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1. Clues for improvement of research in objective structured clinical examination

Author: Jean Philippe Foy, Laure Serresse, Maxens Decavèle, Manon Allaire, Nadia Nathan, Marie Christine Renaud, Nada Sabourdin, Yasmine Souala-Chalet, Yanis Tamzali, Jessica Taytard, Mélanie Tran, Fleur Cohen, Hugo Bottemanne, and Antoine Monsel
Subjects: OSCE, objective structured clinical examination, scientometry, bibliometry, scientific network, Special aspects of education, LC8-6691, Medicine (General), R5-920
Abstract: While objective clinical structured examination (OSCE) is a worldwide recognized and effective method to assess clinical skills of undergraduate medical students, the latest Ottawa conference on the assessment of competences raised vigorous debates regarding the future and innovations of OSCE. This study aimed to provide a comprehensive view of the global research activity on OSCE over the past decades and to identify clues for its improvement. We performed a bibliometric and scientometric analysis of OSCE papers published until March 2024. We included a description of the overall scientific productivity, as well as an unsupervised analysis of the main topics and the international scientific collaborations. A total of 3,224 items were identified from the Scopus database. There was a sudden spike in publications, especially related to virtual/remote OSCE, from 2020 to 2024. We identified leading journals and countries in terms of number of publications and citations. A co-occurrence term network identified three main clusters corresponding to different topics of research in OSCE. Two connected clusters related to OSCE performance and reliability, and a third cluster on student’s experience, mental health (anxiety), and perception with few connections to the two previous clusters. Finally, the United States, the United Kingdom, and Canada were identified as leading countries in terms of scientific publications and collaborations in an international scientific network involving other European countries (the Netherlands, Belgium, Italy) as well as Saudi Arabia and Australia, and revealed the lack of important collaboration with Asian countries. Various avenues for improving OSCE research have been identified: i) developing remote OSCE with comparative studies between live and remote OSCE and issuing international recommendations for sharing remote OSCE between universities and countries; ii) fostering international collaborative studies with the support of key collaborating countries; iii) investigating the relationships between student performance and anxiety.
Published: 2024
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2. A roadmap to precision treatments for familial pulmonary fibrosis

Author: Killian Hurley, Mari Ozaki, Quentin Philippot, Liam Galvin, David Crosby, Mary Kirwan, Deborah R. Gill, Konstantinos-Dionysios Alysandratos, Gisli Jenkins, Matthias Griese, Nadia Nathan, Raphael Borie, Deborah Snijders, Nicolaus Schwerk, Nico Lachmann, and Daniel O'Toole
Subjects: Familial pulmonary fibrosis, Interstitial lung disease of genetic cause, precision medicine, Pulmonary fibrosis, Preclinical models, Telomere related gene, Surfactant related gene, Medicine, Medicine (General), R5-920
Abstract: Summary: Interstitial lung diseases (ILDs) in adults and children (chILD) are a heterogeneous group of lung disorders leading to inflammation, abnormal tissue repair and scarring of the lung parenchyma often resulting in respiratory failure and death. Inherited factors directly cause, or contribute significantly to the risk of developing ILD, so called familial pulmonary fibrosis (FPF), and monogenic forms may have a poor prognosis and respond poorly to current treatments. Specific, variant-targeted or precision treatments are lacking. Clinical trials of repurposed drugs, anti-fibrotic medications and specific treatments are emerging but for many patients no interventions exist. We convened an expert working group to develop an overarching framework to address the existing research gaps in basic, translational, and clinical research and identified areas for future development of preclinical models, candidate medications and innovative clinical trials. In this Position Paper, we summarise working group discussions, recommendations, and unresolved questions concerning precision treatments for FPF.
Published: 2024
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3. An evaluation of an open access iPSC training course: 'How to model interstitial lung disease using patient-derived iPSCs'

Author: Anja Schweikert, Sarah Kenny, Irene Oglesby, Arlene Glasgow, Chiara de Santi, Ingrid Gensch, Nico Lachmann, Tifenn Desroziers, Camille Fletcher, Deborah Snijders, Nadia Nathan, Killian Hurley, and COST Open-ILD Group Management Committee
Subjects: iPSCs, Interstitial lung disease, Disease modelling, European Cooperation in Science and Technology, Training course, COST Action IG16125, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract: Abstract Background Interstitial lung diseases (ILD) are a group of rare lung diseases with severe outcomes. The COST Innovator Grant aims to establish a first-of-a-kind open-access Biorepository of patient-derived induced pluripotent stem cells (iPSC) and to train researchers in the skills required to generate a robust preclinical model of ILD using these cells. This study aims to describe and evaluate the effectiveness of a training course designed to train researchers in iPSC techniques to model ILD. Methods 74 researchers, physicians and stakeholders attended the training course in Dublin in May 2022 with 31 trainees receiving teaching in practical iPSC culturing skills. The training course learners were divided into the Hands-on (16 trainees) and Observer groups (15 trainees), with the Observers attending a supervised live-streamed experience of the laboratories skills directly delivered to the Hands-on group. All participants were asked to participate in an evaluation to analyse their satisfaction and knowledge gained during the Training Course, with means compared using t-tests. Results The gender balance in both groups was predominantly females (77.4%). The Hands-on group consisted mainly of researchers (75%), whereas all participants of the Observer group described themselves as clinicians. All participants in the Hands-on group were at least very satisfied with the training course compared to 70% of the participants in the Observer group. The knowledge assessment showed that the Hands-on group retained significantly more knowledge of iPSC characteristics and culturing techniques compared to the Observers (*
Published: 2023
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4. Objectives for algorithmic decision-making systems in childhood asthma: Perspectives of children, parents, and physicians

Author: Omar Masrour, Johan Personnic, Flore Amat, Rola Abou Taam, Blandine Prevost, Guillaume Lezmi, Apolline Gonsard, Nadia Nathan, Alexandra Pirojoc, Christophe Delacourt, Stéphanie Wanin, and David Drummond
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Objectives To identify with children, parents and physicians the objectives to be used as parameters for algorithmic decision-making systems (ADMSs) adapting treatments in childhood asthma. Methods We first conducted a qualitative study based on semi-structured interviews to explore the objectives that children aged 8–17 years, their parents, and their physicians seek to achieve when taking/giving/prescribing a treatment for asthma. Following the grounded theory approach, each interview was independently coded by two researchers; reconciled codes were used to assess code frequency, categories were defined, and the main objectives identified. We then conducted a quantitative study based on questionnaires using these objectives to determine how children/parents/physicians ranked these objectives and whether their responses were aligned. Results We interviewed 71 participants (31 children, 30 parents and 10 physicians) in the qualitative study and identified seven objectives associated with treatment uptake and five objectives associated with treatment modalities. We included 291 participants (137 children, 137 parents, and 17 physicians) in the quantitative study. We found little correlation between child, parent, and physician scores for each of the objectives. Each child's asthma history influenced the choice of scores assigned to each objective by the child, parents, and physician. Conclusion The identified objectives are quantifiable and relevant to the management of asthma in the short and long term. They can therefore be incorporated as parameters for future ADMS. Shared decision-making seems essential to achieve consensus among children, parents, and physicians when choosing the weight to assign to each of these objectives.
Published: 2024
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5. CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the 'long and winding road' into adulthood

Author: Spyros A. Papiris, Camille Louvrier, Aurélie Fabre, Loukas Kaklamanis, Iraklis Tsangaris, Frantzeska Frantzeskaki, Ilias E. Dimeas, Marie-Pierre Debray, Foteini Karakontaki, Maria Kallieri, Lykourgos Kolilekas, Zoe Daniil, Alexandra Giatromanolaki, Caroline Kannengiesser, Raphael Borie, Nadia Nathan, Matthias Griese, and Effrosyni D. Manali
Subjects: Medicine
Published: 2023
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6. Outcome of lung transplantation for adults with interstitial lung disease associated with genetic disorders of the surfactant system

Author: Julien Bermudez, Nadia Nathan, Benjamin Coiffard, Antoine Roux, Sandrine Hirschi, Tristan Degot, Vincent Bunel, Jérôme Le Pavec, Julie Macey, Aurélie Le Borgne, Marie Legendre, Vincent Cottin, Pascal-Alexandre Thomas, Raphaël Borie, and Martine Reynaud-Gaubert
Subjects: Medicine
Abstract: Background Interstitial lung disease associated with genetic disorders of the surfactant system is a rare entity in adults that can lead to lung transplantation. Our objective was to describe the outcome of these patients after lung transplantation. Methods We conducted a retrospective, multicentre study, on adults who underwent lung transplantation for such disease in the French lung transplant centres network, from 1997 to 2018. Results 20 patients carrying mutations in SFTPA1 (n=5), SFTPA2 (n=7) or SFTPC (n=8) were included. Median interquartile range (IQR) age at diagnosis was 45 (40–48) years, and median (IQR) age at lung transplantation was 51 (45–54) years. Median overall survival after transplantation was 8.6 years. Two patients had a pre-transplant history of lung cancer, and two developed post-transplant lung cancer. Female gender and a body mass index
Published: 2023
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7. Diffuse alveolar haemorrhage in children: an international multicentre study

Author: Astrid Madsen Ring, Nicolaus Schwerk, Nural Kiper, Ayse Tana Aslan, Paul Aurora, Roser Ayats, Ines Azevedo, Teresa Bandeira, Julia Carlens, Silvia Castillo-Corullon, Nazan Cobanoglu, Basil Elnazir, Nagehan Emiralioğlu, Tugba Sismanlar Eyuboglu, Michael Fayon, Tugba Ramaslı Gursoy, Claire Hogg, Karsten Kötz, Bülent Karadag, Vendula Látalová, Katarzyna Krenke, Joanna Lange, Effrosyni D. Manali, Borja Osona, Spyros Papiris, Marijke Proesmann, Philippe Reix, Lea Roditis, Sune Rubak, Nisreen Rumman, Deborah Snijders, Florian Stehling, Laurence Weiss, Ebru Yalcın, Fazilcan Zirek, Andrew Bush, Annick Clement, Matthias Griese, Frederik Fouirnaies Buchvald, Nadia Nathan, and Kim Gjerum Nielsen
Subjects: Medicine
Abstract: Background Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome. Methods A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years. Results Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0–12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function. Conclusions Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.
Published: 2023
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8. SARS-CoV-2 B.1.1.529 (Omicron) Variant Causes an Unprecedented Surge in Children Hospitalizations and Distinct Clinical Presentation Compared to the SARS-CoV-2 B.1.617.2 (Delta) Variant

Author: Jessica Taytard, Blandine Prevost, Aurélie Schnuriger, Guillaume Aubertin, Laura Berdah, Lauren Bitton, Audrey Dupond-Athenor, Guillaume Thouvenin, Nadia Nathan, and Harriet Corvol
Subjects: COVID-19, children, SARS-CoV-2, delta variant, omicron variant, hospitalization, Pediatrics, RJ1-570
Abstract: BackgroundIn the midst of successive waves of SARS-CoV-2 variants, the B.1.1.529 (omicron) variant has recently caused a surge in pediatric infections and hospitalizations. This study aimed to describe and compare the symptoms, explorations, treatment and evolution of COVID-19 in hospitalized children during the successive B.1.617.2 (delta) and B.1.1.529 (omicron) waves.MethodsThis observational study was performed in the Pediatric Pulmonology Department of a University Hospital in Paris, France. All hospitalized children aged between 0 and 18 years who tested positive for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs from July 15th to December 15th 2021 (delta wave), and from December 15th 2021 to February 28th 2022 (omicron wave) were included.ResultsIn total, 53 children were included, 14 (26.4%) during the delta wave and 39 (73.6%) during the omicron wave (almost three times as many hospitalizations in half the time during the latter wave). During the omicron wave, hospitalized patients were mostly aged < 5 years (90 vs. 71% of all the children during omicron and delta waves, respectively), and tended to have fewer underlying conditions (56 vs. 79% during omicron and delta waves, respectively, p = 0.20). The omicron variant was also responsible for a different clinical presentation when compared to the delta variant, with significantly higher and often poorly tolerated temperatures (p = 0.03) and increased digestive symptoms (p = 0.01). None of the three patients who were older than 12 years were fully vaccinated.ConclusionThe dramatic increase in the hospitalization of children with COVID-19 and the modification of the clinical presentation between the latest delta and omicron waves require pediatricians to remain vigilant. It should also encourage caregivers to ensure vaccination in children older than 5 years, for whom the BNT162b2 COVID-19 vaccine has been deemed safe, immunogenic, and effective.
Published: 2022
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9. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis

Author: Raphael Borie, Caroline Kannengiesser, Laurent Gouya, Clairelyne Dupin, Serge Amselem, Ibrahima Ba, Vincent Bunel, Philippe Bonniaud, Diane Bouvry, Aurélie Cazes, Annick Clement, Marie Pierre Debray, Philippe Dieude, Ralph Epaud, Pascale Fanen, Elodie Lainey, Marie Legendre, Aurélie Plessier, Flore Sicre de Fontbrune, Lidwine Wemeau-Stervinou, Vincent Cottin, Nadia Nathan, and Bruno Crestani
Subjects: Interstitial pulmonary fibrosis, Telomerase, Surfactant, TERT, Familial, multidisciplinary discussion, Medicine
Abstract: Abstract Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.
Published: 2019
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10. Benefits and risks of bronchoalveolar lavage in severe asthma in children

Author: Raja Ben Tkhayat, Jessica Taytard, Harriet Corvol, Laura Berdah, Blandine Prévost, Jocelyne Just, and Nadia Nathan
Subjects: Medicine
Abstract: Background Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. Material and methods The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. Results In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p
Published: 2021
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11. Genetics in Idiopathic Pulmonary Fibrosis: A Clinical Perspective

Author: Spyros A. Papiris, Caroline Kannengiesser, Raphael Borie, Lykourgos Kolilekas, Maria Kallieri, Vasiliki Apollonatou, Ibrahima Ba, Nadia Nathan, Andrew Bush, Matthias Griese, Philippe Dieude, Bruno Crestani, and Effrosyni D. Manali
Subjects: interstitial lung disease, idiopathic pulmonary fibrosis, alveolar epithelial cell, short telomere syndrome, surfactant-related gene mutations, telomere-related-gene mutations, Medicine (General), R5-920
Abstract: Background: Unraveling the genetic background in a significant proportion of patients with both sporadic and familial IPF provided new insights into the pathogenic pathways of pulmonary fibrosis. Aim: The aim of the present study is to overview the clinical significance of genetics in IPF. Perspective: It is fascinating to realize the so-far underestimated but dynamically increasing impact that genetics has on aspects related to the pathophysiology, accurate and early diagnosis, and treatment and prevention of this devastating disease. Genetics in IPF have contributed as no other in unchaining the disease from the dogma of a “a sporadic entity of the elderly, limited to the lungs” and allowed all scientists, but mostly clinicians, all over the world to consider its many aspects and “faces” in all age groups, including its co-existence with several extra pulmonary conditions from cutaneous albinism to bone-marrow and liver failure. Conclusion: By providing additional evidence for unsuspected characteristics such as immunodeficiency, impaired mucus, and surfactant and telomere maintenance that very often co-exist through the interaction of common and rare genetic variants in the same patient, genetics have created a generous and pluralistic yet unifying platform that could lead to the understanding of the injurious and pro-fibrotic effects of many seemingly unrelated extrinsic and intrinsic offending factors. The same platform constantly instructs us about our limitations as well as about the heritability, the knowledge and the wisdom that is still missing.
Published: 2022
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12. Pulmonary hemosiderosis in children with Down syndrome: a national experience

Author: Aurelia Alimi, Jessica Taytard, Rola Abou Taam, Véronique Houdouin, Aude Forgeron, Marc Lubrano Lavadera, Pierrick Cros, Isabelle Gibertini, Jocelyne Derelle, Antoine Deschildre, Caroline Thumerelle, Ralph Epaud, Philippe Reix, Michael Fayon, Sylvie Roullaud, Françoise Troussier, Marie-Catherine Renoux, Jacques de Blic, Sophie Leyronnas, Guillaume Thouvenin, Caroline Perisson, Aimé Ravel, Annick Clement, Harriet Corvol, Nadia Nathan, and for the French RespiRare® group
Subjects: Pulmonary hemosiderosis, Down syndrome, Children, Autoimmunity, Interstitial lung disease, Celiac disease, Medicine
Abstract: Abstract Background Pulmonary hemosiderosis is a rare and complex disease in children. A previous study from the French RespiRare® network led to two important findings: 20% of the children presented with both pulmonary hemosiderosis and Down syndrome (DS), and at least one tested autoantibody was found positive in 50%. This study investigates the relationships between pulmonary hemosiderosis and DS. Methods Patients younger than 20 years old and followed for pulmonary hemosiderosis were retrieved from the RespiRare® database. Clinical, biological, functional, and radiological findings were collected, and DS and non-DS patients’ data were compared. Results A total of 34 patients (22 girls and 12 boys) were included, among whom nine (26%) presented with DS. The mean age at diagnosis was 4.1 ± 3.27 years old for non-DS and 2.9 ± 3.45 years old for DS patients. DS patients tended to present a more severe form of the disease with an earlier onset, more dyspnoea at diagnosis, more frequent secondary pulmonary hypertension, and an increased risk of fatal evolution. Conclusions DS patients have a higher risk of developing pulmonary hemosiderosis, and the disease seems to be more severe in this population. This could be due to the combination of an abnormal lung capillary bed with fragile vessels, a higher susceptibility to autoimmune lesions, and a higher risk of evolution toward pulmonary hypertension. A better screening for pulmonary hemosiderosis and a better prevention of hypoxia in DS paediatric patients may prevent a severe evolution of the disease.
Published: 2018
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13. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Author: Alain Calender, Pierre Antoine Rollat Farnier, Adrien Buisson, Stéphane Pinson, Abderrazzaq Bentaher, Serge Lebecque, Harriet Corvol, Rola Abou Taam, Véronique Houdouin, Claire Bardel, Pascal Roy, Gilles Devouassoux, Vincent Cottin, Pascal Seve, Jean-François Bernaudin, Clarice X. Lim, Thomas Weichhart, Dominique Valeyre, Yves Pacheco, Annick Clement, Nadia Nathan, and in the frame of GSF (Groupe Sarcoïdose France)
Subjects: Sarcoidosis, Whole-exome sequencing (WES), Candidate genes, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Sarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To find out relevant sarcoidosis predisposing genes, we searched for de novo and recessive mutations in 3 young probands with sarcoidosis and their healthy parents using a whole-exome sequencing (WES) methodology. Methods From the SARCFAM project based on a national network collecting familial cases of sarcoidosis, we selected three families (trios) in which a child, despite healthy parents, develop the disease before age 15 yr. Each trio was genotyped by WES (Illumina HiSEQ 2500) and we selected the gene variants segregating as 1) new mutations only occurring in affected children and 2) as recessive traits transmitted from each parents. The identified coding variants were compared between the three families. Allelic frequencies and in silico functional results were analyzed using ExAC, SIFT and Polyphenv2 databases. The clinical and genetic studies were registered by the ClinicalTrials.gov - Protocol Registration and Results System (PRS) (https://clinicaltrials.gov) receipt under the reference NCT02829853 and has been approved by the ethical committee (CPP LYON SUD EST – 2 – REF IRB 00009118 – September 21, 2016). Results We identified 37 genes sharing coding variants occurring either as recessive mutations in at least 2 trios or de novo mutations in one of the three affected children. The genes were classified according to their potential roles in immunity related pathways: 9 to autophagy and intracellular trafficking, 6 to G-proteins regulation, 4 to T-cell activation, 4 to cell cycle and immune synapse, 2 to innate immunity. Ten of the 37 genes were studied in a bibliographic way to evaluate the functional link with sarcoidosis. Conclusions Whole exome analysis of case-parent trios is useful for the identification of genes predisposing to complex genetic diseases as sarcoidosis. Our data identified 37 genes that could be putatively linked to a pediatric form of sarcoidosis in three trios. Our in-depth focus on 10 of these 37 genes may suggest that the formation of the characteristic lesion in sarcoidosis, granuloma, results from combined deficits in autophagy and intracellular trafficking (ex: Sec16A, AP5B1 and RREB1), G-proteins regulation (ex: OBSCN, CTTND2 and DNAH11), T-cell activation (ex: IDO2, IGSF3), mitosis and/or immune synapse (ex: SPICE1 and KNL1). The significance of these findings needs to be confirmed by functional tests on selected gene variants.
Published: 2018
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14. Bi-allelic missense ABCA3 mutations in a patient with childhood ILD who reached adulthood

Author: Effrosyni D. Manali, Marie Legendre, Nadia Nathan, Caroline Kannengiesser, Aurore Coulomb-L'Hermine, Theofanis Tsiligiannis, Pericles Tomos, Matthias Griese, Raphael Borie, Annick Clement, Serge Amselem, Bruno Crestani, and Spyros A. Papiris
Subjects: Medicine
Published: 2019
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15. Management of suspected monogenic lung fibrosis in a specialised centre

Author: Raphael Borie, Caroline Kannengiesser, Flore Sicre de Fontbrune, Laurent Gouya, Nadia Nathan, and Bruno Crestani
Subjects: Diseases of the respiratory system, RC705-779
Abstract: At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis. Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed. The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.
Published: 2017
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16. COVID‐19 and pediatric pulmonology: Feedback from an expert center after the first year of the pandemic

Author: Harriet Corvol, Blandine Prevost, Guillaume Aubertin, Guillaume Thouvenin, Jessica Taytard, and Nadia Nathan
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, Perinatology and Child Health
Abstract: The coronavirus disease 2019 (COVID-19) outbreak has evolved with different waves corresponding to subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. While the most severe cases have been observed in the elderly and in individuals with underlying comorbidities, severe pediatric and young adult cases have been observed, as well as post-infectious inflammatory syndromes and persistent symptoms leading to long-COVID. This manuscript describes the experience of a pediatric respiratory unit during the first year of the pandemic and reviews the corresponding literature with a special emphasis on children and young people with underlying conditions, such as immunosuppression, sickle cell disease, and cystic fibrosis.
Published: 2022

17. Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

Author: Pierre-Régis Burgel, Isabelle Durieu, Raphaël Chiron, Sophie Ramel, Isabelle Danner-Boucher, Anne Prevotat, Dominique Grenet, Christophe Marguet, Martine Reynaud-Gaubert, Julie Macey, Laurent Mely, Annlyse Fanton, Sébastien Quetant, Lydie Lemonnier, Jean-Louis Paillasseur, Jennifer Da Silva, Clémence Martin, Claire Andrejak, Arnaud Becourt, Julie Mounard, Claire Poulet, Cinthia Rames, Marie Talleux, Marie-Chantal Chevalier, Estelle Darviot, Marie Jouvenot, Caroline Marien, Audrey Paris, Cécile Pelatan, Christine Person, Pascaline Priou, Françoise Troussier, Thierry Urban, Marie-Laure Dalphin, Jean-Charles Dalphin, Alice Ladaurade, Didier Pernet, Bénédicte Richaud-Thiriez, Pauline Roux-Claude, Nathalia Blanc, Vincent Boisserie-Lacroix, Stephanie Bui, Cyrielle Collet, Stéphane Debelleix, Emmanuel Bergot, Jacques Brouard, Karine Campbell, Muriel Laurans, Virginie Ribault, Corinne Borderon, Marie-Christine Heraud, Guillaume Labbe, Sylvie Montcouquiol, Isabelle Petit, Marc Ruivard, Céline Delestrain, Benoit Douvry, Ralph Epaud, Bernard Maitre, Natascha Remus, Guillaume Beltramo, Anne Houzel, Frédéric Huet, Stéphanie Perez, Amale Boldron-Ghaddar, Manuela Scalbert, Rabah Bouzioukh, Charles Simon, Boubou Camara, Rébecca Hamidfar, Catherine Llerena, Isabelle Pin, Antoine Deschildre, Alice Gicquello, Olivier Le Rouzic, Clara Leroy, Nicolas Paris, Thierry Perez, Caroline Thumerelle, Dominique Turck, Nathalie Wizla, Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, Céline Menetrey, Stéphane Durupt, Sophie L’Excellent, Raphaele Nove-Josserand, Camille Ohlmann, Phillipe Reix, Quitterie Reynaud, Marie-Christine Werck-Gallois, Mélissandre Baravalle, Bérangère Coltey, Nadine Desmazes-Dufeu, Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Nathalie Stremler, Davide Caimmi, Margot Devrait, Johan Moreau, Yves Billon, Aurore Blondé, Anne Guillaumot, Sébastien Kiefer, Laura Peretti, Aurélie Tatopoulos, Angélica Tiotiu, Myriam Benhamida, Tiphaine Bihouee, Emmanuel Eschapasse, Adrien Tissot, Marie Giannantonio, Sylvie Leroy, Carole Piccini-Bailly, Johana Pradelli, Jonathan Messika, Véronique Boussaud, Nicolas Carlier, Isabelle Honoré, Dominique Hubert, Reem Kanaan, Céline Bailly-Botuha, Frédérique Chedevergne, Jacques De Blic, Christophe Delacourt, David Drummond, Brigitte Fauroux, Chantal Karila, Muriel Le Bourgeois, Isabelle Sermet, Bertrand Delaisi, Michèle Gerardin, Veronique Houdouin, Laurence Leclainche, Guillaume Aubertin, Laura Berdah, Annick Clement, Harriet Corvol, Nadia Nathan, Blandine Prevost, Nicolas Richard, Aline Tamalet, Jessica Taytard, Guillaume Thouvenin, Barbara Tourniaire, Michel Abely, Katia Bessaci-Kabouya, Sandra Dury, Bruno Ravoninjatovo, Alain Dabadie, Michel Dagorne, Eric Deneuville, Marie Jamin, Mélanie Ribault, Clémentine Vigier, Chantal Belleguic, Graziella Brinchault, Benoit Desrues, Audrey Barzic, Anne Dirou-Prigent, Jean Le Bihan, Krista Revert, Thomas Ropars, Laure Couderc, Stéphane Dominique, Hélène Morisse-Pradier, Stéphanie Pramil, Luc Thiberville, Nathalie Allou, Laurent Enaud, Elsa Gachelin, Eric Huchot, Annabelle Payet, Caroline Perisson, Saguiraly Piyaraly, Sophie Valois, Audrey Herzog, Romain Kessler, Michele Porzio, Laurence Weiss, Laurence Beaumont, Olivier Brugiere, Sylvie Colin, de Verdiere, Elise Cuquemelle, Sandra De Miranda, Adbdul Monem Hamid, François Parquin, Clément Picard, Antoine Roux, Charlotte Roy, François Bremont, Alain Didier, Marion Dupuis, Guillaume Faviez, Géraldine Labouret, Marie Mittaine, Marlène Murris-Espin, Léa Roditis, Laure Cosson, Patrice Diot, Thomas Flament, Charlotte Giraut, Julie Mankikian, Baptiste Arnouat, Gaétane Mousset, Véronique Storni, Philippe Vigneron, Emmanuelle Coirier-Duet, Asma Gabsi, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Université de Lyon, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation ILDYS (ILDYS), Institut du Thorax [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], CHU Rouen, Normandie Université (NU), INSERM-TRANSFERT [Paris] (IT), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), CHU Bordeaux [Bordeaux], Hôpital Renée Sabran [CHU - HCL], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, EFFI-STAT, URC/CIC Paris Descartes Necker Cochin, Hôpital Necker, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Supported by Vaincre la Mucoviscidose, Fondation Sauver la Vie, Universite Paris Descartes, Filiere Maladies Rares Muco-CFTR, and Legs PascalBonnet., Participating Investigators of the FrenchCystic Fibrosis Reference Network StudyGroup:Claire Andrejak, Arnaud Becourt, JulieMounard, Claire Poulet, Cinthia Rames, MarieTalleux (Amiens), Marie-Chantal Chevalier,Estelle Darviot, Marie Jouvenot, Caroline Marien,Audrey Paris, C ecile Pelatan, Christine Person,Pascaline Priou, Franc ̧oise Troussier, ThierryUrban (Angers-Le Mans), Marie-Laure Dalphin,Jean-Charles Dalphin, Alice Ladaurade, DidierPernet, B en edicte Richaud-Thiriez, PaulineRoux-Claude (Besanc ̧on), Nathalia Blanc,Vincent Boisserie-Lacroix, Stephanie Bui,Cyrielle Collet, St ephane Debelleix, Julie Macey(Bordeaux), Emmanuel Bergot, JacquesBrouard, Karine Campbell, Muriel Laurans,Virginie Ribault (Caen), Corinne Borderon,Marie-Christine Heraud, Guillaume Labbe,SylvieMontcouquiol, Isabelle Petit, Marc Ruivard(Clermont-Ferrand), C eline Delestrain, BenoitDouvry, Ralph Epaud, Bernard Maitre, NataschaRemus (Cr eteil), Guillaume Beltramo, AnnlyseFanton, Anne Houzel, Fr ed eric Huet, St ephaniePerez (Dijon), AmaleBoldron-Ghaddar, ManuelaScalbert (Dunkerque), Rabah Bouzioukh,Laurent Mely, Charles Simon (Giens), BoubouCamara, R ebecca Hamidfar, Catherine Llerena,Isabelle Pin, S ebastien Quetant (Grenoble), Antoine Deschildre, Alice Gicquello, Olivier LeRouzic, Clara Leroy, Nicolas Paris, Thierry Perez,Anne Prevotat, Caroline Thumerelle, DominiqueTurck, Nathalie Wizla (Lille), Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, C eline Menetrey (Limoges), IsabelleDurieu, St ephane Durupt, Sophie L’Excellent,Raphaele Nove-Josserand, Camille Ohlmann,Phillipe Reix, Quitterie Reynaud, Marie-ChristineWerck-Gallois (Lyon), M elissandre Baravalle,B erang ere Coltey, Nadine Desmazes-Dufeu,Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Martine Reynaud-Gaubert,Nathalie Stremler (Marseille), Davide Caimmi,Rapha€el Chiron, Margot Devrait, Johan Moreau(Montpellier), Yves Billon, Aurore Blond e, AnneGuillaumot, S ebastien Kiefer, Laura Peretti,Aur elie Tatopoulos, Ang elica Tiotiu (Nancy), Myriam Benhamida, Tiphaine Bihouee, IsabelleDanner-Boucher, Emmanuel Eschapasse,Adrien Tissot (Nantes), Marie Giannantonio,Sylvie Leroy, Carole Piccini-Bailly, JohanaPradelli (Nice), Jonathan Messika (Paris, Bichat), V eronique Boussaud, Pierre-R egis Burgel,Nicolas Carlier, Isabelle Honor e, DominiqueHubert, Reem Kanaan, Cl emence Martin (Paris,Cochin), C eline Bailly-Botuha, Fr ed eriqueChedevergne, Jacques De Blic, ChristopheDelacourt, David Drummond, Brigitte Fauroux,Chantal Karila, Muriel Le Bourgeois, IsabelleSermet (Paris, Necker), Bertrand Delaisi,Mich ele Gerardin, Veronique Houdouin,Laurence Leclainche (Paris, Robert Debr e), Guillaume Aubertin, Laura Berdah, AnnickClement, Harriet Corvol, Nadia Nathan, BlandinePrevost, Nicolas Richard, Aline Tamalet, JessicaTaytard, Guillaume Thouvenin, BarbaraTourniaire (Paris, Trousseau), Michel Abely,Katia Bessaci-Kabouya, Sandra Dury, BrunoRavoninjatovo (Reims), Alain Dabadie, MichelDagorne, Eric Deneuville, Marie Jamin, M elanieRibault, Cl ementine Vigier (Rennes – SaintBrieuc), Chantal Belleguic, Graziella Brinchault,Benoit Desrues (Rennes), Audrey Barzic, AnneDirou-Prigent, Jean Le Bihan, Sophie Ramel,Krista Revert, Thomas Ropars (Roscoff), LaureCouderc, St ephane Dominique, ChristopheMarguet, H el ene Morisse-Pradier, St ephaniePramil, Luc Thiberville (Rouen), Nathalie Allou,Laurent Enaud, Elsa Gachelin, Eric Huchot,Annabelle Payet, Caroline Perisson, SaguiralyPiyaraly, Sophie Valois (La R eunion), AudreyHerzog, Romain Kessler, Michele Porzio,Laurence Weiss (Strasbourg), LaurenceBeaumont, Olivier Brugiere, Sylvie Colin deVerdiere, Elise Cuquemelle, Sandra De Miranda,Dominique Grenet, Adbdul Monem Hamid,Franc ̧ois Parquin, Cl ementPicard, Antoine Roux,Charlotte Roy (Suresnes), Franc ̧ois Bremont,Alain Didier, Marion Dupuis, Guillaume Faviez,G eraldine Labouret, Marie Mittaine, Marl eneMurris-Espin, L ea Roditis (Toulouse), LaureCosson, Patrice Diot, Thomas Flament, CharlotteGiraut, JulieMankikian(Tours), Baptiste Arnouat,Ga etane Mousset, V eronique Storni, PhilippeVigneron (Vannes-Lorient), and Emmanuelle Coirier-Duet, and Asma Gabsi (Versailles)
Subjects: Lung Diseases, Male, elexacaftor, Indoles, Cystic Fibrosis, Pyridines, medicine.medical_treatment, Regulator, Aminophenols, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Gastroenterology, Membrane Potentials, Ivacaftor, 0302 clinical medicine, Prospective Studies, 030212 general & internal medicine, Chloride Channel Agonists, Aged, 80 and over, Middle Aged, Transmembrane protein, Drug Combinations, Quinolines, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, cystic fibrosis transmembrane conductance regulator modulators, Adolescent, Pulmonary disease, Young Adult, 03 medical and health sciences, Internal medicine, lung transplantation, medicine, Humans, Lung transplantation, In patient, Aged, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Editorials, medicine.disease, 030228 respiratory system, Tezacaftor, Pyrazoles, business
Abstract: International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)
Published: 2021

18. Syndrome COPA, quoi de neuf cinq ans après ?

Author: Nadia Nathan, Marie-Louise Frémond, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Paris (UP)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Resume Des mutations heterozygotes du gene COPA, qui code la sous-unite alpha du coatomere (COPA), causent une interferonopathie monogenique principalement associee a des atteintes pulmonaire, articulaire et renale. Le syndrome COPA est une maladie auto-inflammatoire rare, caracterisee par une expression variable et une absence de penetrance frequemment observee. La quasi-totalite des patients ont des symptomes pulmonaires, des hemorragies intra-alveolaires (HIA) chroniques ou une pneumopathie interstitielle diffuse, qui peuvent aboutir a une insuffisance respiratoire de stade terminal. Le phenotype initialement decrit s’est elargi et inclut les HIA isolees ou la nephrite lupique. Des manifestations rares, rappelant d’autres interferonopathies monogeniques, peuvent etre observees. Une evaluation clinique rigoureuse est par consequent necessaire lorsqu’un syndrome COPA est suspecte ou confirme. Compte tenu de la transmission genetique dominante et de la variabilite du phenotype qui peut aller de l’absence de penetrance a des atteintes multi-organiques severes, un depistage familial rigoureux est recommande. De nouvelles donnees sur la physiopathologie de cette maladie ont relie les mutations de COPA a la voie de signalisation de l’interferon induite par STING. En depit de l’efficacite variable des immunosuppresseurs classiques, les inhibiteurs des Janus kinases (JAK) constituent un traitement prometteur dans le syndrome COPA et de nouvelles therapies ciblees sont attendues.
Published: 2021

19. French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management

Author: Candice Fabre, Caroline Thumerelle, Morgane Dervaux, Rola Abou-Taam, Tiphaine Bihouee, Jacques Brouard, Annick Clement, Christophe Delacourt, Céline Delestrain, Ralph Epaud, Sofiane Ghdifan, Alice Hadchouel, Véronique Houdouin, Géraldine Labouret, Caroline Perisson, Philippe Reix, Marie-Catherine Renoux, Françoise Troussier, Laurence Weiss, Julie Mazenq, Nadia Nathan, Jean-Christophe Dubus, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Intercommunal de Créteil (CHIC), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Sud Saint Pierre [Ile de la Réunion], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Hyperplasia, Clinical score, Neuroendocrine cell hyperplasia of infancy, Childhood interstitial lung disease, Cohort, Infant, Newborn, Infant, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Rare Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Neuroendocrine Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anti-inflammatory drugs, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pediatrics, Perinatology and Child Health, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Child, Lung Diseases, Interstitial, Children, Lung, Retrospective Studies
Abstract: Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%).This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs.•Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy.•In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.
Published: 2022

20. Paediatric sarcoidosis

Author: Nadia Nathan and Alice Hadchouel
Published: 2022

21. Childhood Interstitial Lung Diseases (chILD) Recognition: When Epidemiology Increases a Rare Disease Incidence

Author: Nadia Nathan
Subjects: Pulmonary and Respiratory Medicine
Published: 2022

22. Diffuse Parenchymal Lung Disease in Early Childhood

Author: Blandine Prevost, Chiara Sileo, and Nadia Nathan
Published: 2022

23. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis

Author: Ralph Epaud, Serge Amselem, Philippe Bonniaud, Clairelyne Dupin, Aurélie Plessier, Annick Clement, Vincent Cottin, Flore Sicre de Fontbrune, Lidwine Wemeau-Stervinou, Vincent Bunel, Diane Bouvry, Marie Pierre Debray, Caroline Kannengiesser, Aurélie Cazes, Bruno Crestani, Marie Legendre, Raphael Borie, Ibrahima Ba, Nadia Nathan, Philippe Dieudé, Elodie Lainey, Laurent Gouya, Pascale Fanen, Centre de Référence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Avicenne [AP-HP], Centre de Référence des Maladies Pulmonaires Rares [AP-HP Bobigny], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Centre des maladies respiratoires rares Respirare [CHI Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP Hôpital universitaire Robert-Debré [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Centre de compétences des maladies pulmonaires rares de l'adulte [CHU Lille] (CRMPR), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie [Hôpital Louis Pradel – CHU Lyon] (Centre de Référence des Maladies Pulmonaires Rares), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-CHU Lyon, and Couvet, Sandrine
Subjects: Male, MESH: Familial, multidisciplinary discussion, Interstitial pulmonary fibrosis, Surfactant, TERT, Telomerase, Pulmonary Fibrosis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Organ transplantation, 0302 clinical medicine, Pulmonary fibrosis, Pharmacology (medical), 030212 general & internal medicine, Child, Genetics (clinical), medicine.diagnostic_test, Interstitial lung disease, General Medicine, Middle Aged, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], Child, Preschool, Female, Familial, Adult, medicine.medical_specialty, Adolescent, Genetic counseling, MEDLINE, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Multidisciplinary team, Surface-Active Agents, Young Adult, 03 medical and health sciences, medicine, Humans, Genetic Testing, Intensive care medicine, Aged, Genetic testing, business.industry, Research, lcsh:R, Infant, medicine.disease, Human genetics, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, RNA, business
Abstract: Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.
Published: 2019

24. Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study

Author: Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Jean-Marc Naccache, Catherine Chapelon-Abric, Céline Delestrain, Julien Haroche, Ralph Epaud, Ulrich Meinzer, Simon Chauveau, Fleur Cohen-Aubart, Mickaël Catinon, Florence Jeny, Odile Macchi, Sylvain Le Jeune, Hilario Nunes, Michel Vincent, Paul-André Rosental, Manon Brocvielle, Marie-Hélène Odièvre, Marie-Emeline Montagne, S. Mattioni, Dominique Valeyre, Karine Juvin, Annick Clement, Dominique Israël-Biet, A. Dossier, Nadia Nathan, Jacques Brouard, François Lionnet, Lucile Sesé, Rola Abou Taam, Christophe Delacourt, Marie Mittaine, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Pneumologie et allergologie pédiatriques [CHU Jeanne de Flandre, Lille], Hôpital Jeanne de Flandre [Lille], Université de Lille, Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Pneumologie, soins intensifs (Pneumo - HEGP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], CHU Tenon [AP-HP], Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPC), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Sciences Po (Sciences Po), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Observatoire du Samu Social de Paris, CHU Necker - Enfants Malades [AP-HP], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre des maladies respiratoires rares Respirare [CHI Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de médecine interne [Avicenne], Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Groupe Hospitalier Paris Saint-Joseph (hpsj), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Centre d'études de l'emploi et du travail (CEET), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère du Travail, de l'Emploi et de la Santé, contract grant sponsor: European Research Council (ERC) / SILICOSISproject / Principal investigator: Paul-André Rosental, Contract grant number: ERC2011-ADG_20110406ˆProject ID: 295817. Statistical analysis: RespiFIL funds, European Project: 295449,EC:FP7:ERC,ERC-2011-ADG_20110406,DARTCH(2012), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'études européennes et de politique comparée (CEE), Centre d'histoire de Sciences Po (CHSP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)
Subjects: Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, paediatric interstitial lung disease, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occupational Exposure, medicine, Humans, sarcoidosis, Occupational lung disease, Occupations, Child, Inorganic particles, 030304 developmental biology, 0303 health sciences, Median score, rare lung diseases, business.industry, Dust, Environmental exposure, Environmental Exposure, medicine.disease, 3. Good health, 030228 respiratory system, Metal dust, Talc, Sarcoidosis, business, occupational lung disease
Abstract: International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
Published: 2021

25. Severe asthma in children: shall we carry out systematic bronchoalveolar lavage?

Author: Nadia Nathan, Raja Ben Tkhayat, and Jocelyne Just
Subjects: medicine.medical_specialty, Bronchoalveolar lavage, medicine.diagnostic_test, business.industry, Severe asthma, Internal medicine, medicine, business
Published: 2021

26. Mineral exposures in pediatric sarcoidosis

Author: Jean-Marc Naccache, François Lionnet, Lucile Sesé, Ulrich Meinzer, Fleur Cohen Aubart, Karine Juvin, Marie-Hélène Odièvre, Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Dominique Valeyre, Dominique Israel-Biet, Paul-André Rosental, Florence Jeny, Michel Vincent, Sylvain Le Jeune, Annick Clement, Jacques Brouard, Nadia Nathan, Ralph Epaud, Odile Macchi, Simon Chauveau, S. Mattioni, Mickaël Catinon, Céline Delestrain, Marie-Emeline Montagne, Julien Haroche, Hilario Nunes, Rola Abou Taam, Catherine Chapelon-Abric, Christophe Delacourt, Marie Mittaine, and A. Dossier
Subjects: medicine.medical_specialty, Mineral, business.industry, medicine, Sarcoidosis, medicine.disease, business, Dermatology
Published: 2021

27. Late Breaking Abstract - Good outcome for lung transplantation for adults with interstitial lung disease associated with genetic disorders of surfactant metabolism

Author: Raphael Borie, Julien Bermudez, Sandrine Hirschi, Vincent Cottin, Julie Macey, Antoine Roux, Aurélie Leborgne-Krams, Vincent Bunel, Benjamin Coiffard, Tristan Dégot, Martine Reynaud-Gaubert, Jérôme Le Pavec, and Nadia Nathan
Subjects: medicine.medical_specialty, Pulmonary surfactant, business.industry, medicine.medical_treatment, Internal medicine, medicine, Interstitial lung disease, Lung transplantation, Metabolism, Good outcome, business, medicine.disease, Gastroenterology
Published: 2021

28. Diffuse alveolar haemorrhage in children: an international multicentre study

Author: Sune Rubak, Marie-Catherine Renoux, Paul Aurora, Annick Clement, Katarzyna Krenke, Nural Kiper, Ebru Yalçin, Silvia Castillo-Corullón, Inês Azevedo, Borja Osona, Laurence Weiss, Léa Roditis, Philippe Reix, Andrew Bush, Caroline Thumerelle, Frederik Buchvald, Nadia Nathan, Marijke Proesmann, Nicolaus Schwerk, Ayse Tana Aslan, Basil Elnazir, Matthias Griese, Kim G. Nielsen, Nisreen Rumman, Claire Hogg, Fazilcan Zirek, Nagehan Emiralioglu, Teresa Bandeira, Astrid Madsen Ring, Tugba Sismanlar Eyuboglu, Bulent Karadag, Nazan Cobanoglu, Vendula Látalová, Roser Ayats, Julia Carlens, Joanna Lange, and Tugba Gursoy
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Medicine, business
Published: 2021

29. Severe Acute Respiratory Syndrome Coronavirus 2 Variant Delta Infects All 6 Siblings but Spares Comirnaty (BNT162b2, BioNTech/Pfizer)-Vaccinated Parents

Author: Nadia Nathan, Sidonie Lambert, Harriet Corvol, Aurélie Schnuriger, and Blandine Prevost
Subjects: Delta, Parents, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evasion, resistance, Major Articles and Brief Reports, spike mutation, Immunology and Allergy, Medicine, Humans, neutralizing antibodies, BNT162 Vaccine, business.industry, SARS-CoV-2, infectivity, Siblings, COVID-19, Indian variant, Virology, fitness, Infectious Diseases, AcademicSubjects/MED00290, Covid-2019, antibody escape, business, B.1.617
Abstract: The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that 2 key mutations seen in the receptor-binding domain, L452R and E484Q, would have additive effects on evasion of neutralizing antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine-elicited neutralizing antibodies by L452R and E484Q but lack of synergistic loss of sensitivity.
Published: 2021

30. Interstitial lung diseases in the neonatal period

Author: Marie Legendre, Aurore Coulomb L'Hermine, Chiara Sileo, Nadia Nathan, and Yohan Soreze
Subjects: Lung, medicine.anatomical_structure, business.industry, Period (gene), Physiology, Medicine, business
Published: 2021

31. Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage

Author: Yanick J. Crow, Hugues Begueret, Serge Amselem, Hubert Ducou Le Pointe, Michael Fayon, Marie-Louise Frémond, Gillian I. Rice, Nadia Nathan, Darragh Duffy, Emilie Filhol-Blin, Laura Berdah, Nicolas Richard, Vincent Bondet, Chiara Sileo, Annick Clement, Marie Legendre, Aurore Coulomb, Bénédicte Neven, Sylvie Roullaud, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier d'Angoulême (CH Angoulême), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Immunobiologie des Cellules dendritiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Edinburgh, Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des maladies génétiques d'expression pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service de Pneumologie Pédiatrique [CHU Trousseau], Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), and ANR-16-CE17-0010,IFNX,Investigation des interferonopathies type I humaine(2016)
Subjects: Lung Diseases, massive haemoptysis, Pulmonary and Respiratory Medicine, Ruxolitinib, Hemosiderosis, paediatric interstitial lung disease, Arthritis, Hemorrhage, Disease, 03 medical and health sciences, 0302 clinical medicine, Interferon, Nitriles, medicine, Humans, 030212 general & internal medicine, Child, rare lung diseases, business.industry, Interstitial lung disease, medicine.disease, 3. Good health, systemic disease and lungs, Pyrimidines, 030228 respiratory system, Pulmonary haemosiderosis, Coatomer, Mutation (genetic algorithm), Immunology, Pyrazoles, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, paediatric lung disaese, business, medicine.drug
Abstract: COPA (coatomer subunit α) syndrome is a newly recognised cause of interstitial lung disease in children and adults, frequently associated with arthritis and renal dysfunction. We report a 11-year-old girl with disease limited to major pulmonary haemosiderosis manifesting at the age of 2 years, due to a heterozygous p.(Arg233His) mutation in COPA. Her interferon (IFN) signature was elevated (10.312 and 12.429, healthy COPA screening. Functional tests can help to personalise patient therapy.
Published: 2019

32. Bi-allelic missense ABCA3 mutations in a patient with childhood ILD who reached adulthood

Author: Caroline Kannengiesser, Spyros Papiris, Serge Amselem, Raphael Borie, Annick Clement, Pericles Tomos, Bruno Crestani, Marie Legendre, Nadia Nathan, Matthias Griese, Effrosyni D. Manali, Aurore Coulomb-L'Hermine, Theofanis Tsiligiannis, Couvet, Sandrine, National and Kapodistrian University of Athens (NKUA), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mitera Pediatric Hospital [Athens], Ludwig-Maximilians University [Munich] (LMU), German Center for Lung Research, Centre de Référence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Referral, [SDV]Life Sciences [q-bio], lcsh:Medicine, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, ABCA3, 03 medical and health sciences, 0302 clinical medicine, Text mining, Medicine, Missense mutation, 030212 general & internal medicine, Allele, Adult patients, biology, business.industry, lcsh:R, Original Research Letter, respiratory system, 3. Good health, Molecular analysis, [SDV] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030228 respiratory system, biology.protein, business
Abstract: The adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3) is a transmembrane glycoprotein that uses energy of ATP hydrolysis to transport phospholipids into the lamellar bodies of type 2 alveolar epithelial cells (AEC) and regulates lung surfactant homeostasis. More than 200 mutations have already been described in ABCA3, located on chromosome 16 [1, 2]. Patients present with a great heterogeneity of phenotypes, from lethal neonatal respiratory distress syndrome (RDS) to childhood and rarely adult interstitial lung disease (ILD) [3, 4]. ABCA3 mutations-related lung disease inheritance is autosomal recessive, as it requires two disease-causing (bi-allelic) mutations, one from each parent., Children with ABCA3 mutations may survive beyond infancy and reach adulthood. Genetic mechanisms should always be examined in adult patients with childhood onset ILD and molecular analysis should be performed accordingly in specialised referral centres. http://bit.ly/2LzMNOE
Published: 2019

33. Paediatric sarcoidosis

Author: Nadia Nathan, Chiara Sileo, Alain Calender, Yves Pacheco, Paul-André Rosental, Catherine Cavalin, Odile Macchi, Dominique Valeyre, Annick Clement, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Centre d'histoire de Sciences Po (CHSP), Sciences Po (Sciences Po), Centre d'études européennes et de politique comparée (CEE), Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Service de Génétique Moléculaire et Clinique, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris Dauphine-PSL, Pneumologie Pédiatrique, AP-HP-CHU Trousseau [APHP], Physiopathologie des maladies génétiques d'expression pédiatrique, Immunovirologie et polymorphisme génétique, Université de Nantes (UN), Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, CCSD, Accord Elsevier, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Institut National de la Recherche Agronomique (INRA)-Université Paris Dauphine-PSL, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: Pulmonary and Respiratory Medicine, disease, Granuloma, Adolescent, Sarcoidosis, Infant, Interstitial lung disease, [SHS.SCIPO]Humanities and Social Sciences/Political science, [SHS]Humanities and Social Sciences, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Sarcoidosis, Pulmonary, 030228 respiratory system, Child, Preschool, Pediatrics, Perinatology and Child Health, Disease Progression, Humans, Genetic Predisposition to Disease, [SHS] Humanities and Social Sciences, 030212 general & internal medicine, Child, Lung, Children
Abstract: International audience; Paediatric sarcoidosis is an extremely rare disease characterized by a granulomatous inflammation. The estimated incidence is 0.6–1.02/100,000 children, but in the absence of international registers, the disease is probably under-reported. Its pathophysiologic basis is not clearly understood but the current hypothesis is a combination of a genetic predisposition and an environmental exposure that could be either organic or mineral. Contrary to adult forms of the disease, general symptoms are often at the forefront at diagnosis. In its most frequent form, paediatric sarcoidosis is a multi-organ disorder affecting preferentially the lungs, the lymphatic system and the liver, but all organs can be affected. This review aims to provide an overview of current knowledge on sarcoidosis in children, providing a summary of the data available from cohort studies on the presentation, the management and the evolution of the disease in this specific population.
Published: 2019

34. Benefits and risks of bronchoalveolar lavage in severe asthma in children

Author: Blandine Prevost, Nadia Nathan, Laura Berdah, Raja Ben Tkhayat, Harriet Corvol, Jocelyne Just, Jessica Taytard, Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service d'Allergologie pédiatrique [CHU Trousseau], Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], and Gestionnaire, Hal Sorbonne Université
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Severe asthma, Asthma management, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Bronchoscopy, Internal medicine, Original Research Articles, Medicine, 030212 general & internal medicine, Flexible bronchoscopy, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, medicine.diagnostic_test, business.industry, Asthma symptoms, respiratory system, University hospital, Asthma, 3. Good health, respiratory tract diseases, Bronchoalveolar lavage, 030228 respiratory system, business, Tracheobronchial malacia
Abstract: Background Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. Material and methods The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. Results In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p, Bronchoalveolar lavage can help characterise severe asthma in children. However, it can be poorly tolerated and, in most cases, its impact on the patient's management remains limited. https://bit.ly/39XOlMt
Published: 2021

35. Interstitial lung diseases

Author: Nadia Nathan, Laura Berdah, and Annick Clement
Published: 2021

36. Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer

Author: Emilie Filhol-Blin, Serge Amselem, Vincent Cottin, Diane Bouvry, J. Bermudez, Bérénice Doray, Martine Reynaud-Gaubert, Violaine Giraud, Julie Traclet, Aurélie Le Borgne, Clairelyne Dupin, Sylvie Leroy, Nathalie Allou, Paul De Vuyst, Anne Bergeron, Anne-Laure Chene, Aurore Coulomb L'Hermine, Bruno Crestani, Raphael Borie, Clément Picard, Mélanie Héry, Anne Gondouin, Bruno Copin, Tifenn Desroziers, Elisabeth Longchampt, Philippe Duquesnoy, Jean-Charles Dalphin, Valérie Nau, Annick Clement, Dominique Israël-Biet, Christine Dombret, Caroline Kannengiesser, Gwenael Lorillon, Marie Legendre, Nadia Nathan, Afifaa Butt, Aurélie Cazes, Florence Dastot-Le Moal, Hilario Nunes, Marie-Pierre Debray, Laurent Gouya, Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Ambroise Paré [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Pasteur [Nice] (CHU), Hôpital Foch [Suresnes], Hôpital Erasme [Bruxelles], Couvet, Sandrine, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), UF de Génétique moléculaire [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Mutation, Lung, business.industry, Genetic heterogeneity, medicine.medical_treatment, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease, medicine.disease_cause, Penetrance, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, SFTPA2, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunology, Medicine, Adenocarcinoma, Lung transplantation, business, Lung cancer
Abstract: IntroductionInterstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.
Published: 2020

37. Multidisciplinary team meetings dedicated to children interstitial lung diseases (chILD) – a 2-years experience

Author: Nadia Nathan, Alice Hadchouel, Maryem Sari Hassoun, Céline Lustremant, Delphine Habouria, Annick Clement, Ralph Epaud, and For The Respirare And Respifil Groups
Subjects: medicine.medical_specialty, Heterogeneous group, Treatment issues, business.industry, Family medicine, Genetic counseling, Etiology, Medicine, business, Multidisciplinary team, Pulmonologists
Abstract: Introduction: ChILD represent a heterogeneous group of rare and mostly severe disorders. In France, around 400 patients with chILD are listed. In adults, multidisciplinary teams (MDT) meetings are recognized as a crucial tool in such rare lung diseases. We aim at reporting the French experience of MDT meetings for chILD. Methods: On-line, video-conference MDT meetings have been held every month since 2018. For each patient, a standardized form is filled up by the clinician and sent to the Reference center for rare lung diseases (www.respiFIL.fr, www.respirare.fr). The MDT meetings include experts in the field with the aim of discussing diagnosis or treatment issues related to ChILD. After the MDT meeting, a report is established and sent to the requesting team. Results: In the last 20 months, 20 MDT were held and 107 patients were discussed. Participants were pediatric pulmonologists, geneticists, genetic counselor, pathologist, pediatric radiologists, and adult pulmonologists. The median age of the patients was 2 years-old. They were mainly followed in France but 14 (13%) patients were presented by international colleagues. The demands included a diagnosis issue (2%), management (19%), or both (75%). The MDT meetings allowed to precise or modify the ILD etiology in 1/3 of the patients; and to excluded ILD in 11 (10%). ILD remained of undefined cause for 19 (24%) vs 25 (32%). Conclusion: MDT meetings for chILD are easily feasible. They provide an important epidemiologic input by increasing the chILD case collection (+25%). They are an opportunity to collectively improve our knowledge on diagnosis and management of these rare diseases and to discuss genetic council issues.
Published: 2020

38. Telomere-Related Gene mutations in a Greek cohort of suspected monogenic pulmonary fibrosis patients

Author: Aikaterini Markopoulou, Athina Trachalaki, Effrosyni D. Manali, Evangelos Bouros, Spyros Papiris, Nadia Nathan, Paschalis Steiropoulos, Chrysa Bazaka, Athanasios Konstantinidis, Nikolaos Malamadakis, Anna Karakatsani, Khedidja Rebah, Caroline Kannengiesser, Raphael Borie, Lykourgos Kolilekas, Theodoros P. Vassilakopoulos, Demosthenes Bouros, Evangelos Markozannes, Zoe Daniil, Ilias Papanikolaou, Aggeliki Haritou, Ioanna Korbila, Vasilios Tzilas, Panagiotis Lyberopoulos, Sofia Spyropoulou, Andriana I. Papaioannou, Ioannis Tomos, Areti Xyfteri, Konstantinos Kagouridis, Catherine Boileau, Evangelia Fouka, Despoina Papakosta, Philippe Dieudé, Elodie Lainey, Bruno Crestani, Maria Maniati, Patrick Revy, Katerina M. Antoniou, Athina Gogali, Marie Legendre, Ibrahima Ba, Claire Oudin, Argyrios Tzouvelekis, Stylianos Loukides, and Christelle Ménard
Subjects: medicine.medical_specialty, business.industry, Interstitial lung disease, Context (language use), Disease, medicine.disease, Gastroenterology, FEV1/FVC ratio, DLCO, Internal medicine, Pulmonary fibrosis, Cohort, medicine, Genetic predisposition, business
Abstract: Background: Telomere-related genes (TRG) mutations are detected in 30% of familial pulmonary fibrosis (FPF) and are also associated with personal/familial extra-pulmonary disease suggestive of short telomere syndrome (STS). Aim: to evaluate the prevalence of TRG mutations in a national cohort of interstitial lung disease (ILD) with suspected genetic predisposition in Greece and to define patients’ characteristics and impact on outcome.Methods: Genetic diagnoses made between December 2014-September 2019 in patients with FPF, pulmonary fibrosis at young age or personal and/or family extra-pulmonary disease suggestive of STS were analyzed. Results: 150 ILD patients, 73% male, age-at-diagnosis 67 years old, 33% non-smokers, 75% with definite/probable UIP or CPFE, 93% with dyspnea/cough, FVC% pred 75%, DLCO% pred 49% were tested; FPF was 65%, 19% young age, 21% personal and 17% family extra-pulmonary disease suggestive of STS; 21% were tested for more than 1 indication. TRG pathogenic variations were detected in 19 (13%): 13 in a familial, 3 in young age and 3 in extra-pulmonary disease suggestive of STS context as follows: TERT, TERC, RTEL1, PARN, NOP10, NHP2 in 8,5,2,2,1 and 1 respectively. No difference was detected in epidemiological-clinical-radiologic-functional characteristics between patients without and with mutations apart from age-at-diagnosis [69 vs 62 years, p
Published: 2020

39. Lung ultrasound in children with interstitial lung disease: a pilot study

Author: Nadia Nathan, Laura Berdah, Fouad Madhi, Annick Clement, Houmam El Jurdi, Céline Delestrain, Harriet Corvol, Ralph Epaud, Nicolas Richard, and Guillaume Thouvenin
Subjects: medicine.medical_specialty, medicine.diagnostic_test, Adult patients, business.industry, Bilateral pleural effusion, Interstitial lung disease, Computed tomography, respiratory system, medicine.disease, respiratory tract diseases, Lung ultrasound, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Medicine, 030212 general & internal medicine, Radiology, business, Pleural line
Abstract: Introduction: Diagnosis and monitoring of interstitial lung disease (ILD) in children are mainly based on chest computed tomography (CT), resulting in significant exposure to x-rays. In adult patients, studies have shown a good sensitivity of the lung ultrasound (LUS) for detecting interstitial lesions, with a high correlation between LUS and CT images. The aim of this pilot study was to assess in children with ILD: (i) the feasibility of lung ultrasound and (ii) the comparability of LUS and CT images. Methods: LUS was performed in 5 children followed in the RespiRare® centre for an ILD of various aetiologies. Images visualized by LUS were described and compared to those seen at the latest chest CT. Results: The 5 children were 1.5, 2.5, 7, 11 and 16 years old respectively. Interstitial lesions were visualized by LUS in 4 of the 5 children, characterized by the presence of more than 3 confluent or spaced B lines per field, associated with an irregularity of the pleural line. Two children presented sub-pleural consolidations that were also seen on their CT. Bilateral pleural effusion was observed by LUS in one child. Only one child had a normal LUS while his CT showed some scattered micro-nodular lesions. Conclusion: This pilot study demonstrated a good correlation between LUS and CT images. As in adult patients, LUS could be an interesting tool for screening and monitoring children with ILD, reducing their exposure to x-rays in comparison to CT.
Published: 2020

40. COPA syndrome, 5 years after: Where are we?

Author: Nadia Nathan, Marie-Louise Frémond, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], and Couvet, Sandrine
Subjects: Lung Diseases, Heterozygote, Diffuse alveolar haemorrhage, Lupus nephritis, Mutation, Missense, Arthritis, Interstitial lung disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Coatomer Protein, Variable Expression, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, COPA, medicine, Missense mutation, Humans, 030212 general & internal medicine, 030203 arthritis & rheumatology, Lung, business.industry, Syndrome, medicine.disease, Phenotype, medicine.anatomical_structure, Immunology, Autoinflammation, Interferon, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Janus kinase, business
Abstract: Heterozygous missense mutations in COPA, encoding coatomer protein subunit alpha (COPA), cause an interferonopathy mainly associating lung, joint and kidney involvement. This rare autoinflammatory disease is characterised by variable expression and a remarkably high frequency of clinical non-penetrance. Lung features, predominantly chronic diffuse alveolar haemorrhage (DAH), are observed in almost patients and can result in end-stage respiratory insufficiency. The initially described phenotype was broadened to include isolated DAH or lupus nephritis. Rare manifestations reminiscent of other monogenic interferonopathies occur. This indicates the need for careful clinical evaluation in patients with suspicion or diagnosis of COPA syndrome. Considering the dominant inheritance model and the highly variable phenotype, ranging from severe multi-organic disorder to non-penetrance, a careful family screening is recommended. New insights in disease pathogenesis have linked COPA mutations to STING-mediated interferon signalling. Beside a variable efficacy of 'classical' immunosuppressive drugs, Janus kinase (JAK) inhibitors constitute a promising treatment in COPA syndrome, and further targeted therapies are awaited.
Published: 2020

41. Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling

Author: Nicolas Manel, Siham Boulisfane-El Khalifi, Mary Brennan, Darragh Duffy, Nadia Nathan, Serge Amselem, Kathryn J. McKenzie, Maria José Martin-Niclos, Jonny Hertzog, Carolina Uggenti, Marie Legendre, Stéphanie Chhun, Caroline Thumerelle, Luis Seabra, Marie-Louise Frémond, Vincent Bondet, Bénédicte Neven, Joseph A. Marsh, Marie Wislez, Catherine McDougall, Marine Depp, Jan Rehwinkel, Gillian I. Rice, Aurore Coulomb L'Hermine, Yanick J. Crow, Lucienne Chatenoud, Melvin Le Bihan, Thierry Jo Molina, Karen J. Mackenzie, Alice Lepelley, Edwin Carter, Jonathan Marey, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Radcliffe Department of Medicine [Oxford], University of Oxford [Oxford], Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Royal Hospital for Sick Children [Edinburgh], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de pathologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Royal Infirmary of Edinburgh, Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Service d'immuno-hématologie pédiatrique [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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), M.-L. Frémond received a grant from the Institut National de la Santé et de la Recherche Médicale (000427993) and acknowledges La Fondation Square. Y.J. Crow acknowledges the European Research Council (GA309449 and 786142-E-T1IFNs), and a state subsidy managed by the Agence Nationale de la Recherche under the 'Investments for the Future' program (ANR-10-IAHU-01). Y.J. Crow and D. Duffy acknowledge the Agence Nationale de la Recherche (grant CE17001002). J.A. Marsh is supported by a Medical Research Council Career Development Award (MR/M02122X/1) and is a Lister Institute of Preventive Medicine Research Prize Fellow. N. Manel was supported by LABEX DCBIOL (ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043), ANR-17-CE15-0025-01, ANR-18-CE92-0022-01, Fondation BMS, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ECTZ71745), Sidaction (VIH2016126002), and Ile-de-France Emergence. M. Le Bihan received a doctoral fellowship from Ile-de-France ARDoc. The project was supported by MSDAVENIR (Devo-Decode Project)., We thank Immunoqure AG for provision of antibodies for the Simoa assay., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-17-CE15-0025,STINGCHECK,Mécanismes des points de contrôle du senseur de l'immunité innée STING(2017), ANR-18-CE92-0022,cGAS-Vac,Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants(2018), European Project: 309449,EC:FP7:ERC,ERC-2012-StG_20111109,T1-IFN(2013), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), UF de Génétique moléculaire [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Vougny, Marie-Christine, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Mécanismes des points de contrôle du senseur de l'immunité innée STING - - STINGCHECK2017 - ANR-17-CE15-0025 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Analyses fonctionnelles de la voie cGAS/STING au cours d'infections bactériennes et infections virales et implications pour le développement de vaccins innovants - - cGAS-Vac2018 - ANR-18-CE92-0022 - AAPG2018 - VALID, and Definition and characterization of type I interferonopathies - T1-IFN - - EC:FP7:ERC2013-03-01 - 2018-02-28 - 309449 - VALID
Subjects: 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Protein subunit, Immunology, Mutant, Biology, medicine.disease_cause, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Interferon, medicine, Immunology and Allergy, Gene silencing, Mutation, HEK 293 cells, Golgi apparatus, eye diseases, 3. Good health, Cell biology, Sting, 030104 developmental biology, 030220 oncology & carcinogenesis, symbols, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug
Abstract: International audience; Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER-Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.
Published: 2020

42. The Wide Spectrum of COVID-19 Clinical Presentation in Children

Author: Julien Jegard, Aurélie Schnuriger, Guillaume Aubertin, Chiara Sileo, Thibault Lecarpentier, Harriet Corvol, Guillaume Thouvenin, Nicolas Richard, Jessica Taytard, Nadia Nathan, Blandine Prevost, Laura Berdah, Isabelle Guellec, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Mucoviscidose: physiopathologie et phénogénomique [CRSA], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Pediatrics, medicine.medical_specialty, Abdominal pain, [SDV]Life Sciences [q-bio], lcsh:Medicine, Context (language use), MIS-C, Disease, 030204 cardiovascular system & hematology, Overweight, Article, 03 medical and health sciences, 0302 clinical medicine, children, Medicine, 030212 general & internal medicine, business.industry, SARS-CoV-2, infants, lcsh:R, COVID-19, General Medicine, acute respiratory distress syndrome, medicine.disease, Obesity, Acute chest syndrome, 3. Good health, [SDV] Life Sciences [q-bio], Cohort, Presentation (obstetrics), medicine.symptom, business, PIMS-TS
Abstract: Background: Ten months after its appearance in December 2019, SARS-CoV-2 has infected more than 25 million patients worldwide. Because children were first identified as potential spreaders of the virus, schools were closed in several countries. However, it rapidly became evident that the number of hospitalized children infected by SARS-CoV-2 was dramatically lower than that of adults. To date, only hypotheses have been raised to explain this difference, so it is of great importance to describe the presentation of this disease among children. Here, we describe a wide spectrum of COVID-19 manifestation in children in a dedicated pediatric unit in France. Methods: Patients hospitalized with COVID-19 who were diagnosed on the basis of either positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs and/or typical aspects in chest-computed tomography (CT) were included between March and May 2020 in Paris. Results: Twenty-three patients were included on the basis of positive RT-PCR (n = 20) and/or typical aspects in CT (n = 4). The median age was 4.9 years [0.1&ndash, 17.6]. Patients were grouped by age (&lt, 2 years old: n = 14, 61%, 2&ndash, 10 years old: n = 2, 9%, &gt, 10 years old: n = 7, 30%). Overweight or obesity was reported in only three patients. At presentation, the most frequent symptom in the overall cohort was fever (n = 18, 78%), followed by acute rhinitis (n = 9, 64%) and cough (n = 7, 50%) in the under 2-year-old group and cough (n = 4, 57%), fatigue, dyspnea and abdominal pain (n = 3, 43% each) in the over 10-year-old group. Five patients required ICU treatment, four of whom were aged &gt, 10 years, two presented with acute myocarditis, and two were sickle cell disease patients who presented with acute chest syndrome. Discussion and conclusion: The youngest patients seem to present milder forms of COVID-19 without the need for ICU treatment and with a shorter length of hospitalization. More severe evolutions were observed in teenagers, with, however, favorable outcomes. Given the context of closed schools and confinement, the infection of these children suggests intra-familial transmission that needs to be further assessed. This description might help to understand the intriguing differences in COVID-19 severity across age-classes.
Published: 2020

43. Child–Adult Transition in Sarcoidosis: A Series of 52 Patients

Author: Simon Chauveau, Florence Jeny, Marie-Emeline Montagne, Rola Abou Taam, Véronique Houdouin, Ulrich Meinzer, Christophe Delacourt, Ralph Epaud, Fleur Cohen Aubart, Catherine Chapelon-Abric, Dominique Israël-Biet, Karine Juvin, Antoine Dossier, Bahram Bodaghi, Grégoire Prévot, Jean-Marc Naccache, Sarah Mattioni, Antoine Deschildre, Jacques Brouard, Abdellatif Tazi, Roderich Meckenstock, Morgane Didier, Julien Haroche, Annick Clement, Jean-François Bernaudin, Hilario Nunes, Dominique Valeyre, Nadia Nathan, and for the French Sarcoidosis Group (GSF)
Subjects: Pediatrics, medicine.medical_specialty, medicine.drug_class, Severe disease, lcsh:Medicine, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, children, transition of care, 0502 economics and business, medicine, sarcoidosis, Adverse effect, interstitial lung disease, Series (stratigraphy), Cumulative dose, business.industry, 05 social sciences, lcsh:R, Interstitial lung disease, General Medicine, medicine.disease, Corticosteroid, 050211 marketing, Sarcoidosis, business
Abstract: (1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (&le, 15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (&plusmn, 2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3&ndash, 44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0&ndash, 32), resulting in mostly mild (18, 35.3%) and rarely severe (2, 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood.
Published: 2020

44. Dramatic improvement after tocilizumab of severe COVID ‐19 in a child with sickle cell disease and acute chest syndrome

Author: Marie-Hélène Odièvre, Nadia Nathan, Hubert Ducou Le Pointe, Jenny Youn, Slimane Allali, Jessica Taytard, Anne Sophie Romain, Charles de Marcellus, and Harriet Corvol
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Cell, Disease, Hematology, medicine.disease, biology.organism_classification, Virology, Acute chest syndrome, chemistry.chemical_compound, medicine.anatomical_structure, Tocilizumab, chemistry, Pandemic, medicine, business, Betacoronavirus
Published: 2020
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45. Atypical presentation of COVID-19 in young infants

Author: Nadia Nathan, Blandine Prevost, and Harriet Corvol
Subjects: 2019-20 coronavirus outbreak, biology, Coronavirus disease 2019 (COVID-19), business.industry, General Medicine, biology.organism_classification, medicine.disease, medicine.disease_cause, Virology, Young infants, Pneumonia, Pandemic, Medicine, Presentation (obstetrics), business, Betacoronavirus, Coronavirus
Published: 2020
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46. Functional assessment and phenotypic heterogeneity of

Author: Marie, Legendre, Afifaa, Butt, Raphaël, Borie, Marie-Pierre, Debray, Diane, Bouvry, Emilie, Filhol-Blin, Tifenn, Desroziers, Valérie, Nau, Bruno, Copin, Florence, Dastot-Le Moal, Mélanie, Héry, Philippe, Duquesnoy, Nathalie, Allou, Anne, Bergeron, Julien, Bermudez, Aurélie, Cazes, Anne-Laure, Chene, Vincent, Cottin, Bruno, Crestani, Jean-Charles, Dalphin, Christine, Dombret, Bérénice, Doray, Clairelyne, Dupin, Violaine, Giraud, Anne, Gondouin, Laurent, Gouya, Dominique, Israël-Biet, Caroline, Kannengiesser, Aurélie, Le Borgne, Sylvie, Leroy, Elisabeth, Longchampt, Gwenaël, Lorillon, Hilario, Nunes, Clément, Picard, Martine, Reynaud-Gaubert, Julie, Traclet, Paul, de Vuyst, Aurore, Coulomb L'Hermine, Annick, Clement, Serge, Amselem, and Nadia, Nathan
Subjects: Adult, Lung Neoplasms, Adolescent, Pulmonary Surfactant-Associated Protein A, Infant, Middle Aged, Young Adult, Phenotype, Child, Preschool, Mutation, Humans, Child, Lung Diseases, Interstitial, Aged
Abstract: Interstitial lung diseases (ILDs) can be caused by mutations in theThe consequences of the 11For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic
Published: 2020

47. Genetic causes and clinical management of pediatric interstitial lung diseases

Author: Nadia Nathan, Keren Borensztajn, Annick Clement, Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], and Couvet, Sandrine
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Pulmonary Surfactant-Associated Proteins, Genetic counseling, Thyroid Nuclear Factor 1, Genetic Counseling, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pathogenesis, 03 medical and health sciences, High morbidity, 0302 clinical medicine, medicine, Humans, Genetic Testing, Respiratory system, Child, Genetic testing, Lung, Heterogeneous group, medicine.diagnostic_test, business.industry, Granulocyte-Macrophage Colony-Stimulating Factor, respiratory system, respiratory tract diseases, Phenotype, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030228 respiratory system, Lung disease, Mutation, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, ATP-Binding Cassette Transporters, Lung Diseases, Interstitial, business
Abstract: Purpose of review: Interstitial lung disease (ILD) in children (chILD) is an umbrella term for a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and implicates genetic contributors. The purpose of this review is to provide updated information on the molecular defects associated with the development of chILD.Recent findings: Currently, the main mutations are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, and NKX2-1. In addition, pulmonary alveolar proteinosis is associated with mutations in CSF2RA, CSF2RB, and MARS, and specific auto-inflammatory forms of chILD implicate STING and COPA disorders. The relationships between the genetic defects and the disease expression remain poorly understood, with no genotype-phenotype correlations identified so far. Although targeted therapies are emerging, the management strategies are still largely empirical, relying mostly on corticosteroids.Summary: Genetic factors play an important role in chILD, and the ongoing development of novel technologies will rapidly broaden the genetic landscape of chILD. Therefore, in the coming years, it is expected that newly identified molecular defects and markers will help predicting disease courses and tailoring individual therapies.
Published: 2018

48. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

Author: Annick Clement, Yves Pacheco, Jean-François Bernaudin, Gilles Devouassoux, Adrien Buisson, Clarice X. Lim, Dominique Valeyre, Vincent Cottin, Claire Bardel, Alain Calender, Serge Lebecque, Pascal Sève, Pierre Antoine Rollat Farnier, Stéphane Pinson, Harriet Corvol, Abderrazzaq Bentaher, Pascal Roy, Rola Abou Taam, Thomas Weichhart, Nadia Nathan, Véronique Houdouin, Service de Génétique [CHU Lyon] (Centre de pathologie de l'Est), Hospices civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA 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), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie [Hôpital Croix Rousse, CHU Lyon], Hôpital de la Croix-Rousse [CHU Lyon], Service de Pneumologie [Hôpital Louis Pradel – CHU Lyon] (Centre de Référence des Maladies Pulmonaires Rares), CHU Lyon-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Médecine Interne [Hôpital Croix Rousse, CHU Lyon], CHU Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Service d'histologie et biologie des tumeurs [CHU Tenon] (ER2-UPMC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Center for Pathobiochemistry and Genetics [Vienna, Austria], Institute of Medical Genetics [Vienna, Austria]-Medizinische Universität Wien = Medical University of Vienna, Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Communautés d’universités et établissements Sorbonne Paris Cité (COMUE Sorbonne Paris Cité), Université Sorbonne Paris Cité (USPC)-Chimie ParisTech-Université Paris sciences et lettres (PSL), Service de Pneumologie [AP-HP Hôpital Avicenne, Bobigny], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), This study was performed with the grant named ‘High Throughput sequencing and rare disease’ from the 'Fondation Maladies Rares' (FMR - France) and financial support from the INNOVARC - DGOS ref. 12–027-0309., GSF (Groupe Sarcoïdose France), CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris 13 (UP13), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-CHU Lyon, Medizinische Universität Wien = Medical University of Vienna-Institute of Medical Genetics [Vienna, Austria], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), BMC, BMC, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP]
Subjects: Male, 0301 basic medicine, Proband, Candidate gene, lcsh:Internal medicine, Sarcoidosis, lcsh:QH426-470, [SDV]Life Sciences [q-bio], Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Candidate genes, 03 medical and health sciences, Exome Sequencing, Genetics, Humans, Allele, Child, lcsh:RC31-1245, Gene, Exome, Genetics (clinical), Exome sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, Genetic Variation, Whole-exome sequencing (WES), Human genetics, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], lcsh:Genetics, 030104 developmental biology, Female, Genome-Wide Association Study, Research Article
Abstract: Background Sarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To find out relevant sarcoidosis predisposing genes, we searched for de novo and recessive mutations in 3 young probands with sarcoidosis and their healthy parents using a whole-exome sequencing (WES) methodology. Methods From the SARCFAM project based on a national network collecting familial cases of sarcoidosis, we selected three families (trios) in which a child, despite healthy parents, develop the disease before age 15 yr. Each trio was genotyped by WES (Illumina HiSEQ 2500) and we selected the gene variants segregating as 1) new mutations only occurring in affected children and 2) as recessive traits transmitted from each parents. The identified coding variants were compared between the three families. Allelic frequencies and in silico functional results were analyzed using ExAC, SIFT and Polyphenv2 databases. The clinical and genetic studies were registered by the ClinicalTrials.gov - Protocol Registration and Results System (PRS) (https://clinicaltrials.gov) receipt under the reference NCT02829853 and has been approved by the ethical committee (CPP LYON SUD EST – 2 – REF IRB 00009118 – September 21, 2016). Results We identified 37 genes sharing coding variants occurring either as recessive mutations in at least 2 trios or de novo mutations in one of the three affected children. The genes were classified according to their potential roles in immunity related pathways: 9 to autophagy and intracellular trafficking, 6 to G-proteins regulation, 4 to T-cell activation, 4 to cell cycle and immune synapse, 2 to innate immunity. Ten of the 37 genes were studied in a bibliographic way to evaluate the functional link with sarcoidosis. Conclusions Whole exome analysis of case-parent trios is useful for the identification of genes predisposing to complex genetic diseases as sarcoidosis. Our data identified 37 genes that could be putatively linked to a pediatric form of sarcoidosis in three trios. Our in-depth focus on 10 of these 37 genes may suggest that the formation of the characteristic lesion in sarcoidosis, granuloma, results from combined deficits in autophagy and intracellular trafficking (ex: Sec16A, AP5B1 and RREB1), G-proteins regulation (ex: OBSCN, CTTND2 and DNAH11), T-cell activation (ex: IDO2, IGSF3), mitosis and/or immune synapse (ex: SPICE1 and KNL1). The significance of these findings needs to be confirmed by functional tests on selected gene variants. Electronic supplementary material The online version of this article (10.1186/s12920-018-0338-x) contains supplementary material, which is available to authorized users.
Published: 2018

49. Cohorte française du syndrome COPA

Author: Nadia Nathan, Alexandre Belot, C. Thumerelle, Yanick J. Crow, Marie-Louise Frémond, S. El khalifi, Brigitte Bader-Meunier, M. Wislez, and C. David
Subjects: Rheumatology, Gastroenterology, Internal Medicine
Published: 2021

50. Présentations hétérogènes des mutations du gène NK2 homeobox 1, implications en pratique clinique

Author: Isabelle Gibertini, Sylvain Marchand-Adam, X. Li, and Nadia Nathan
Subjects: Pulmonary and Respiratory Medicine
Abstract: Introduction Le gene NK2 homeobox 1 (NKX2-1) code pour le facteur-1 de transcription de la thyroide (TTF-1). Il s’agit d’un regulateur de la transcription de genes au niveau de la thyroide, du cerveau et du poumon. Une mutation autosomique dominante heterozygote de ce gene peut etre responsable de diverses atteintes isolees ou associees entre elles a des degres varies. Methodes Nous rapportons plusieurs cas de patients avec mutation du gene NKX2-1 de presentation heterogene. Resultats Dans le 1er cas, le diagnostic de syndrome cerveau–thyroide–poumon est pose a 21 ans. Ce jeune homme avait une hypothyroidie congenitale et des troubles neurologiques apparus a l’âge de 12 mois, a type de mouvements choreiques d’etiologie inconnue. En 2017, asymptomatique sur le plan respiratoire, il a beneficie de facon fortuite d’un scanner thoracique montrant d’importantes plages en verre depoli, disseminees sur l’ensemble du poumon. Devant ces anomalies radiologiques, une mutation heterozygote du gene NKX2-1 a ete decouverte. Le 2e cas est celui d’une fillette âgee de 10 mois, hospitalisee pour une gastro-enterite aigue et une polypnee severe. Le scanner thoracique retrouvait un aspect en mosaique des poumons avec la presence de plages en verre depoli mal systematisees. Une analyse systematique du gene NKX2-1 a retrouve une mutation au niveau du cadre du travail. Le pere de cette fillette, sans aucun antecedent pulmonaire ni thyroidien est hospitalise au meme moment a l’âge de 30 ans a l’occasion d’une pneumopathie virale severe. Son scanner thoracique montrait des plages en verre depoli mal limitees des deux champs pulmonaires ainsi que des images kystiques diffuses. La meme mutation du gene NKX2-1 que sa fille est retrouvee. La grand-mere paternelle de la fillette etait decedee a l’âge de 46 ans, dans les suites d’un adenocarcinome pulmonaire TTF-1 negatif, survenu sur une fibrose pulmonaire atypique et severe diagnostiquee a l’âge de 31 ans. Il est a noter qu’aucune des personnes de cette famille n’a presente d’atteinte thyroidienne ou neurologique. Conclusion En conclusion, les patients avec mutations du gene NKX2-1 peuvent avoir des presentations cliniques heterogenes. Celles-ci doivent etre prises en consideration pour le conseil genetique et la prise en charge des patients.
Published: 2020

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