Nutritional status in cystic fibrosis patients before and after initiation of triple-combination CFTR modulators

Abstract

Background: Cystic fibrosis (CF) is an inherited disease caused by a mutation that impacts multiple organs, such as the lungs, pancreas, gastrointestinal tract, and liver, affecting functions throughout the body. Nutritional treatment, including high-concentrate dietary supplements and pancreatic enzyme replacement therapy (PERT), has been a crucial part of the treatment due to CFs association with insufficient absorption and pancreatic insufficiency. Cystic fibrosis transmembrane conductance regulatory (CFTR) modulators are medications designed to target the root cause of the disease, and triple-combination CFTR modulators, combining elexacaftor/tezacaftor/ivacaftor (ETI), have been a game-changer in the treatment of CF.

Objectives: The main aim of this thesis is to investigate the effect of triple-combination CFTR modulators on nutritional status in CF patients in Western Norway. Additionally, we aim to compare the CF population in Western Norway with the general Norwegian CF population.

Methods: An observational study on 28 adult patients with CF using ETI medications was conducted during the autumn of 2023. Prospectively collected patient data was obtained from the electronic patient journal and further gathered during an in-patient study visit and follow-up by phone. Patient data encompassed dietary intake, anthropometric measurements, bioelectrical impedance analysis, handgrip strength (HGS), use of PERT to define exocrine pancreatic function, and responses to the Cystic Fibrosis Questionnaire – Revised (CFQ-R). Nordic Nutrition Recommendations (NNR) 2023 were used as a dietary reference and both the initial and revised European Society for Parenteral and Enteral Nutrition’s (ESPEN’s) guidelines on nutrition care for CF provided the basis for nutritional recommendations. Established threshold values defined by the Global Leadership Initiative on Malnutrition (GLIM) and the European Working Group on Sarcopenia in Older People (EWGSOP2) were applied to assess nutritional status. Calculated fat mass percentage (FM%) was compared to estimated ranges suggested for healthy FM% in adults. Participants’ characteristics from Haukeland University Hospital (HUH) were compared with the national CF population using data from the Norwegian CF registry.

Results: The participants’ ages spanned from 18 to 83 years, with a mean (SD) age of 35 (14) years. ETI treatment resulted in a body mass index (BMI) increase of 1.2 kg/m2, an appetite score rise from 7 to 8, and a 7 % reduction in the proportion with pancreatic insufficiency. None of the patients met the criteria for a malnutrition diagnosis according to the GLIM criteria. One female patient had an appendicular skeletal muscle mass (ASMM) below the cut-off point for sarcopenia, and one male patient exhibited average HGS below the cut-off, indicating the presence of sarcopenia. A higher proportion of patients were categorized as overweight compared to underweight. The mean FM% was towards the higher end of the range considered healthy for females and slightly above the suggested healthy range for males. The mean (SD) intake of saturated fat was 15 (7.5) E%, exceeding the recommended intake (RI). The reported intake of various food groups did not adhere to the RI levels for a balanced and healthy diet. The national CF registry data indicated that the CF population from HUH is representative of the general Norwegian CF population.

Conclusion: The current nutritional status of CF patients following ETI treatment more closely resembles that of the general non-CF population than that of the previous CF population before ETI treatment, particularly in terms of BMI, FM% and HGS. ETI treatment seems to increase body weight, heighten appetite, and improve lung function, sweat chloride levels and health-related quality of life within the CF population. While overall nutritional status has improved, proactive measures will be required to optimize the nutritional outcomes for CF patients receiving ETI treatment.