Birimberg L. and Massip E.: Gastrointestinal benefits from highly effective modulator therapy in CF

Once again it’s been an unfair contest here in the ESPGHAN podcast-recording studio, little me on one side, on the other Dr. Etna Masip Simó of Valencia and Dr. Liron Birimberg-Schwartz of Jerusalem – you listeners have ringside seats for the battle, which of course Dr. Birimberg-Schwartz and Dr. Masip won without so much as trying. They are experts in the nutritional dysregulation that results from cystic fibrosis, you see… Dr. Masip trained in Valencia and Catalonia, and now in Valencia heads the paediatric cystic-fibrosis unit at La Fe University and Polytechnic Hospital. Dr. Birimberg-Schwartz trained in Jerusalem and in Toronto, at the Hospital for Sick Children, and now, back in Jerusalem at Hadassah Medical Center, attends patients and conducts research into cystic fibrosis using organoids in culture. The prospects for children with cystic fibrosis have been substantially improved by the complementary deployment of agents that alleviate dysfunction of variant cystic fibrosis transmembrane-conductance regulator (CFTR), with elexacaftor and tezacaftor shifting CFTR within the cell membrane to sites permissive for CFTR activity and ivacaftor potentiating that activity. Unfortunately, efficacy of the elexacaftor–tezacaftor–ivacaftor (ETI) combination in modulating CFTR activity differs from variant to variant, but for many patients ETI appears to have improved both ventilatory and digestive quality of life. In those patients for whom ETI means better nutrition, what are the consequences of its availability for the need to re-think recommendations for their care, particularly regarding dietary composition, growth monitoring, and follow-up protocols? Beyond weight gain, what real-life evidence supports the impression that gastrointestinal symptoms and inflammation are ameliorated in paediatric cystic-fibrosis patients (adolescents included) treated with ETI? Finally, does ETI therapy modify the natural course of cystic-fibrosis–related liver disease in children, and might it reduce the need for routine hepatologic surveillance in selected patients? Dr. Birimberg-Schwartz and Dr. Masip, as was to be expected, carry the day. Enjoy listening to them and enjoy their expertise! LiteratureMainz JG et al. Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and calprotectin over one year of treatment with elexacaftor–tezacaftor–ivacaftor in people with CF aged ≥12 years – The RECOVER study. J Cyst Fibros 2024 May; 23(3):474–480. doi: 10.1016/j.jcf.2023.10.001. Epub 2023 Oct 7. PMID: 37806792Terlizzi V et al. Effect of elexacaftor–tezacaftor–ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis. J Cyst Fibros 2025 Jan 12:S1569-1993(24)01861-7. doi: 10.1016/j.jcf.2024.12.010. Online ahead of print. PMID: 39800644Wilschanski M et al. ESPEN–ESPGHAN–ECFS guideline on nutrition care for cystic fibrosis. Clin Nutr 2024 Feb; 43(2):413–445. doi: 10.1016/j.clnu.2023.12.017. Epub 2023 Dec 27. PMID: 38169175Dr. Masip & Dr. Birimberg-Schwartz’s favourite song: The Beatles – Here Comes the Sun ESPGHAN favourite Songs can be found on Spotify: Spotify Playlist