Stephanie Bui
Laurence Delhaes2,3
Gael Dournes
Philippe Reix
Michael John Fayon- 1Paediatric Cystic Fibrosis Reference Center (CRCM), Bordeaux University Hospital, Hôpital Pellegrin-Enfants, Bordeaux, France
- 2Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, Bordeaux University Hospital, Bordeaux, France
- 3Service de Parasitologie-Mycologie, UMR 12 19, U1045, Bordeaux University Hospital, Bordeaux, France
- 4Service d’Imagerie Thoracique et Cardiovasculaire, Bordeaux University Hospital, Bordeaux, France
- 5Lyon University Hospital, Hospices Civils de Lyon, Lyon, France
- 6Paediatric Cystic Fibrosis Reference Center (CRCM), UMR 5558, Centre National de Recherche Scientifique (CNRS), Lyon, France
Editorial on the Research Topic
New insights into caring for pediatric patients with cystic fibrosis
Cystic fibrosis (CF) is a rare and severe inherited autosomal recessive disease with more than 2,000 mutations identified in registries around the world. CF is related to mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes the CFTR epithelial ion channel involved in chloride and bicarbonate transport leading to impaired mucus hydration and clearance (1–3). The reduced functional protein at the cell surface is characterised by multiple exocrinopathies including lung involvement due to thick dehydrated bronchial secretions, favouring chronic and acute infections and inflammation (1). Pulmonary exacerbations occur frequently and are associated with poor nutritional status, leading to progressive lung function decline and death in people with CF (pwCF) (4, 5). To prevent such morbidity and mortality, standards of care rely on multidisciplinary team management and trimonthly follow-up (6–8).
The present special issue on CF focuses on new insights into CF care. One review shows that although neonatal screening is set up in most countries, physicians should be aware that CF should also be evoked based on non-specific clinical signs.
Furthermore, until recently, for most pwCF, management relied mainly on symptomatic therapies (physiotherapy, mucolytics, and pancreatic enzymes, etc.) (6, 8). Such treatments have shown their ability to slow down the progression of CF and enhance life expectancy (9). In the last few years, new therapeutic approaches for treating CF have been developed aiming at restoring CFTR function in a wider proportion of pwCF, notably those bearing at least one F508del CFTR mutation (around 70% to 80% of pwCF). F508del mutation is responsible for processing and trafficking defects in the mutated F508del CFTR protein, leading to its degradation before it reaches the epithelial cell surface (1–3). Modulators generally associate one, two, or three CFTR correctors, which enhance the cellular protein processing and trafficking, and a potentiator, which increases the channel-opening probability (1, 4). At the present time, triple combination therapy associating two correctors (elexacaftor and tezacaftor) and a potentiator (ivacaftor) is available for a large proportion of pwCF upwards of 6 years of age. These new molecules have revolutionised CF prognosis, decreased treatment burden, and improved daily quality of life (10, 11).
This issue also includes a study on the evolution of nutritional intake in children with CF (cwCF), in particular after administration of the first class of modulators [lumacaftor–ivacaftor (LI)] in F508del homozygous patients. Regarding the pulmonary outcome, which is slightly improved under LI (12–14), assessments now include artificial intelligence to help in deciphering respiratory imaging structural changes.
Finally, regarding the real-life cohorts for the most recent modulator (elexacaftor–tezacaftor–ivacaftor: ETI), who have demonstrated dramatic improvement in their lung function and nutritional status (10, 11), we include a paper describing the validity and feasibility of telehealth home monitoring with spirometric connected devices to help multidisciplinary teams follow up the disease in this new therapeutic era.
Although we have experienced dramatic improvements in the diagnosis, management, and follow-up of CF, the next steps will be to diagnose and treat all patients with a personalised medicine approach, including those without mutations currently eligible for modulator therapies. Such therapies should also be made available to more and more pwCF throughout the world.
Author contributions
SB has contributed as the editor, LD, GD, PR, MF have contributed as co-editors. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Bui S, Macey J, Fayon M, Bihouée T, Burgel PR, Colomb V, et al. Nouvelles thérapeutiques ciblant le canal chlorure dans la mucoviscidose. Arch Pédiatrie. (2016) 23(12):12S47–53. doi: 10.1016/S0929-693X(17)30062-3
2. Hanrahan JW, Sampson HM, Thomas DY. Novel pharmacological strategies to treat cystic fibrosis. Trends Pharmacol Sci. (2013) 34(2):119–25. doi: 10.1016/j.tips.2012.11.006
3. Lubamba B, Dhooghe B, Noel S, Leal T. Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy. Clin Biochem. (2012) 45(15):1132–44. doi: 10.1016/j.clinbiochem.2012.05.034
4. De Boeck K. Cystic fibrosis in the year 2020: a disease with a new face. Acta Paediatr. (2020) 109(5):893–9. doi: 10.1111/apa.15155
5. De Boeck K, Zolin A. Year to year change in FEV1 in patients with cystic fibrosis and different mutation classes. J Cyst Fibros. (2017) 16(2):239–45. doi: 10.1016/j.jcf.2016.09.009
6. Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, et al. European Cystic fibrosis society standards of care: best practice guidelines. J Cyst Fibros. (2014) 13:S23–42. doi: 10.1016/j.jcf.2014.03.010
7. Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, et al. Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation. J Pediatr. (2017) 181:S4–15.e1. doi: 10.1016/j.jpeds.2016.09.064
8. Turck D, Braegger CP, Colombo C, Declercq D, Morton A, Pancheva R, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr. (2016) 35(3):557–77. doi: 10.1016/j.clnu.2016.03.004
9. Stephenson AL, Stanojevic S, Sykes J, Burgel PR. The changing epidemiology and demography of cystic fibrosis. Presse Médicale. (2017) 46(6):e87–95. doi: 10.1016/j.lpm.2017.04.012
10. Mall MA, Brugha R, Gartner S, Legg J, Moeller A, Mondejar-Lopez P, et al. Efficacy and safety of elexacaftor/tezacaftor/ivacaftor in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function mutation: a phase 3b, randomized, placebo-controlled study. Am J Respir Crit Care Med. (2022) 206(11):1361–9. doi: 10.1164/rccm.202202-0392OC
11. Nichols DP, Paynter AC, Heltshe SL, Donaldson SH, Frederick CA, Freedman SD, et al. Clinical effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: a clinical trial. Am J Respir Crit Care Med. (2022) 205(5):529–39. doi: 10.1164/rccm.202108-1986OC
12. Bui S, Masson A, Enaud R, Roditis L, Dournes G, Galode F, et al. Long-term outcomes in real life of lumacaftor–ivacaftor treatment in adolescents with cystic fibrosis. Front Pediatr. (2021) 9:744705. doi: 10.3389/fped.2021.744705
13. Burgel PR, Munck A, Durieu I, Chiron R, Mely L, Prevotat A, et al. Real-life safety and effectiveness of lumacaftor–ivacaftor in patients with cystic fibrosis. Am J Respir Crit Care Med. (2020) 201(2):188–97. doi: 10.1164/rccm.201906-1227OC
Keywords: cystic fibrosis, standard of care, modulators, telehealth, artificial inteligence, nutritional status, newborn screening (NBS)
Citation: Bui S, Delhaes L, Dournes G, Reix P and Fayon MJ (2023) Editorial: New insights into caring for pediatric patients with cystic fibrosis. Front. Pediatr. 11:1243496. doi: 10.3389/fped.2023.1243496
Received: 20 June 2023; Accepted: 26 June 2023;
Published: 9 August 2023.
Edited and Reviewed by: Anne B. Chang, Charles Darwin University, Australia
© 2023 Bui, Delhaes, Dournes, Reix and Fayon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Stephanie Bui stephanie.bui@chu-bordeaux.fr