Award Title: ExACT-CF: Exercise as an Airway Clearance Technique in people with Cystic Fibrosis – A randomised pilot trial
Funder: Department of Health and Social Care

Abstract: Background: Routine chest physiotherapy, which aims to loosen, mobilise and expectorate airway secretions, is a cornerstone of clinical care for people with cystic fibrosis (CF). Guidelines advise at least one session daily, choosing from various modalities that exist under the umbrella term airway clearance techniques (ACT). However, many people with CF find ACT time-consuming and burdensome. Unsurprisingly, therefore, the question "can exercise replace chest physiotherapy" was assigned a top 10 research priority by people with CF, alongside reducing treatment burden. There is growing evidence that exercise (with coughs and huffs) may be an alternative to chest physiotherapy, however the willingness of people with CF to be randomised into such a trial and their experiences need testing.  Aims and Objectives: We will assess the feasibility of recruiting people with CF into a trial where they will be randomised to either continue usual care (chest physiotherapy) or to stop this and replace it with exercise as an ACT (ExACT). This randomised pilot trial will inform the design, management, and delivery of a future larger randomised, controlled, non-inferiority trial. Key objectives include: assessing feasibility and acceptability of methods of participant recruitment and retention; assessing feasibility of quantitative and qualitative (outcome and process) data collection; exploring intervention engagement; and refining methodology for the definitive trial. We will measure short-term (28-days) clinical impact of stopping routine chest physiotherapy.   Methods: We will conduct a two-arm randomised pilot trial, with people with CF >12 years (n=50). The trial will include assessments at baseline and following 28-days of usual care or ExACT, with additional home lung function and exacerbation questionnaires at 1, 7, 14 and 21-days, and an embedded qualitative component. Data collection methods will include those proposed for a definitive trial, e.g., research database logging chest physiotherapy, lung function in clinic and at home, wrist worn physical activity monitoring and questionnaires evaluating quality of life, treatment burden, and mood; and qualitative interviews exploring intervention use, acceptability and fidelity. Feasibility measures include reports on recruitment, retention, measurement completion, adverse events, interviews exploring the acceptability of trial procedures to people with CF and their clinical teams, and a trial satisfaction questionnaire. Early signals regarding the clinical impact and safety of stopping chest physiotherapy will be measured using lung clearance index and monitoring processes, as well as preliminary health economics analysis.   Timelines for delivery: The proposed work schedule is 18-months. Months 0-5 comprise the study set-up phase, protocol development and acquiring regulatory approvals. Months 6-11 comprise recruitment and the pilot trial. During the final stage (months 15-18) we will use the findings of the pilot trial to develop the main phase ExACT-CF trial protocol, prepare a grant application, and disseminate our study findings; involving our PPI group throughout.   Anticipated impact and dissemination: Study findings will be shared with stakeholders; healthcare professionals, people with CF and their families, national (UK CF Trust) and international (CF Warriors) CF charities. Dissemination will occur via social media, peer-reviewed publications, conference presentations and virtual educational events. This project will inform a larger evaluation (definitive trial).

Lay Abstract: Cystic fibrosis (CF) is the UK s most common inherited genetic condition and affects more than 10,500 people. The disease 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, over time, damage the lungs. Chest physiotherapy is prescribed to loosen and clear sticky thick mucus from the airways and so to help to reduce lung infection.   Chest physiotherapy is a routine treatment to keep people with CF healthy. However, many say it is time-consuming and a burden. People with CF have asked if doing exercise could have the same effect as chest physiotherapy sessions for helping clear mucus. Exercise could be more enjoyable and less burdensome. Through a recognised priority setting partnership, the CF community recently ranked research to  reduce the burden of their care  and answer  whether exercise can replace chest physiotherapy , as their number 1 and 7 priorities. Surveys show that many people with CF have occasionally chosen to replace chest physiotherapy with exercise for airway clearance, and we recently confirmed this through a UK-wide survey. We now need to know if they would be willing to take part in research that asks some to stop chest physiotherapy and to exercise (with coughs and huffs) instead.   New medicine (modulators) have recently become available for many people with CF, bringing dramatic improvements in their health. Some people who have started modulators are considering whether they can reduce or stop treatments – including chest physiotherapy. So, we need to know the effects of stopping chest physiotherapy and determine if exercise can be used instead - our study aims to understand this. Our recent survey in people with CF, their families, physiotherapists and doctors, showed us that many consider hard exercise with coughs and huffs to be able to clear mucus from the airways.   We will study 50 people with CF (>12 years old) for 28-days. We will ask half of them to continue their usual care, and half to stop chest physiotherapy and do exercise that gets them breathing deeply (with coughs and huffs) instead. We will see if people are willing to start and continue with such a study and what they think of the study 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 people with CF and members of their CF team to understand their experiences. This information will tell us whether a larger study can answer the question of whether certain forms of exercise can safely be used as an alternative to chest physiotherapy.

Research Activity Codes: 6.7 PHYSICAL
Health Categories: CONGENITAL DISORDERS