Cystic fibrosis

French national reference center for cystic fibrosis and conditions linked to a CFTR abnormality

logo CRMR MucoviscidoseThe reference center for cystic fibrosis and conditions linked to a CFTR abnormality at Necker hospital monitors a cohort of 250 patients with cystic fibrosis and related forms, making it one of the largest pediatric centers in the world.
Care emphasizes on outpatient care and benefits from a well-honed program, in connection with the therapeutic education transversal unit (UTET), home assignments and therapeutic education for families. It is backed by innovative research, both translational and fundamental, carried out within the Necker-Enfants malades institute (INEM), directed by Pr Sermet with recurrent national, European and North American funding.

Three more specific aspects are developed:

  • expertise in preparing patients with respiratory failure for lung transplantation;
  • the assessment of patients referred for suspected cystic fibrosis in whom the diagnosis cannot be concluded on conventional genetic arguments;
  • significant research activity.

Medical
team

Pr Isabelle Sermet-Gaudelus
MD, PhD

Contact us
 

Consultations
At the reception when you are on the spot

Phone. +33 1 44 49 57 44

> Send an email

Functional respiratory examinations

Phone. +33 1 44 49 50 47

> Send an email

In case of emergency

Patients with cystic fibrosis and related forms

Patients with suspected cystic fibrosis

Vignette vidéo qu'est ce que la mucoviscidose

Patients with respiratory failure awaiting lung transplantation

The preparation of these patients is based on a unique multidisciplinary expertise optimizing the preparation for lung transplantation and ensuring national recruitment, combining :

  • care in the pediatric pneumoallergology department and the cystic fibrosis functional unit ;
  • a transversal unit for the care of children in non-invasive ventilation ;
  • the exploration of pulmonary hypertension in pediatric cardiology ;
  • various pediatric specialty services for the care of multisystemic patients ;
  • transversal units allowing symptomatic care (nutrition, infectious diseases, endocrinology, psychiatry, diabetology, exercise re-training, etc.) and facilitating outpatient monitoring (transversal therapeutic education unit) ;
  • a pediatric resuscitation and continuing care service for decompensating patients ;
  • a pediatric surgery department with thoracic specialization ;
  • a technical platform combining endobronchial fibroscopy, associated histological expertise, pulmonary imaging.

The multidisciplinary care of patients registered or soon registered on the transplant list is provided by various programs :

  • respiratory rehabilitation (24 hours a day on-call physiotherapists, exercise reconditioning, implementation if necessary of non-invasive ventilation) ;
  • nutritional rehabilitation (enteral and / or parenteral nutrition in collaboration with the pediatric nutritional unit) ;
  • adaptation of the anti-infectious strategy in collaboration with the microbiology department and the mobile infectious disease unit ;
  • care of painful cases ; supportive psychotherapy and body therapy ;
  • establishment of a network with relay centers.

Since January 2019, the Necker teams have been providing pediatric lung transplantation and post-transplant patient monitoring. This involves cardiac and thoracic surgery, medical resuscitation, the pediatric pneumoallergology department and the cystic fibrosis functional unit.

En savoir +

The medical follow-up of patients followed at the cystic fibrosis functional unit is provided by :

  • Pr Isabelle Sermet-Gaudelus,
  • Dr Muriel Le Bourgeois,
  • Dr Frédérique Chedevergne
  • Dr Céline Bailly.

Each doctor is a referent for his outpatients. Doctors Chedevergne and Bailly are referents for the activity of the day hospital, Professor Sermet-Gaudelus for traditional hospitalization and the care of patients awaiting pediatric lung transplantation.

Paramedical monitoring is provided by :

  • Aline Lustre, coordinating nurse specifically dedicated to the cystic fibrosis resource and competence center (CRCM) and Marlène Clairicia Pierre-Joseph, training nurse at the child home treatment training center (CFTDE) ;
  • Caroline Grapin, physiotherapist specifically dedicated to the CRCM and Hélène Avril, physiotherapist from the functional rehabilitation department ;
  • Maya Kirszenbaum, psychologist specifically dedicated to the CRCM ;
  • Nathalie Nguyen-Lekhaj, secretary ;
  • a dietitian from the dietetic service pool ;
  • a social worker from the pediatric pneumo-allergology service ;
  • Déborah Fuchs, medico-sports educator in the functional rehabilitation service.

Therapeutic education pathway for a child with cystic fibrosis and his parents, from screening to adulthood

The research activity is supported by the local association « Mucoviscidose – ABCF2 » intended to promote research in cystic fibrosis.

Fundamental research takes place within a labeled research structure: Inserm U 1511, Institut Necker-Enfants malades. Faculty of medicine, Paris V. directed by Pr Sermet.

The research program focuses on the involvement of the CFTR protein in normal and pathological lungs.

The main lines of research are:

  • research of CFTR partner proteins, allowing the identification of signaling pathways linked to CFTR dysfunction and creating new therapeutic targets ;
  • the study of unconventional CFTR secretion pathways and research of innovative cell therapy pathways ;
  • involvement of CFTR in other respiratory epithelial pathologies (COPD) and in abnormalities of lung development ;
  • personalized therapy program for cystic fibrosis and related forms: research of new modulators of CFTR, development of tools to establish the effectiveness of these molecules; development of specific models from primary cultures of nasal cells and organoids derived from intestinal and respiratory tissues of patients. Application of these tools for a preclinical evaluation of new CFTR modulating therapies and identification of factors of phenotypic heterogeneity and therapeutic response.

This program is supported by recurrent funding: H2020 “PRO-CF-MED ; ANR 2014 ; recurrent French and American associative funding. Industrial financing.

Translational research is being carried out in conjunction with the Clinical Investigation Center (CIC) and is based on extensive therapeutic trial activity for new CFTR modulators.

  • Fungal infection UD
  • Rare disease IUD
  • Pediatric pulmonology IUD
  • Pediatric infectious disease IUD
  • Palliative care IUD
  • Junior training in pediatrics

2020

[Focus on cystic fibrosis].
Isabelle Sermet-Gaudelus, Marlène Clairicia Pierre-Joseph, Aline Lustre, Annabelle Voltine, Hélène Roze
Rev Infirm, 2020 Jan, PMID: 32146956 DOI: 10.1016/j.revinf.2019.12.007

A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials.
G Taccetti, M Denton, K Hayes, ECFS-CTN Microbiology Group; P Drevinek, I Sermet-Gaudelus
J Cyst Fibros, 2020 Jan, PMID: 31526710 DOI: 10.1016/j.jcf.2019.08.014

Insights into the variability of nasal potential difference, a biomarker of CFTR activity.
Spyridoula Kyrilli, Theophraste Henry, Michael Wilschanski, Isabelle Fajac, Jane C Davies, Jean-Philippe Jais, Isabelle Sermet-Gaudelus
J Cyst Fibros, 2020 Jul, PMID: 31699569 DOI: 10.1016/j.jcf.2019.09.015

Current and future diagnosis of cystic fibrosis: Performance and limitations.
T Bienvenu, T Nguyen-Khoa
Arch Pediatr, 2020 Feb, PMID: 32172931 DOI: 10.1016/S0929-693X(20)30046-4

Mucoviscidosis: fisiopatología, genética, aspectos clínicos y terapéuticos
S Noël, I Sermet-Gaudelus
EMC Pediatr, 2020 Mar, PMID: 32288518 PMCID: PMC7147672 DOI: 10.1016/S1245-1789(20)43427-4

Urinary Exosomes of Patients with Cystic Fibrosis Unravel CFTR-Related Renal Disease.
Sebastien Gauthier, Iwona Pranke, Vincent Jung, Loredana Martignetti, Véronique Stoven, Thao Nguyen-Khoa, Michaela Semeraro, Alexandre Hinzpeter, Aleksander Edelman, Ida Chiara Guerrera, Isabelle Sermet-Gaudelus
Int J Mol Sci, 2020 Sep 10, PMID: 32927759 PMCID: PMC7554933 DOI: 10.3390/ijms21186625

Suppressing  »nonsense » in cystic fibrosis.
Alexandre Hinzpeter, Isabelle Sermet-Gaudelus, David N Sheppard
J Physiol, 2020 Feb, PMID: 31869855 DOI: 10.1113/JP279267

Impact of COVID-19 on people with cystic fibrosis.
Carla Colombo, Pierre-Régis Burgel, Silvia Gartner, Silke van Koningsbruggen-Rietschel, Lutz Naehrlich, Isabelle Sermet-Gaudelus, Kevin W Southern
Lancet Respir Med, 2020 May, PMID: 32304639 PMCID: PMC7159857 DOI: 10.1016/S2213-2600(20)30177-6

2019

Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis.
Simonin J, Bille E, Crambert G, Noel S, Dreano E, Edwards A, Hatton A, Pranke I, Villeret B, Cottart CH, Vrel JP, Urbach V, Baatallah N, Hinzpeter A, Golec A, Touqui L, Nassif X, Galietta LJV, Planelles G, Sallenave JM, Edelman A, Sermet-Gaudelus I.
Sci Rep. 2019 Apr 24;9(1):6516. doi: 10.1038/s41598-019-42751-4. PMID:31019198

Mycobacterium bolletii Lung Disease in Cystic Fibrosis.
Rollet-Cohen V, Roux AL, Le Bourgeois M, Sapriel G, El Bahri M, Jais JP, Heym B, Mougari F, Raskine L, Véziris N, Gaillard JL, Sermet-Gaudelus I.
Chest. 2019 Aug;156(2):247-254. doi: 10.1016/j.chest.2019.03.019. Epub 2019 Mar 29. PMID:30935892

Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine.
Pranke I, Golec A, Hinzpeter A, Edelman A, Sermet-Gaudelus I.
Front Pharmacol. 2019 Feb 27;10:121. doi: 10.3389/fphar.2019.00121. eCollection 2019. Review. PMID:30873022

Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence.
Tan X, Coureuil M, Ramond E, Euphrasie D, Dupuis M, Tros F, Meyer J, Nemazanyy I, Chhuon C, Guerrera IC, Ferroni A, Sermet-Gaudelus I, Nassif X, Charbit A, Jamet A.
Clin Infect Dis. 2019 Feb 7. doi: 10.1093/cid/ciz106. PMID:30753350

Predictive factors for lumacaftor/ivacaftor clinical response.
Masson A, Schneider-Futschik EK, Baatallah N, Nguyen-Khoa T, Girodon E, Hatton A, Flament T, Le Bourgeois M, Chedevergne F, Bailly C, Kyrilli S, Achimastos D, Hinzpeter A, Edelman A, Sermet-Gaudelus I.
J Cyst Fibros. 2019 May;18(3):368-374. doi: 10.1016/j.jcf.2018.12.011. Epub 2018 Dec 28. PMID:30595473

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis.
Sermet-Gaudelus I, Clancy JP, Nichols DP, Nick JA, De Boeck K, Solomon GM, Mall MA, Bolognese J, Bouisset F, den Hollander W, Paquette-Lamontagne N, Tomkinson N, Henig N, Elborn JS, Rowe SM.
J Cyst Fibros. 2019 Jul;18(4):536-542. doi: 10.1016/j.jcf.2018.10.015. Epub 2018 Nov 19. PMID:30467074

2018

Increased expression of ATP12A proton pump in cystic fibrosis airways.
Scudieri P, Musante I, Caci E, Venturini A, Morelli P, Walter C, Tosi D, Palleschi A, Martin-Vasallo P,Sermet-Gaudelus I, Planelles G, Crambert G, Galietta LJ.
JCI Insight. 2018 Oct 18;3(20). pii: 123616. doi: 10.1172/jci.insight.123616.
PMID:30333310

Structure-guided combination therapy to potently improve the function of mutant CFTRs.
Veit G, Xu H, Dreano E, Avramescu RG, Bagdany M, Beitel LK, Roldan A, Hancock MA, Lay C, Li W, Morin K, Gao S, Mak PA, Ainscow E, Orth AP, McNamara P, Edelman A, Frenkiel S, Matouk E, Sermet-Gaudelus I, Barnes WG, Lukacs GL.
Nat Med. 2018 Nov;24(11):1732-1742. doi: 10.1038/s41591-018-0200-x. Epub 2018 Oct 8. PMID:30297908

Correction to: In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study.
Sermet-Gaudelus I, Renouil M, Fajac A, Bidou L, Parbaille B, Pierrot S, Davy N, Bismuth E, Reinert P, Lenoir G, Lesure JF, Rousset JP, Edelman A.
BMC Med. 2018 Aug 25;16(1):159. doi: 10.1186/s12916-018-1138-z. PMID:30143037

Comparative proteomics of respiratory exosomes in cystic fibrosis, primary ciliary dyskinesia and asthma.
Rollet-Cohen V, Bourderioux M, Lipecka J, Chhuon C, Jung VA, Mesbahi M, Nguyen-Khoa T, Guérin-Pfyffer S, Schmitt A, Edelman A, Sermet-Gaudelus I, Guerrera IC.
J Proteomics. 2018 Aug 15;185:1-7. doi: 10.1016/j.jprot.2018.07.001. Epub 2018 Jul 3. PMID:30032860

ECFS best practice guidelines: the 2018 revision.
Castellani C, Duff AJA, Bell SC, Heijerman HGM, Munck A, Ratjen F, Sermet-Gaudelus I, Southern KW, Barben J, Flume PA, Hodková P, Kashirskaya N, Kirszenbaum MN, Madge S, Oxley H, Plant B, Schwarzenberg SJ, Smyth AR, Taccetti G, Wagner TOF, Wolfe SP, Drevinek P.
J Cyst Fibros. 2018 Mar;17(2):153-178. doi: 10.1016/j.jcf.2018.02.006. Epub 2018 Mar 3. Review. PMID:29506920

Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons.
Pranke I, Bidou L, Martin N, Blanchet S, Hatton A, Karri S, Cornu D, Costes B, Chevalier B, Tondelier D, Girodon E, Coupet M, Edelman A, Fanen P, Namy O, Sermet-Gaudelus I, Hinzpeter A.
ERJ Open Res. 2018 Feb 23;4(1). pii: 00080-2017. doi: 10.1183/23120541.00080-2017. eCollection 2018 Jan. Erratum in: ERJ Open Res. 2018 Jul 13;4(3):. PMID:29497617

Cis variants identified in F508del complex alleles modulate CFTR channel rescue by small molecules.
Baatallah N, Bitam S, Martin N, Servel N, Costes B, Mekki C, Chevalier B, Pranke I, Simonin J, Girodon E, Hoffmann B, Mornon JP, Callebaut I, Sermet-Gaudelus I, Fanen P, Edelman A, Hinzpeter A.
Hum Mutat. 2018 Apr;39(4):506-514. doi: 10.1002/humu.23389. Epub 2018 Jan 16.
PMID:29271547

Multifocal fixed drug eruption to ceftazidime in a child with cystic fibrosis.
Ben Mansour A, Bellon N, Frassati-Biaggi A, Sermet-Gaudelus I, Ponvert C, de Blic J, Lezmi G.
Pediatr Allergy Immunol. 2018 Feb;29(1):115-117. doi: 10.1111/pai.12829. Epub 2017 Nov 28. No abstract available.
PMID:29047164

Pseudomonas aeruginosa LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator-IL-6-antimicrobial-repair pathway.
Saint-Criq V, Villeret B, Bastaert F, Kheir S, Hatton A, Cazes A, Xing Z, Sermet-Gaudelus I, Garcia-Verdugo I, Edelman A, Sallenave JM.
Thorax. 2018 Jan;73(1):49-61. doi: 10.1136/thoraxjnl-2017-210298. Epub 2017 Aug 8. PMID:28790180

2017

Guidelines for the clinical management and follow-up of infants with inconclusive cystic fibrosis diagnosis through newborn screening.
Sermet-Gaudelus I, Brouard J, Audrézet MP, Couderc Kohen L, Weiss L, Wizla N, Vrielynck S, LLerena K, Le Bourgeois M, Deneuville E, Remus N, Nguyen-Khoa T, Raynal C, Roussey M, Girodon E.
Arch Pediatr. 2017 Dec;24(12):e1-e14. doi: 10.1016/j.arcped.2017.07.015. Epub 2017 Nov 22. PMID:29174009

Omalizumab treatment for allergic bronchopulmonary aspergillosis in young patients with cystic fibrosis.
Perisson C, Destruys L, Grenet D, Bassinet L, Derelle J, Sermet-Gaudelus I, Thumerelle C, Prevotat A, Rosner V, Clement A, Corvol H.
Respir Med. 2017 Dec;133:12-15. doi: 10.1016/j.rmed.2017.11.007. Epub 2017 Nov 10. PMID:29173443

The suppression of premature termination codons and the repair of splicing mutations in CFTR.
Oren YS, Pranke IM, Kerem B, Sermet-Gaudelus I.
Curr Opin Pharmacol. 2017 Jun;34:125-131. doi: 10.1016/j.coph.2017.09.017. Epub 2017 Nov 10. Review. PMID:29128743

Pain is an underestimated symptom in cystic fibrosis.
Masson A, Kirszenbaum M, Sermet-Gaudelus I.
Curr Opin Pulm Med. 2017 Nov;23(6):570-573. doi: 10.1097/MCP.0000000000000427. Review. PMID:28806187

Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators.
Pranke IM, Hatton A, Simonin J, Jais JP, Le Pimpec-Barthes F, Carsin A, Bonnette P, Fayon M, Stremler-Le Bel N, Grenet D, Thumerel M, Mazenq J, Urbach V, Mesbahi M, Girodon-Boulandet E, Hinzpeter A, Edelman A, Sermet-Gaudelus I.
Sci Rep. 2017 Aug 7;7(1):7375. doi: 10.1038/s41598-017-07504-1. PMID:28785019

A multiple reader scoring system for Nasal Potential Difference parameters.
Solomon GM, Liu B, Sermet-Gaudelus I, Fajac I, Wilschanski M, Vermeulen F, Rowe SM.
J Cyst Fibros. 2017 Sep;16(5):573-578. doi: 10.1016/j.jcf.2017.04.011. Epub 2017 Apr 29. PMID:28465124

[Management of infants whose diagnosis is inconclusive at neonatal screening for cystic fibrosis].
Sermet-Gaudelus I, Brouard J, Audrézet MP, Couderc Kohen L, Weiss L, Wizla N, Vrielynck S, LLerena K, Le Bourgeois M, Deneuville E, Remus N, Nguyen-Khoa T, Raynal C, Roussey M, Girodon E.
Arch Pediatr. 2017 Apr;24(4):401-414. doi: 10.1016/j.arcped.2017.01.019. Epub 2017 Mar 1. French. PMID:28258861

Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.
Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR.
J Pediatr. 2017 Feb;181S:S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064. Erratum in: J Pediatr. 2017 May;184:243. PMID:28129811

Diagnosis of Cystic Fibrosis in Screened Populations.
Farrell PM, White TB, Howenstine MS, Munck A, Parad RB, Rosenfeld M, Sommerburg O, Accurso FJ, Davies JC, Rock MJ, Sanders DB, Wilschanski M, Sermet-Gaudelus I, Blau H, Gartner S, McColley SA.
J Pediatr. 2017 Feb;181S:S33-S44.e2. doi: 10.1016/j.jpeds.2016.09.065. PMID:28129810

2016

[New therapeutic developments in cystic fibrosis].
Bui S, Macey J, Fayon M; « nouvelles thérapeutiques de la Société Française pour la Mucoviscidose », Bihouée T, Burgel PR, Colomb V, Corvol H, Durieu I, Hubert D, Marguet C, Mas E, Munck A, Murris-Espin M, Reix P, Sermet-Gaudelus I.
Arch Pediatr. 2016 Dec;23(12S):12S47-12S53. doi: 10.1016/S0929-693X(17)30062-3. Review. French. PMID:28231894

Cystic fibrosis : steady progress
Paris Match |  11.13.2018
Considerable progress, commented on by Pr Isabelle Sermet-Gaudelus, has been made in its treatment.
> Read more

Cystic fibrosis : How the multidisciplinary team at Necker ensures a peaceful return to school for Pierre and his mother
20minutes.fr | 9.25.2018
On the occasion of the 34th Virades de l’espoir, « 20 Minutes » was able to visit the center dedicated to this rare disease and meet the various professionals who surround Claire and her family …
> Read more

Cystic fibrosis : promising new treatments?
Handicap.fr | 9.23.2016
Among the projects supported, that of Pr Isabelle Sermet-Gaudelus and her team at Inserm (National Institute for Health and Medical Research) aims to better target treatments. Promising treatments are arriving on the market, such as Orkambi, from the French laboratory Vertex, but « patients respond to them very differently », underlines the researcher, also a pediatrician at the Necker hospital (Paris). Testing the treatment on cells in the nasal mucosa of patients makes it possible to “predict their clinical response” and “not to treat those who will not benefit from it”, added the researcher.
> Read more

Contact information

Necker-Enfants malades university hospital
> Pediatric pneumology and allergology department
Cystic fibrosis functional unit

149 rue de Sèvres
75743 PARIS Cedex 15

> Pediatric welcome booklet

In Necker, the reference center for cystic fibrosis in brief …

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patients followed at least once a year*
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medical consultations*
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day hospitalizations*
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fully hospitalized patients*
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authorized therapeutic education program*
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patients trained in therapeutic education*
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current research projects*
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university courses*
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publications*

* data valid for 2020