1. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening
- Author
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Aleksander Edelman, Philippe Reix, Stéphanie Bui, E. Deneuville, F. Huet, Gérard Lenoir, Delphine Roussel, Gabriel Bellon, Isabelle Sermet-Gaudelus, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Régulation des systèmes de transport dans les épithéliums (UMR_S467), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Ressources et de Compétences en Mucoviscidose [CHU Toulouse] (CRCM Toulouse), Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Ressources et de Compétences de la Mucoviscidose, hôpital Sud, Hôpital d'Enfants du Bocage, Centre de Ressources et de compétences de la mucoviscidose (CRCM), Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Supported by Assistance Publique des Hôpitaux de Paris, Vaincre La Mucoviscidose and ABCF Protéines Associations., Edelman, Aleksander, Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, and Hospices Civils de Lyon (HCL) - Hospices Civils de Lyon (HCL)
- Subjects
Male ,Pathology ,Cystic Fibrosis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Mucous membrane of nose ,MESH : Equipment Design ,MESH : Child, Preschool ,MESH: Catheterization ,medicine.disease_cause ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Cystic fibrosis ,Gastroenterology ,MESH: Amiloride ,Amiloride ,Study Protocol ,MESH : Catheterization ,MESH: Genetic Screening ,Subcutaneous Tissue ,0302 clinical medicine ,MESH : Electric Conductivity ,Reference Values ,MESH : Chlorides ,MESH : Female ,030212 general & internal medicine ,Sympathomimetics ,Sweat ,MESH: Cystic Fibrosis Transmembrane Conductance Regulator ,Mutation ,biology ,medicine.diagnostic_test ,lcsh:RJ1-570 ,MESH : Infant ,Equipment Design ,MESH: Infant ,Cystic fibrosis transmembrane conductance regulator ,Electrodes, Implanted ,3. Good health ,Perfusion ,Research Design ,Child, Preschool ,Chloride channel ,Female ,France ,Sodium Channel Blockers ,MESH: Infant, Newbo ,medicine.medical_specialty ,MESH : Electrodes, Implanted ,MESH: Cystic Fibrosis ,MESH: Electric Conductivity ,Sensitivity and Specificity ,Catheterization ,03 medical and health sciences ,MESH : Amiloride ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Neonatal Screening ,Chlorides ,Predictive Value of Tests ,MESH : Cystic Fibrosis ,030225 pediatrics ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,medicine ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Immunoreactive trypsinogen ,Pediatrics, Perinatology, and Child Health ,Genetic Testing ,MESH: Chlorides ,MESH : France ,Genetic testing ,MESH : Genetic Screening ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Newborn screening ,MESH: Humans ,Ion Transport ,business.industry ,MESH : Cystic Fibrosis Transmembrane Conductance Regulator ,MESH : Humans ,MESH: Child, Preschool ,Sodium ,Electric Conductivity ,Infant, Newborn ,Isoproterenol ,Infant ,lcsh:Pediatrics ,medicine.disease ,MESH: France ,Nasal Mucosa ,MESH : Infant, Newbo ,Pediatrics, Perinatology and Child Health ,biology.protein ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,MESH: Electrodes, Implanted ,business ,MESH: Female ,MESH: Equipment Design - Abstract
Background Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. Methods/Design We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na+) transport in response to the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl-) secretion in response to isoproterenol, a β-agonist in a Cl- free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. Discussion A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.
- Published
- 2006