ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals

E De Wachter; K De Boeck; I Sermet-Gaudelus; N J Simmonds; A Munck; L Naehrlich; J Barben; C Boyd; S J Veen; S B Carr; I Fajac; P M Farrell; E Girodon; T Gonska; W W Grody; M Jain; A Jung; E Kerem; K S Raraigh; S van Koningsbruggen-Rietschel; M D Waller; K W Southern; C Castellani; ECFS Diagnostic Network Working Group

doi:10.1016/j.jcf.2024.01.012

ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals

J Cyst Fibros. 2024 Feb 21:S1569-1993(24)00011-0. doi: 10.1016/j.jcf.2024.01.012. Online ahead of print.

Authors

E De Wachter¹, K De Boeck², I Sermet-Gaudelus³, N J Simmonds⁴, A Munck⁵, L Naehrlich⁶, J Barben⁷, C Boyd⁸, S J Veen⁸, S B Carr⁹, I Fajac¹⁰, P M Farrell¹¹, E Girodon¹², T Gonska¹³, W W Grody¹⁴, M Jain¹⁵, A Jung¹⁶, E Kerem¹⁷, K S Raraigh¹⁸, S van Koningsbruggen-Rietschel¹⁹, M D Waller²⁰, K W Southern²¹, C Castellani²²; ECFS Diagnostic Network Working Group

Affiliations

¹ Cystic Fibrosis Center, Pediatric Pulmonology department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: elke.dewachter@uzbrussel.be.
² Department of Pediatrics, University of Leuven, Leuven, Belgium.
³ INSERM U1151, Institut Necker Enfants Malades, Paris, France; Université de Paris, Paris, France; Centre de référence Maladies Rares, Mucoviscidose et maladies apparentées. Hôpital Necker Enfants malades, Paris, France.
⁴ Adult Cystic Fibrosis Centre, Royal Brompton Hospital and Imperial College, London, UK.
⁵ Paediatric Cystic Fibrosis centre, Hôpital Necker Enfants Malades, AP-HP Paris, France.
⁶ Department of Pediatrics, Justus-Liebig-University Giessen, Germany.
⁷ Paediatric Pulmonology & CF Centre, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
⁸ Patient representative.
⁹ Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, and Imperial College, London, UK.
¹⁰ Assistance Publique-Hôpitaux de Paris, Thoracic Department and National Cystic Fibrosis Reference Centre, Cochin Hospital, 75014 Paris, France; Université Paris Cité, Inserm U1016, Institut Cochin, 75014 Paris, France.
¹¹ Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
¹² Service de Médecine Génomique des Maladies de Système et d'Organe, APHP.Centre - Université de Paris Cité, Hôpital Cochin, Paris, France.
¹³ Division of Pediatric Gastroenterology, Hepatology, Nutrition, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Program of Translational Medicine, Research institute, Hospital for Sick Children, Toronto, Canada.
¹⁴ Departments of Pathology & Laboratory Medicine, Pediatrics, and Human Genetics, UCLA School of Medicine, Los Angeles, California 90095-1732, USA.
¹⁵ Northwestern University Feinberg School of Medicine, Pulmonary Critical Care, Chicago, Illinois, United States.
¹⁶ University Children`s Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
¹⁷ Department of Pediatrics and CF Center, Hadassah Hebrew University medical Center, Jerusalem, Israel.
¹⁸ Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
¹⁹ CF Center Cologne, Children´s Hospital, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
²⁰ Department of Adult Cystic Fibrosis and Respiratory Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom; Centre for Human & Applied Physiological Sciences, King's College London, London, United Kingdom.
²¹ Department of Women's and Children's Health, University of Liverpool, Alder Hey Children's Hospital, Liverpool, UK.
²² IRCCS Istituto Giannina Gaslini, Cystic Fibrosis Center, Genoa, Italy.

PMID: 38388234
DOI: 10.1016/j.jcf.2024.01.012

Abstract

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.

Keywords: CF-registry; CFTR; CFTR-RD; CFTR-related disorder; CRMS/CFSPID; Clinical trials, genetic counseling; Cystic fibrosis; Genetics.