The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease.

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.

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.

Standards for the care of people with cystic fibrosis; establishing and maintaining health.

This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.

The effect of repeated hot water immersion on insulin sensitivity, heat shock protein 70, and inflammation in individuals with type 2 diabetes mellitus.

Repeated hot water immersion (HWI) can improve glycemic control in healthy individuals but data are limited for individuals with type 2 diabetes mellitus (T2DM). The present study investigated whether repeated HWI improves insulin sensitivity and inflammatory status and reduces plasma ([extracellular heat shock protein 70]) [eHSP70] and resting metabolic rate (RMR). Fourteen individuals with T2DM participated in this pre- versus postintervention study, with outcome measures assessed in fasted (≥12 h) and postprandial (2-h post-75 g glucose ingestion) states. HWI consisted of 1 h in 40°C water (target rectal temperature 38.5°C-39°C) repeated 8-10 times within a 14-day period. Outcome measures included insulin sensitivity, plasma [glucose], [insulin], [eHSP70], inflammatory markers, RMR, and substrate utilization. The HWI intervention increased fasted insulin sensitivity (QUICKI; P = 0.03) and lowered fasted plasma [insulin] (P = 0.04), but fasting plasma [glucose] (P = 0.83), [eHSP70] (P = 0.08), [IL-6] (P = 0.55), [IL-10] (P = 0.59), postprandial insulin sensitivity (P = 0.19), plasma [glucose] (P = 0.40), and [insulin] (P = 0.47) were not different. RMR was reduced by 6.63% (P < 0.05), although carbohydrate (P = 0.43) and fat oxidation (P = 0.99) rates were unchanged. This study shows that 8-10 HWIs within a 14-day period improved fasting insulin sensitivity and plasma [insulin] in individuals with T2DM, but not when glucose tolerance is challenged. HWI also improves metabolic efficiency (i.e., reduced RMR). Together these results could be clinically important and have implications for metabolic health outcomes and well-being in individuals with T2DM.NEW & NOTEWORTHY This is the first study to investigate repeated HWI to raise deep body temperature on insulin sensitivity, inflammation, eHSP70, and substrate utilization in individuals with T2DM. The principal novel findings were improvements in fasting insulin sensitivity and fasting plasma [insulin] but no change in fasting plasma [glucose], postprandial insulin sensitivity, plasma [insulin], or [glucose]. There was also no change in eHSP70, inflammatory status, or substrate utilization but there were reductions in RMR and oxygen consumption.

Guidance and standard operating procedures for functional exercise testing in cystic fibrosis.

Regular exercise testing is recommended for all people with cystic fibrosis (PwCF). A range of validated tests, which integrate both strength and aerobic function, are available and increasingly being used. Together, these tests offer the ability for comprehensive exercise evaluation. Extensive research and expert consensus over recent years has enabled the adaptation and standardisation of a range of exercise tests to aid the understanding of the pathophysiology related to exercise limitation in PwCF and has led to the development of novel exercise tests which may be applied to PwCF. This article provides expert, opinion-based clinical practice guidance, along with test instructions, for a selection of commonly used valid tests which have documented clinimetric properties for PwCF. Importantly, this document also highlights previously used tests that are no longer suggested for PwCF and areas where research is mandated. This collaboration, on behalf of the European Cystic Fibrosis Society Exercise Working Group, represents expert consensus by a multidisciplinary panel of physiotherapists, exercise scientists and clinicians and aims to improve global standardisation of functional exercise testing of PwCF. In short, the standardised use of a small selection of tests performed to a high standard is advocated.

Heterogeneous Treatment Effects after Inspiratory Muscle Training during Recovery from Postacute COVID-19 Syndrome.

PURPOSE: The objective of this study is to investigate whether heterogeneous treatment effects occur for changes in inspiratory muscle strength, perceived dyspnea, and health-related quality of life after 8 wk of unsupervised home-based inspiratory muscle training (IMT) in adults with postacute coronavirus disease 2019 (COVID-19) syndrome. METHODS: In total, 147 adults with self-reported prior COVID-19 either completed an 8-wk home-based IMT intervention ( n = 111, 92 females, 48 ± 11 yr, 9.3 ± 3.6 months postacute COVID-19 infection) or acted as "usual care" wait list controls ( n = 36, 34 females, 49 ± 12 yr, 9.4 ± 3.2 months postacute COVID-19 infection). RESULTS: Applying a Bayesian framework, we found clear evidence of heterogeneity of treatment response for inspiratory muscle strength: the estimated difference between standard deviations (SD) of the IMT and control groups was 22.8 cm H 2 O (75% credible interval (CrI), 4.7-37.7) for changes in maximal inspiratory pressure (MIP) and 86.8 pressure time units (75% CrI, 55.7-116.7) for sustained MIP (SMIP). Conversely, there were minimal differences in the SD between the IMT and the control group for changes in perceived dyspnea and health-related quality of life, providing no evidence of heterogeneous treatment effects. Higher cumulative power during the IMT intervention was related to changes in MIP ( ß = 10.9 cm H 2 O (95% CrI, 5.3-16.8) per 1 SD) and SMIP ( ß = 63.7 (32.2-95.3) pressure time units per 1 SD), clearly indicating an IMT dose response for changes in inspiratory muscle strength. Older age (>50 yr), a longer time postacute COVID-19 (>3 months), and greater severity of dyspnea at baseline were also associated with smaller improvements in inspiratory muscle strength. CONCLUSIONS: Heterogeneous individual responses occurred after an 8-wk home-based IMT program in people with postacute COVID-19 syndrome. Consistent with standard exercise theory, larger improvements in inspiratory muscle strength are strongly related to a greater cumulative dose of IMT.

Battling the unknown: Using composite vignettes to portray lived experiences of COVID-19 and long-COVID.

Understanding the day-to-day lived experiences of individuals who have had or are still recovering from Coronavirus Disease-19 (COVID-19), whilst a complex challenge, presents the opportunity to listen and learn. Composite vignettes provide a novel approach to explore and present descriptive portrayals of the most commonly derived experiences and recovery journeys. The thematic analysis of 47 shared accounts (semi-structured interviews with adults aged ≥18 years; 40 females; 6-11 months post-COVID-19 infection) produced a series of four intricate character stories written through the lens of a single individual. Each vignette gives a voice to and captures a different experience trajectory. From the point of initial symptom development onwards, the vignettes depict how COVID-19 has affected everyday lives, focusing on the secondary non-biological socio-psychological effects and implications. The vignettes highlight in participants' own words: i) the potential negative implications of not addressing the psychological effects of COVID-19; ii) the lack of symptom and recovery linearity; iii) the ongoing 'lottery' of access to healthcare services; and iv) the highly variable, yet generally devastating, impacts that COVID-19 and consequent long-COVID has had across multiple facets of daily living.

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

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

Experiences of adults living with a kidney transplant-Effects on physical activity, physical function, and quality of life: A descriptive phenomenological study.

BACKGROUND: Although kidney transplantation is the best treatment for kidney failure, scarce research has examined its effects on physical activity, physical function and quality of life. OBJECTIVES: To investigate the experiences of a group of adults living with advanced kidney disease focusing on quality of life, physical activity and function and to see how findings differ in a group of kidney transplant recipients. APPROACH: Individual semi-structured interviews were conducted with adults with advanced kidney disease (n = 10; 70.5 ± 8.9 years) and adults who had received a kidney transplant (n = 10; 50.7 ± 11.5 years; transplant age: 42.7 ± 20.9 months). Interviews were transcribed verbatim, thematically analysed and composite vignettes developed. FINDINGS: Individuals with advanced kidney disease described a sense of loss and alteration to their life plans. Kidney transplant recipients reported increased freedom, independence and a return to near normality, with improved quality of life, physical activity and function compared with their pre-transplant lives. However, transplant recipients also described living with anxiety about the health of their transplant and fear it may fail. CONCLUSION: Whilst adults living with advanced kidney disease often experience a reduced quality of life, physical activity and function, kidney transplantation can help facilitate a return to pre-disease levels of physical activity, physical function and quality of life. However, transplant recipients also reported living with anxiety around their new kidney failing. This study demonstrates the variability in the lived experiences of adults living with advanced kidney disease or a kidney transplant and highlights the need for patient-centred care.

Exploring patients' experiences of the impact of dialysis therapies on quality of life and wellbeing.

BACKGROUND: When people with chronic kidney disease reach kidney failure, renal replacement therapy is usually required to improve symptoms and maintain life. Although in-centre haemodialysis is most commonly used for this purpose, other forms of dialysis are available, including home haemodialysis and peritoneal dialysis. OBJECTIVES: We aimed to explore the experiences of adults living with chronic kidney disease who were either approaching the need for dialysis or had reached kidney failure and were receiving a form of dialysis. In particular, we explored how different forms of dialysis affect their quality of life, wellbeing, and physical activity. METHODS: Individual semistructured interviews were conducted with 40 adults with kidney failure, comprising four groups (n = 10 each): those receiving in-centre haemodialysis, home haemodialysis or peritoneal dialysis, or predialysis. Interviews were transcribed verbatim, thematically analysed, and then composite vignettes were subsequently developed to present a rich narrative of the collective experiences of each group. FINDINGS: Compared with adults who were predialysis, quality of life and wellbeing improved upon initiation of their home haemodialysis or peritoneal dialysis. Conversely, minimal improvement was perceived by those receiving in-centre haemodialysis. Low physical activity was reported across all four groups, although those receiving home haemodialysis and peritoneal dialysis reported a greater desire and ability to be physically active than those in-centre. CONCLUSION: These findings highlight that dialysis modalities not requiring regular hospital attendance (i.e., home haemodialysis and peritoneal dialysis) improve independence, quality of life, wellbeing, and can facilitate a more physically active lifestyle.

Perceptions of inspiratory muscle training in adults recovering from COVID-19.

Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme. Individualised semi-structured interviews with 33 adults (29 female; 49 ± 10 years; 6-11 months post-infection) explored expectations of IMT prior to the intervention, and post intervention interviews explored perceptions of IMT and its impact on recovery. Inductive thematic analysis was used to analyse the data. IMT helped many to feel proactive in managing their symptoms and was associated with perceived improvements in respiratory symptoms, exercise and work capacity, and daily functioning. IMT was well perceived and offers significant potential for use as part of a holistic recovery programme, although it is important to consider the complex, varied symptoms of post COVID-19, necessitating an individually tailored rehabilitation approach.

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.

Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis.

OBJECTIVE: Elexacaftor/Tezacaftor/Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator with the potential to improve exercise capacity. This case series of three adolescents with CF aimed to investigate whether 6 weeks treatment with Elexacaftor/Tezacaftor/Ivacaftor could improve exercise capacity in CFTR modulator naive adolescents with CF. METHODS: Three adolescents (14.0 ± 1.4 years) with CF (FEV1 % predicted: 62.5 ± 17.1; F508del/F508del genotype) completed an exhaustive maximal cardiopulmonary exercise test on a cycle ergometer to determine peak oxygen uptake ( V ̇ $\dot{{\rm{V}}}$ O2peak ) and measure changes in gas exchange and ventilation during exercise at 6 weeks. We also analyzed wrist-worn device-based physical activity (PA) data in two of the three cases. Validated acceleration thresholds were used to quantify time spent in each PA intensity category. RESULTS: Clinically meaningful improvements in V ̇ $\dot{{\rm{V}}}$ O2peak were observed in all three cases (+17.6%, +52.4%, and +32.9%, respectively), with improvements greatest in those with more severe lung disease and lower fitness at baseline. Although lung function increased in all cases, inconsistent changes in markers of ventilatory and peripheral muscle efficiency likely suggest different mechanisms of improvement in this case group of adolescents with CF. Device-based analysis of PA was variable, with one case increasing and one case decreasing. CONCLUSION: In this case series, we have observed, for the first time, improvements in exercise capacity following 6 weeks of treatment with Elexacaftor/Tezacaftor/Ivacaftor. Improvements were greatest in the presence of more severe CF lung disease and lower aerobic fitness at baseline. The mechanism(s) responsible for these changes warrant further investigation in larger trials.

Inspiratory muscle training enhances recovery post-COVID-19: a randomised controlled trial.

BACKGROUND: Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). METHODS: 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes. RESULTS: According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

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.

The physiological and clinical importance of cardiorespiratory fitness in people with abdominal aortic aneurysm.

NEW FINDINGS: What is the topic of this review? This review focuses on the physiological impact of abdominal aortic aneurysm (AAA) on cardiorespiratory fitness and the negative consequences of low fitness on clinical outcomes in AAA. We also discuss the efficacy of exercise training for improving cardiorespiratory fitness in AAA. What advances does it highlight? We demonstrate the negative impact of low fitness on disease progression and clinical outcomes in AAA. We highlight potential mechanistic determinants of low fitness in AAA and present evidence that exercise training can be an effective treatment strategy for improving cardiorespiratory fitness, postoperative mortality and disease progression. ABSTRACT: An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta, below the level of the renal arteries, where the aorta diameter increases by >50%. As an aneurysm increases in size, there is a progressive increase in the risk of rupture, which ranges from 25 to 40% for aneurysms >5.5 cm in diameter. People with AAA are also at a heightened risk of cardiovascular events and associated mortality. Cardiorespiratory fitness is impaired in people with AAA and is associated with poor (postoperative) clinical outcomes, including increased length of hospital stay and postoperative mortality after open surgical or endovascular AAA repair. Although cardiorespiratory fitness is a well-recognized prognostic marker of cardiovascular health and mortality, it is not assessed routinely, nor is it included in current clinical practice guidelines for the management of people with AAA. In this review, we discuss the physiological impact of AAA on cardiorespiratory fitness, in addition to the consequences of low cardiorespiratory fitness on clinical outcomes in people with AAA. Finally, we summarize current evidence for the effect of exercise training interventions on cardiorespiratory fitness in people with AAA, including the associated improvements in postoperative mortality, AAA growth and cardiovascular risk. Based on this review, we propose that cardiorespiratory fitness should be considered as part of the routine risk assessment and monitoring of people with AAA and that targeting improvements in cardiorespiratory fitness with exercise training might represent a viable adjunct treatment strategy for reducing postoperative mortality and disease progression.

Exercise as an Airway Clearance Technique in people with Cystic Fibrosis (ExACT-CF): rationale and study protocol for a randomised pilot trial.

Background: Chest physiotherapy is an established cornerstone of care for people with cystic fibrosis (pwCF), but is often burdensome. Guidelines recommend at least one chest physiotherapy session daily, using various airway clearance techniques (ACTs). Exercise (with huffs and coughs) may offer an alternative ACT, however the willingness of pwCF to be randomised into a trial needs testing. The 'ExACT-CF: Exercise as an Airway Clearance Technique in people with Cystic Fibrosis' trial will test the feasibility of recruiting pwCF to be randomised to continue usual care (chest physiotherapy) or replace it with exercise ACT (ExACT) for 28-days. Secondary aims include determining the short-term clinical impact (and safety) of stopping routine chest physiotherapy and replacing it with ExACT, and effects on physical activity, sleep, mood, quality of life and treatment burden, alongside preliminary health economic measures and acceptability. Methods: Multi-centre, two-arm, randomised (1:1 allocation using minimisation), pilot trial at two sites. Fifty pwCF (≥10 years, FEV 1 >40% predicted, stable on Elexacaftor/Tezacaftor/Ivacaftor (ETI)) will be randomised to an individually-customised ExACT programme (≥once daily aerobic exercise of ≥20-minutes duration at an intensity that elicits deep breathing, with huffs and coughs), or usual care. After baseline assessments, secondary outcomes will be assessed after 28-days, with additional home lung function and exacerbation questionnaires at 7, 14 and 21-days, physical activity and sleep monitoring throughout, and embedded qualitative and health-economic components. Feasibility measures include recruitment, retention, measurement completion, adverse events, interviews exploring the acceptability of trial procedures, and a trial satisfaction questionnaire. Discussion: Co-designed with the UK CF community, the ExACT-CF pilot trial is the first multi-centre RCT to test the feasibility of recruiting pwCF stable on ETI into a trial investigating ExACT. This pilot trial will inform the feasibility, design, management, likely external validity for progression to a main phase randomised controlled trial. Registration: Clinicaltrials.gov ( NCT05482048).

Cystic fibrosis (CF) is the UK's most common inherited genetic condition and affects > 10,500 people. CF causes problems with the movement of salt and water in the body, resulting in sticky mucus building up, mostly in the lungs and gut. Thick mucus in the airways leads to repeated infections which can damage the lungs. Chest physiotherapy is routinely prescribed to keep pwCF healthy, by loosening and clearing sticky, thick mucus from the airways. However, many find it time-consuming and burdensome. People with CF (pwCF) have asked if doing exercise could have the same effect for clearing mucus. Surveys show that many pwCF have occasionally replaced chest physiotherapy with exercise for airway clearance. We also showed that many pwCF, their families, physiotherapists and doctors in the UK consider that hard exercise with huffs and coughs may be able to clear mucus from the airways. We now need to know if they would be willing to take part in research that asks some to stop chest physiotherapy and do intense exercise with huffs and coughs instead. We will study 50 pwCF (> 10 years old) for 28 days. We will ask half to continue their usual care, and half to stop chest physiotherapy and do exercise that gets them breathing deeply (with huffs and coughs) instead. We will see if people are willing to start and continue with such a study and what they think of the processes. We will also see how stopping chest physiotherapy and replacing it with exercise affects measurements of their lung function. Within the study we will talk with pwCF and members of their CF team to understand their experiences. This information will tell us whether a larger study can answer whether certain forms of exercise can safely be used as an alternative to chest physiotherapy.