Adapting, restarting, and terminating a randomised control trial for people with cystic fibrosis: Reflections on the impact of the COVID-19 pandemic upon research in a clinical population.

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.

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

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 (FEV1) ⩽ 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 (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) 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 Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

The use of 2-D speckle tracking echocardiography in differentiating healthy adolescent athletes with right ventricular outflow tract dilation from patients with arrhythmogenic cardiomyopathy.

AIMS: Echocardiographic assessment of adolescent athletes for arrhythmogenic cardiomyopathy (ACM) can be challenging owing to right ventricular (RV) exercise-related remodelling, particularly RV outflow tract (RVOT) dilation. The aim of this study is to evaluate the role of RV 2-D speckle tracking echocardiography (STE) in comparing healthy adolescent athletes with and without RVOT dilation to patients with ACM. METHODS AND RESULTS: A total of 391 adolescent athletes, mean age 14.5 ± 1.7 years, evaluated at three sports academies between 2014 and 2019 were included, and compared to previously reported ACM patients (n = 38 definite and n = 39 borderline). Peak systolic RV free wall (RVFW-Sl), global and segmental strain (Sl), and corresponding strain rates (SRl) were calculated. The participants meeting the major modified Task Force Criteria (mTFC) for RVOT dilation were defined as mTFC+ (n = 58, 14.8%), and the rest as mTFC- (n = 333, 85.2%). Mean RVFW-Sl was -27.6 ± 3.4% overall, -28.2 ± 4.1% in the mTFC+ group and - 27.5 ± 3.3% in the mTFC- group. mTFC+ athletes had normal RV-FW-Sl when compared to definite (-29% vs -19%, p < 0.001) and borderline ACM (-29% vs -21%, p < 0.001) cohorts. In addition, all mean global and regional Sl and SRl values were no worse in the mTFC+ group compared to the mTFC- (p values range < 0.0001 to 0.1, inferiority margin of 2% and 0.1 s-1 respectively). CONCLUSIONS: In athletes with RVOT dilation meeting the major mTFC, STE evaluation of the RV can demostrate normal function and differentiate physiological remodelling from pathological changes found in ACM, improving screening in grey-area cases.

Systematic review and meta-analysis: Associations of vitamin D with pulmonary function in children and young people with cystic fibrosis.

BACKGROUND: Increasing evidence suggests that vitamin D is associated with pulmonary health, which may benefit children and young people diagnosed with Cystic Fibrosis (cypCF). Therefore, the aim of this systematic review was to evaluate primary research to establish associations between 25OHD and pulmonary health in cypCF. METHODS: Electronic databases were searched with keywords related to CF, vitamin D, children/young people and pulmonary function. Included studies were cypCF (aged ≤21 years) treated in a paediatric setting. The primary outcome was lung function [forced expiratory volume in 1 s (FEV1% predicted)] and secondary outcomes were rate of pulmonary exacerbations, 25OHD status and growth. Evidence was appraised for risk of bias using the CASP tool, and quality using the EPHPP tool. A Meta-analysis was performed. RESULTS: Twenty-one studies were included with mixed quality ratings and heterogeneity of reported outcomes. The Meta-analysis including 5 studies showed a significantly higher FEV1% predicted in the 25OHD sufficiency compared to the deficiency group [FEV1% predicted mean difference (95% CI) was 7.71 (1.69-13.74) %; p = 0.01]. The mean ± SD FEV1% predicted for the sufficient (≥75 nmol/L) vs. deficient (<50 nmol/L) group was 94.7 ± 31.9% vs. 86.9 ± 13.2%; I2 = 0%; χ2 = 0.5; df = 4). Five studies (5/21) found significantly higher rate of pulmonary exacerbations in those who were 25OHD deficient when compared to the sufficient group and negative associations between 25OHD and FEV% predicted. The effects of vitamin D supplementation dosages on 25OHD status (10/21) varied across studies and no study (12/21) showed associations between 25OHD concentration and growth. CONCLUSION: This systematic review suggests that 25OHD concentration is positively associated with lung function and a concentration of >75 nmol/L is associated with reduced frequency of pulmonary exacerbations, which may slow lung function decline in cypCF. Future randomised clinical trials and mechanistic studies are warranted.

Expert guidelines on exercise and physical activity for people with cystic fibrosis.

Research has shown that there is a lack of confidence and understanding in how to use exercise for managing cystic fibrosis. This editorial discusses the key points of a consensus statement that highlights what is and is not known about the relationship between cystic fibrosis and exercise.

Normal reference values for aerobic fitness in cystic fibrosis: a scoping review.

Objective: The importance of aerobic fitness (VO2peak) in cystic fibrosis (CF) is well established, and regular exercise testing is recommended. To standardise VO2peak, 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 VO2peak 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 VO2peak 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 VO2peak values are urgently needed.

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.

Sleep, Sedentary Time and Physical Activity Levels in Children with Cystic Fibrosis.

The aim of this study was to compare the use of generic and cystic fibrosis (CF)-specific cut-points to assess movement behaviours in children and adolescents with CF. Physical activity (PA) was assessed for seven consecutive days using a non-dominant wrist-worn ActiGraph GT9X in 71 children and adolescents (36 girls; 13.5 ± 2.9 years) with mild CF. CF-specific and generic Euclidean norm minus one (ENMO) cut-points were used to determine sedentary time (SED), sleep, light physical activity (LPA), moderate physical activity and vigorous physical activity. The effect of using a CF-specific or generic cut-point on the relationship between PA intensities and lung function was determined. Movement behaviours differed significantly according to the cut-point used, with the CF-specific cut-points resulting in less time asleep (−31.4 min; p < 0.01) and in LPA (−195.1 min; p < 0.001), and more SED and moderate-to-vigorous PA (159.3 and 67.1 min, respectively; both p < 0.0001) than the generic thresholds. Lung function was significantly associated with LPA according to the CF-specific cut-points (r = 0.52; p = 0.04). Thresholds developed for healthy populations misclassified PA levels, sleep and SED in children and adolescents with CF. This discrepancy affected the relationship between lung function and PA, which was only apparent when using the CF-specific cut-points. Promoting LPA seems a promising strategy to enhance lung function in children and adolescents with CF.

A Compositional Analysis of Physical Activity, Sedentary Time, and Sleep and Associated Health Outcomes in Children and Adults with Cystic Fibrosis.

This study sought to investigate the association of light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time (SED), and sleep with lung function in children and adults with CF. In total, 86 children (41 females; 13.6 ± 2.8 years; FEV1%predicted: 86 ± 1%) and 43 adults (21 females; 24.6 ± 4.7 years; FEV1%predicted: 63 ± 21%) with CF participated in this study. Wrist-worn accelerometery was used to assess PA, SED and sleep. Compositional linear regression models were conducted following normalisation via isometric log-ratio transformations. Sequential binary partitioning was applied to investigate the impact of reallocating 10 to 30 min between each behaviour on FEV1%predicted. A decline in FEV1%predicted was predicted with the reallocation of 30 min from MVPA to SED or LPA or sleep to any other behaviour in children (-3.04--0.005%) and adults (-3.58--0.005%). Conversely, improvements in FEV1%predicted were predicted when 30 min was reallocated to MVPA from LPA or SED in children (0.12-1.59%) and adults (0.77-2.10%), or when 30 min was reallocated to sleep from any other behaviour in both children (0.23-2.56%) and adults (1.08-3.58%). This study supports the importance of MVPA and sleep for maintaining and promoting lung function in people with CF.

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.

The Effect of Dysglycaemia on Changes in Pulmonary and Aerobic Function in Cystic Fibrosis.

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 (FEV1) and maximal oxygen uptake (VO2max), 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. FEV1 and VO2max 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 FEV1 and VO2max highlight the need to consider both variables as independent markers of function in CF.

The impact of COVID-19 upon the delivery of exercise services within cystic fibrosis clinics in the United Kingdom.

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.

Investigating the Accuracy of Quantitative Echocardiographic-Modified Task Force Criteria for Arrhythmogenic Ventricular Cardiomyopathy in Adolescent Male Elite Athletes.

Athlete preparticipation screening focuses on preventing sudden cardiac death (SCD) by detecting diseases such as arrhythmogenic ventricular cardiomyopathy (AVC), which affects primarily the right ventricular myocardium. Diagnosis may be obscured by physiological remodeling of the athlete heart. Healthy athletes may meet the 2010 Task Force Criteria right ventricular outflow tract (RVOT) dimension cut-offs, questioning the suitability of the modified Task Force Criteria (mTFC) in adolescent athletes. In this study, 67 male adolescent footballers undergoing preparticipation screening were reviewed. All athletes underwent a screening for resting ECG and echocardiogram according to the English FA protocol, as well as cardiopulmonary exercise testing, stress ECG, and exercise echocardiography. Athletes' right ventricular outflow tract (RVOT) that met the major AVC diagnostic criteria for dilatation were identified. Of 67 evaluated athletes, 7 had RVOT dilatation that met the major criteria, all in the long axis parasternal view measurement. All had normal right ventricular systolic function, including normal free-wall longitudinal strain (ranging from - 21.5 to - 32.7%). Left ventricular ejection fraction ranged from 52 to 67%, without evidence of structural changes. Resting ECGs and cardiopulmonary exercise tests were normal in all individuals. In a series of healthy athletes meeting the major AVC diagnostic criteria for RVOT dilatation, none had any other pathological changes on a detailed screening including ECG, exercise testing, and echocardiography. This report highlights that current AVC echocardiographic diagnosis criteria have limitations 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 impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review.

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.

Physical activity for cystic fibrosis: perceptions of people with cystic fibrosis, parents and healthcare professionals.

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.

A web-based intervention to promote physical activity in adolescents and young adults with cystic fibrosis: protocol for a randomized controlled trial.

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).

Cardiopulmonary responses to maximal aerobic exercise in patients with cystic fibrosis.

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.

Analysis of oxygen uptake efficiency parameters in young people with cystic fibrosis.

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 (OUEGET) and respiratory compensation point (OUERCP). 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 (FEV1%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.