Understanding the impact of elexacaftor-tezacaftor-ivacaftor treatment on respiratory disease in people with cystic fibrosis : the change in physiotherapy treatment burden and defining pulmonary exacerbations.

Abstract

Introduction: Cystic fibrosis (CF) is the most common fatal genetic autosomal recessive disease in Caucasians. Although CF is a multisystem disorder, its respiratory complications account for the majority of morbidity and mortality. The management of lung disease in CF has developed over the years. As people with CF grow older, the amount of treatment required usually increases, and treatment burden is a major issue. Airway clearance techniques (ACTs) and nebulised mucolytics, which play a vital role in CF management, are known to be associated with the highest burden among the different treatments. The introduction of elexacaftor-tezacaftor-ivacaftor (ETI) treatment has likely led to a change in treatment needs. In addition, despite the improvement in respiratory symptoms associated with ETI, pulmonary exacerbation (PEx) remains important clinically. However, there is a lack of consensus on definitions of PEx. Aims and methods: To understand the changes in treatment burden after ETI, a semistructured qualitative interview with children, their families, and healthcare professionals were conducted to explore their opinions and attitudes toward ACTs and mucolytic nebulisers. In addition, a retrospective analysis of the data from Great North Children's Hospital (GNCH) was performed to analyse the change in physiotherapy treatment and other clinical outcomes after one year of ETI. Finally, to investigate the definitions reported for PEx, a scoping review of the literature were performed. Results: Quality of life, simplifying treatment – hopes and fears, and 'Kaftrio is a gamechanger" were three themes developed from the interviews which capture participants' experiences. From the retrospective study, a statistically significant decline in the use of ACTs and nebulised mucolytics and an improvement in exercise capacity were found. In addition, lung function and weight showed a statistically significant improvement. From the scoping review analyses, two themes were developed which highlight the PEx definitions reported in the literature. The first theme is objective – based on criteria, and the second theme is subjective- based on the clinician's judgment. Conclusion: These findings provide a comprehensive understanding of the changes after ETI in physiotherapy treatment, including ACTs, nebulised mucolytics, and exercise using multimethod designs. In addition, the scoping review findings highlighted the heterogeneity in definitions reported in the literature and helped understand the components used to define them.