 ± 7.7 cm·s -1 , P ≤ 0.01). V̇o 2max was not correlated with MCAv τ or amplitude ( r = 0.11-0.26, P > 0.05). These data suggest that the intensity of constant-work rate exercise influences the amplitude, but not time-based, response parameters of MCAv in healthy adults, and found no relationship between cardiorespiratory fitness and MCAv kinetics. NEW & NOTEWORTHY This is the first study to model the MCAv kinetic response to moderate- and heavy-intensity cycling in healthy adults. This study found that the amplitude of the exponential rise in MCAv at exercise onset was greater during heavy-intensity exercise (∼34%) compared with moderate-intensity exercise (∼19%), but the time-based characteristics of the responses were similar between intensities. Higher cardiorespiratory fitness was not associated with a greater or faster MCAv response to moderate- or heavy-intensity exercise.

Objectives: The COVID-19 pandemic has resulted in unprecedent changes to clinical practice, and as the impact upon delivery of exercise services for people with cystic fibrosis (CF) in the United Kingdom was unknown, this was characterised via a national survey., Methods: An electronic survey was distributed to healthcare professionals involved in the exercise management of CF via established professional networks., Results: In total, 31 CF centres participated. Findings included significant reductions in exercise testing and widespread adaptation to deliver exercise training using telehealth methods. Promisingly, 71% stated that they would continue using virtual methods of engaging patients in future practice., Conclusion: These findings highlight adaptation to the COVID-19 pandemic and the need to develop sustainable and standardised telehealth services to manage patients moving forwards., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Cross-sectional studies have reported lower pulmonary and aerobic function during exercise in people with cystic fibrosis-related diabetes (CFRD) compared to non-CFRD counterparts. However, this association has yet to be longitudinally investigated. Therefore, this study examines these differences over time between people with cystic fibrosis (CF) of differing glycaemic status. Annual review data, including cardiopulmonary exercise tests and pulmonary function tests, were retrospectively analysed at baseline (T0, n = 82) and at a one-year follow-up (T1, n = 54). Data was analysed in three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and CFRD. Further analyses were undertaken, with a dichotomous split of NGT and a combined IGT/CFRD group. At baseline, a significant reduction in the majority of variables, including forced expiratory volume in one second (FEV 1 ) and maximal oxygen uptake (VO 2max ), was observed in the CFRD ( n = 19) group compared to NGT ( n = 58). At follow-up, no significant differences were observed, and no interaction effect between CFRD status and time was identified. FEV 1 and VO 2max presented with varying directions and magnitudes of change within patients. In summary, patients with CFRD have a reduced aerobic and pulmonary function compared to non-CFRD counterparts, although such changes disappeared at follow up. Varying responses for FEV 1 and VO 2max highlight the need to consider both variables as independent markers of function in CF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tomlinson, Stoate, Dobson and Williams.)

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 30 th June and 1 st 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.

Regulation of cerebral blood flow during exercise in youth is poorly understood. This study investigated the cerebrovascular and ventilatory responses to a ramp incremental cycle test to exhaustion in 14 children (means ± SD age: 9.4 ± 0.9 yr), 14 adolescents (12.4 ± 0.4 yr), and 19 adults (23.4 ± 2.5 yr). Middle cerebral artery blood velocity (MCAv), partial pressure of end-tidal CO 2 ([Formula: see text]), and ventilatory parameters were analyzed at baseline, gas exchange threshold (GET), respiratory compensation point (RCP), and exhaustion. The increase in minute ventilation relative to CO 2 production during exercise was also calculated (V̇e/V̇co 2 slope). Relative change from baseline (Δ%) in MCAv was lower in children, compared with adolescents and adults at GET [15 ± 10% vs. 26 ± 14%, and 24 ± 10%, respectively, P ≤ 0.03, effect size ( d ) = 0.9] and RCP (13 ± 11% vs. 24 ± 16% and 27 ± 15%, respectively, P ≤ 0.05, d  ≥   0.8). Δ%MCAv was similar in adults and adolescents at all intensities and similar in all groups at exhaustion. The magnitude of the V̇ E /V̇co 2 slope was negatively associated with Δ%MCAv at GET and RCP across all participants ( P ≤ 0.01, r = -0.37 to -0.48). Δ%[Formula: see text] was smaller in children and adolescents compared with adults at GET and RCP ( P ≤ 0.05, d  ≥   0.6). In children, Δ%[Formula: see text] and Δ%MCAv were not associated from baseline-GET ( r¯  = 0.14) and were moderately associated from RCP-exhaustion ( r¯  = 0.49). These relationships strengthened with increasing age and were stronger in adolescents (baseline-GET: r¯  = 0.47, RCP-exhaustion: r¯  = 0.62) and adults (baseline-GET: r¯  = 0.66, RCP-exhaustion: r¯  = 0.78). These findings provide the first evidence on the development of the regulatory role of [Formula: see text] on MCAv during exercise in children, adolescents, and adults. NEW & NOTEWORTHY This is the first study to observe similar increases in cerebral blood flow during incremental exercise in adolescents and adults. Increases in cerebral blood flow during exercise were smaller in children compared with adolescents and adults and were associated with a greater V̇ E /V̇co 2 slope. This study also provides the first evidence on the progressive development of the regulatory role of end-tidal CO 2 on cerebral blood flow during exercise during the transition from childhood to adulthood.

Background: Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF., Methods: A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity., Discussion: This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF., Systematic Review Registration: PROSPERO CRD42020184411.

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.

Background: The benefits of physical activity (PA) for people with cystic fibrosis (pwCF) are widely accepted, yet how PA is promoted and utilised by pwCF is unclear., Method: An online questionnaire to explore attitudes, practices and promotion of PA in cystic fibrosis was completed by healthcare providers (HCP), pwCF and parents/caregivers., Results: 351 respondents (105 HCP, 120 pwCF, and 126 parents/caregivers) from 12 countries completed the survey. Importance of PA was rated highly by the majority of respondents. Physical ( e.g. health), psychological ( e.g. enjoyment) and social ( e.g. social interaction) factors were motives for PA for 82%, 49% and 37% of pwCF, respectively, irrespective of country. Common barriers to PA included time (49% and 36%) and tiredness (61% and 7%) for pwCF and parents/carers, respectively. pwCF also reported psychosocial barriers ( e.g. stigma, demoralisation), while parents/caregivers reported structural barriers ( e.g. cost). Clinical teams varied substantially in terms of the emphasis placed on PA, facilities available, staff and training, and advice given to pwCF., Conclusion: Despite the majority of participants rating the importance of PA highly, substantial variability was evident regarding the facilities and clinical support available to them, as well as why and how people were active. There remains a need to identify what constitutes "best practice" for PA promotion within clinics., Competing Interests: Conflict of interest: S. Denford reports grants from Cystic Fibrosis Trust during the conduct of the study. Conflict of interest: N.S. Cox has nothing to disclose. Conflict of interest: K.A. Mackintosh has nothing to disclose. Conflict of interest: M.A. McNarry has nothing to disclose. Conflict of interest: P. O'Halloran has nothing to disclose. Conflict of interest: A.E. Holland has nothing to disclose. Conflict of interest: O.W. Tomlinson has nothing to disclose. Conflict of interest: A.R. Barker reports grants from Cystic Fibrosis Trust Strategic Research Centre award during the conduct of the study. Conflict of interest: C.A. Williams reports grants from Cystic Fibrosis Trust during the conduct of the study., (Copyright ©ERS 2020.)

Introduction: Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown., Methods: Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed., Results: Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period., Discussion: The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes.

Background: Regular participation in physical activity by people with cystic fibrosis (CF) promotes positive clinical and health outcomes including reduced rate of decline in lung function, fewer hospitalizations and greater wellbeing. However adherence to exercise and activity programs is low, in part due to the substantial daily therapy burden for young people with CF. Strict infection control requirements limit the role of group exercise programs that are commonly used in other clinical groups. Investigation of methods to promote physical activity in this group has been limited. The Active Online Physical Activity in Cystic fibrosis Trial (ActionPACT) is an assessor-blinded, multi-centre, randomized controlled trial designed to compare the efficacy of a novel web-based program (ActivOnline) compared to usual care in promoting physical activity participation in adolescents and young adults with CF., Methods: Adolescents and young adults with CF will be recruited on discharge from hospital for a respiratory exacerbation. Participants randomized to the intervention group will have access to a web-based physical activity platform for the 12-week intervention period. ActivOnline allows users to track their physical activity, set goals, and self-monitor progress. All participants in both groups will be provided with standardised information regarding general physical activity recommendations for adolescents and young adults. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and at 3-months followup. Healthcare utilization will be assessed at 12 months from intervention completion. The primary outcome is change in moderate-to-vigorous physical activity participation measured objectively by accelerometry. Secondary outcomes include aerobic fitness, health-related quality of life, anxiety and depression and sleep quality., Discussion: This trial will establish whether a web-based application can improve physical activity participation more effectively than usual care in the period following hospitalization for a respiratory exacerbation. The web-based application under investigation can be made readily and widely available to all individuals with CF, to support physical activity and exercise participation at a time and location of the user's choosing, regardless of microbiological status., Trial Registration: Clinical trial registered on July 13, 2017 with the Australian and New Zealand Clinical Trials Register at (ACTRN12617001009303).

Purpose : This study had 2 objectives: (1) to examine whether the validity of the supramaximal verification test for maximal oxygen uptake ( V ˙ O 2 max ) differs in children and adolescents when stratified for sex, body mass, and cardiorespiratory fitness and (2) to assess sensitivity and specificity of primary and secondary objective criteria from the incremental test to verify V ˙ O 2 max . Methods : In total, 128 children and adolescents (76 male and 52 females; age: 9.3-17.4 y) performed a ramp-incremental test to exhaustion on a cycle ergometer followed by a supramaximal test to verify V ˙ O 2 max . Results : Supramaximal tests verified V ˙ O 2 max in 88% of participants. Group incremental test peak V ˙ O 2 was greater than the supramaximal test (2.27 [0.65] L·min -1 and 2.17 [0.63] L·min -1 ; P  < .001), although both were correlated ( r  = .94; P  < .001). No differences were found in V ˙ O 2 plateau attainment or supramaximal test verification between sex, body mass, or cardiorespiratory fitness groups (all P s > .18). Supramaximal test time to exhaustion predicted supramaximal test V ˙ O 2 max verification ( P  = .04). Primary and secondary objective criteria had insufficient sensitivity (7.1%-24.1%) and specificity (50%-100%) to verify V ˙ O 2 max . Conclusion : The utility of supramaximal testing to verify V ˙ O 2 max is not affected by sex, body mass, or cardiorespiratory fitness status. Supramaximal testing should replace secondary objective criteria to verify V ˙ O 2 max .

Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at individual patient level. Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients' data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the gas exchange threshold (GET) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict GET at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting an example and future perspectives for improving and extending the proposed framework. The modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient's treatment therapies., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study characterised oxygen uptake efficiency (OUE) in children with mild-to-moderate cystic fibrosis (CF). Specifically, it investigated (1) the utility of OUE parameters as potential submaximal surrogates of peak oxygen uptake ([Formula: see text]), and (2) the relationship between OUE and disease severity., Methods: Cardiopulmonary exercise test (CPET) data were collated from 72 children [36 CF, 36 age- and sex-matched controls (CON)], with OUE assessed as its highest 90-s average (plateau; OUEP), the gas exchange threshold (OUE GET ) and respiratory compensation point (OUE RCP ). Pearson's correlation coefficients, independent t tests and factorial ANOVAs assessed differences between groups and the use of OUE measures as surrogates for [Formula: see text]., Results: A significant (p < 0.05) reduction in allometrically scaled [Formula: see text] and all OUE parameters was found in CF. Significant (p < 0.05) correlations between measurements of OUE and allometrically scaled [Formula: see text], were observed in CF (r = 0.49-0.52) and CON (r = 0.46-0.52). Furthermore, measures of OUE were significantly (p < 0.05) correlated with pulmonary function (FEV 1%predicted ) in CF (r = 0.38-0.46), but not CON (r = -0.20-0.14). OUEP was able to differentiate between different aerobic fitness tertiles in CON but not CF., Conclusions: OUE parameters were reduced in CF, but were not a suitable surrogate for [Formula: see text]. Clinical teams should, where possible, continue to utilise maximal CPET parameters to measure aerobic fitness in children and adolescents with CF. Future research should assess the prognostic utility of OUEP as it does appear sensitive to disease status and severity.

Background: Maximal cardiopulmonary exercise testing is recommended on an annual basis for children with cystic fibrosis (CF), due to clinically useful prognostic information provided by maximal oxygen uptake (V̇O 2max ). However, not all patients are able, or willing, to reach V̇O 2max , and therefore submaximal alternatives are required. This study explored the validity of the oxygen uptake efficiency slope (OUES) as a submaximal measure of V̇O 2max in children and adolescents with CF., Methods: Data were collated from 72 cardiopulmonary exercise tests (36 CF, 36 controls), with OUES determined relative to maximal and submaximal parameters of exercise intensity, time, and individual metabolic thresholds. Pearson's correlation coefficients, independent t-tests, and factorial ANOVAs were used to determine validity., Results: Significant (P < 0.05) correlations with V̇O 2max were observed for most expressions of OUES, but were consistently weaker in CF (r = 0.30-0.47) when compared to CON (r = 0.58-0.89). Mean differences for all OUES parameters between groups were not significant (P > 0.05). When split by V̇O 2max tertiles, minimal significant differences were found between, and within, groups for OUES, indicating poor discrimination of V̇O 2max ., Conclusions: The OUES is not a valid (sub) maximal measure of V̇O 2max in children and adolescents with mild-to-moderate CF. Clinicians should continue to use maximal markers (ie, V̇O 2max ) of exercise capacity., (© 2017 Wiley Periodicals, Inc.)

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.

Cystic fibrosis (CF) is a genetic condition affecting the respiratory and gastrointestinal systems, with patients experiencing problems maintaining weight, especially during rapid growth periods such as puberty. The aim of this case report was to monitor the effect of gastrostomy insertion and implementation of overnight supplemental feeding upon clinical outcomes, including body mass index (BMI), lung function (FEV 1 ), and exercise-related variables (maximal oxygen uptake [VO 2max ] and ventilatory efficiency [V E /VO 2 ]) in an 11-year-old female with CF Combined incremental and supramaximal exercise testing to exhaustion was performed at four time points: 3 months prior to the procedure (T1), 2 days prior to (T2), 4 months (T3), and 1 year following the procedure (T4). Improvements following gastrostomy insertion were observed at the 1 year follow-up with regards to BMI (+20%); whereas absolute VO 2max remained stable and lung function fluctuated throughout the period of observation. Declines in function with regards to body weight relative VO 2max (-16.3%) and oxygen uptake efficiency (+7.5%) were observed during this period. This case report is the first to consider exercise-related clinical outcomes in assessing the effect of implementing gastrostomy feeding in CF The varied direction and magnitude of the associations between variables shows that further investigations are required., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Objectives: High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys., Design: Within-measures design with counterbalanced experimental conditions., Methods: Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale., Results: The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01)., Conclusion: A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise., (Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Cardiopulmonary exercise testing is underutilized within the clinical management of patients with cystic fibrosis. But within the last 5 years, there has been considerable interest in its implementation, which has included deliberations by the European Cystic Fibrosis Society about incorporating this method within the clinical assessment of patients. This review examines the current use of cardiopulmonary exercise testing in assessing the extent and cause(s) of exercise limitation from a pediatric perspective. Examples of the measured parameters and their interpretation are provided. Critical synthesis of recent work in the oxygen uptake (VO2) kinetics response to and following exercise is also discussed, and although identified more as a research tool, its utilization advances researchers understanding of the cardiovascular, respiratory and muscular limitations to exercise tolerance. Finally, exercise and its application in therapeutic interventions are highlighted and a number of recommendations made about the utility of exercise prescription.