Title: Assessing the effects of personalised airway clearance regimens in young people with Primary Ciliary Dyskinesia.
Funder: Health Education England

Abstract: BackgroundAirway clearance techniques (ACTs) are recommended in Chronic Suppurative Lung Conditions. One such condition is Primary Ciliary Dyskinesia (PCD) which is estimated to affect 5000 people in England. In PCD impaired mucociliary clearance causes retained mucus and airway obstruction leading to repeated infections, bronchiectasis and ultimately respiratory failure. To maintain lung health, physiotherapists advise people with PCD to complete a personalised ACT regimen twice daily at home. It is important to ensure ACT regimens are effective, but current methods of assessing the effects of ACTs are limited. This study will measure the effects of an ACT using Hyperpolarised gas Ventilation magnetic resonance imaging (Ventilation MRI), a highly sensitive tool and Proton MRI, a potentially more widely available tool as a surrogate, to measure lung ventilation. Both types of MRI are radiation free, safe and well tolerated. Ventilation MRI scans are abnormal in people with PCD even in mild disease.This study will explore how physiotherapists make decisions about ACT regimen recommendations and if providing physiotherapists with the information from the MRI changes their recommendations.PPI members initially identified research priorities and have been involved throughout this application process. Research questions What are the short-term effects of personalised ACT regimens on lung health in children and young people with PCD? How do clinicians personalise ACT regimens and is this altered by the introduction of functional imaging?AimsQuantitative: To measure lung health before and after airway clearance (compared to no intervention). To compare the findings of two outcome metrics of lung ventilation pre and post airway clearance.Mixed methods: To explore how clinicians' make decisions when reviewing and personalising ACT regimens. To investigate how clinical decision-making changes with the introduction of functional imaging of the lungs.ObjectivesQuantitative: A controlled before and after study using Ventilation MRI and Proton MRI with an ACT versus no intervention. To assess the correlation and agreement between two types of MRI.Mixed methods: Cognitive task analysis knowledge elicitation with physiotherapists to produce a concept map An experiment-like task exploring clinicians' critical decision-making at three stages: Watching an ACT regimen review. With the introduction of proton MR images. With the introduction of Ventilation MR images. The mixed methods components could be undertaken virtually if Covid-19 restrictions are imposed. Impact and disseminationThis research will provide, for the first time, accurate measurements of the short-term effects of ACTs and an understanding of how this information would influence clinical practice. I will produce a knowledge map, which ultimately will be developed into a toolkit to guide ACT personalisation. It is the first phase of a larger package aiming to optimise the effects of ACTs and maintain long-term lung health. Subsequent steps will be based on the outcomes of this project and may involve: Other conditions including Cystic Fibrosis and Bronchiectasis. Comparison of imaging guided ACTs with standard ACTs. Assessing longer-term effects of ACTs.Dissemination will target: Clinicians through appropriate posters, articles and presentations. Patients, families and wider public through a video, social media and at family days.

Lay abstract: Problem:Airway clearance techniques (ACTs) are used to move and clear mucus from the lungs in conditions where normal mucus clearance is impaired. One such condition is Primary Ciliary Dyskinesia (PCD) which affects the lungs from birth in over 5000 people in England. Without effective mucus clearance, repeated chest infections, progressive lung damage, and failure of the respiratory system is seen in people with PCD. ACTs are a major component of PCD management. The measures currently available to assess the effects of ACT regimens are limited. A National Children's PCD service was established 7 years ago and the service for adults with PCD has recently been commissioned, making this the right time for this research. This study arose from a patient and public involvement (PPI) day. PPI members set their research priority: to better understand ACTs. Solution:This study will, for the first time, measure the short-term effects of ACTs with a sensitive tool. It will use a new, safe technique; magnetic resonance imaging (MRI) to take pictures of air inside the lungs before and after an ACT.The MRI pictures can inform clinicians about patients' lung health. This study will find out how specialist physiotherapists currently decide what ACT regimen they recommend to patients and explore if providing clinicians with the information from the MRI changes their recommendations. PPI:The PCD Family Support group and young people with PCD who have had an MRI scan have shaped the aims, design, recruitment and dissemination aspects of this proposal. I will continue working with my PPI members regularly throughout this project. Study design:This study will invite clinicians working in PCD (physiotherapists, doctors and nurses) and children and young people aged 5-18 with PCD from 3 specialist centres. Children and young people with PCD:At one visit they will; Have an MRI scan Complete their usual ACT regimen with a physiotherapy review (as in clinic). This will be video recorded. Have an MRI scan At 4 hours have a final MRI scan To see if the ACT has a positive effect on the lungs over and above natural variation, a separate small group of patients will have the same scans at the same time intervals but will not complete an ACT between scans. Clinicians: I will find what specialist physiotherapists currently consider when they advise patients on their personalised ACT regimen. I will show the clinicians the video of the ACT review and ask what they would recommend. I will then show them the pictures from the MRI scans to see if this changes their recommendations.The clinician work could be done over video-calls if needed. Impact:This study will help us to understand if ACTs are having the positive effects on the health of the lungs that clinicians anticipate. It may identify if, and when, more sensitive tools, such as MRI, are needed to inform clinical decisions. It will establish how specialists advise what ACT should be used so this knowledge can be understood and shared more widely.This study will accurately measure the short-term effects of ACTs in PCD, this will be valuable knowledge for planning longer-term studies. Further research may include: Looking at other debilitating lung diseases including Cystic Fibrosis and Bronchiectasis. Comparing the effects of standard ACT advice with ACT advice guided by MRIs. Assessing the longer-term effects of ACTs with MRI. This work should also include longer-term measures such as quality of life and how often antibiotics are prescribed. The findings will be shared with: Professionals; in journals and at conferences. The PCD community and wider public; at family days, through social media and a video.

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY