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Homozygous or compound heterozygous for frameshift or nonsense mutations in the ATP–binding cassette transporter A3 (ABCA3) is associated with neonatal respiratory failure and death within the first year of life without lung transplantation. We report the case of a newborn baby girl who developed severe respiratory distress soon after birth. She was diagnosed with compound heterozygous frameshift mutation of the ABCA3 gene. Despite extensive treatment (intravenous corticosteroids pulse therapy, oral corticosteroids, azithromycin, and hydroxychloroquine), she developed chronic respiratory failure. As the parents refused cardio-pulmonary transplantation and couldn't resolve to an accompaniment of end of life, a tracheostomy was performed resulting in continuous mechanical ventilation. A neurodevelopmental delay and an overall muscular dystrophy were noted. At the age of 5 years, after 2 episodes of pneumothorax, the patient died from severe respiratory failure. To our knowledge, this was the first case of a child with compound heterozygous frameshift mutation who posed such an ethical dilemma with a patient surviving till the age of five years. [ABSTRACT FROM AUTHOR]

La crise d’asthme aigue¨ grave se de´finit comme une crise d’asthme qui ne re´pond pas au traitement d’urgence bronchodilatateur et qui est responsable d’une insuffisance respiratoire aigue¨ engageant le pronostic vital. La morbidite´ lie´e a` ces crises est non ne´gligeable et la physiopathologie permet de distinguer deux tableaux. Le premier, rapidement progressif, ou` l’inflammation et l’hypere´osinophilie pre´dominent et le deuxie`me, tre`s brutal, avec une composante spastique majeure. Dans tous les cas, les points cle´s de la prise en charge sont une reconnaissance rapide et un traitement agressif. L’utilisation de glucocorticoi¨des par voie syste´mique, d’ae´rosols de beˆta 2-agonistes et l’oxyge´nothe´rapie est la cle´ de vouˆte du traitement auquel vient s’ajouter le bromure d’inatropium. D’autres outils the´rapeutiques sont utilise´s en cas de re´sistance au traitement habituel mais ne´cessitent un monitorage strict en soins intensifs. Ce sont notamment le sulfate de magne´sium, la ke´tamine, l’he´liox et les gaz anesthe´siques. Une fois l’e´pisode controˆle´, il convient dans tous les cas de prescrire ou de renforcer le traitement de fond qui sera associe´ a` une e´ducation du patient et de sa famille. [Copyright 2003 Elsevier]

Abstract Background Interstitial lung diseases (ILDs) in children represent a heterogeneous group of rare respiratory disorders that affect the lung parenchyma. After the launch of the French Reference Centre for Rare Lung Diseases (RespiRare®), we created a national network and a web-linked database to collect data on pediatric ILD. Methods Since 2008, the database has been set up in all RespiRare® centres. After patient's parents' oral consent is obtained, physicians enter the data of children with ILD: identity, social data and environmental data; specific aetiological diagnosis of the ILD if known, genetics, patient visits to the centre, and all medical examinations and tests done for the diagnosis and/or during follow up. Each participating centre has a free access to his own patients' data only, and cross-centre studies require mutual agreement. Physicians may use the system as a daily aid for patient care through a web-linked medical file, backed on this database. Results Data was collected for 205 cases of ILD. The M/F sex ratio was 0.9. Median age at diagnosis was 1.5 years old [0–16.9]. A specific aetiology was identified in 149 (72.7%) patients while 56 (27.3%) cases remain undiagnosed. Surfactant deficiencies and alveolar proteinosis, haemosiderosis, and sarcoidosis represent almost half of the diagnoses. Median length of follow-up is 2.9 years [0–17.2]. Conclusions We introduce here the French network and the largest national database in pediatric ILDs. The diagnosis spectrum and the estimated incidence are consistent with other European databases. An important challenge will be to reduce the proportion of unclassified ILDs by a standardized diagnosis work-up. This database is a great opportunity to improve patient care and disease pathogenesis knowledge. A European network including physicians and European foundations is now emerging with the initial aim of devising a simplified European database/register as a first step to larger European studies.

Abstract Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy.

Abstract Objective To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children. Study design Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009. Results 21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications. Conclusion Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.

Abstract Background Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R). Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent deleterious effects of oxygen exposure. Methods Since IGF-1R null mutant mice die at birth from respiratory failure, we generated compound heterozygous mice harboring a hypomorphic (Igf-1rneo) and a knockout (Igf-1r-) receptor allele. These IGF-1Rneo/- mice, strongly deficient in IGF-1R, were subjected to hyperoxia and analyzed for survival time, ventilatory control, pulmonary histopathology, morphometry, lung edema and vascular permeability. Results Strikingly, after 72 h of exposure to 90% O2, IGF-1Rneo/- mice had a significantly better survival rate during recovery than IGF-1R+/+ mice (77% versus 53%, P < 0.05). The pulmonary injury was consistently, and significantly, milder in IGF-1Rneo/- mice which developed conspicuously less edema and vascular extravasation than controls. Also, hyperoxia-induced abnormal pattern of breathing which precipitated respiratory failure was elicited less frequently in the IGF-1Rneo/- mice. Conclusion Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury.

Objectif Décrire la fréquence et l’aspect en imagerie des anomalies abdominales de la sarcoïdose. Matériels et méthodes Etude rétrospective (1994-2014) incluant les 22 patients (1-15 ans) suivis dans notre établissement pour une sarcoïdose prouvée histologiquement. Lors du bilan initial tous ont été explorés par une échographie (19) ou une tomodensitométrie (TDM) de l’abdomen (3) et une TDM thoracique (22). Résultats Des anomalies radiologiques abdominales ont été retrouvées dans 11 des 22 patients, l’atteinte abdominale étant révélatrice de la maladie dans 6 cas. L’atteinte abdominale était systématiquement associée à une atteinte thoracique ganglionnaire (8) et/ou parenchymateuse (10). Les anomalies retrouvées étaient : hépatomégalie homogène, hétérogène ou nodulaire (8), splénomégalie homogène, hétérogène ou nodulaire (4), adénopathies (6). En raison d’une symptomatologie clinique, 2/11 patients ont bénéficié d’une endoscopie digestive haute mettant en évidence une atteinte gastrique à l’histologie, l’un des 2 avait aussi une atteinte biologique pancréatique, sans anomalie gastrique ou pancréatique à l’imagerie dans les 2 cas. Conclusion Dans notre série l’atteinte abdominale est associée à l’atteinte thoracique. Les principales lésions sont hépatospléniques et ganglionnaires. [ABSTRACT FROM AUTHOR]

Ménétrier's disease is a protein-losing gastropathy that is uncommon in childhood. Its symptoms are unspecific, with abdominal pain, vomiting, and edema. Blood tests show hypoproteinemia and hypoalbuminemia, and upper digestive endoscopy reveals giant gastric folds. In children, cytomegalovirus has been identified as a possible cause. Here we describe two sisters presenting with Ménétrier's disease, 2 years apart. This diagnosis should be considered in the presence of hypoalbuminemia in children when a nephrotic syndrome is excluded. [ABSTRACT FROM AUTHOR]

Objectifs Déterminer si une prophylaxie par palivizumab permettait de réduire le taux d’hospitalisation pour bronchiolite à virus respiratoire syncitial (VRS) chez les enfants de moins de 2 ans traités par corticothérapie systémique dans le cadre d’une pneumopathie interstitielle sévère. Matériels et méthodes Étude rétrospective nationale à partir de la base de données Respirare , chez les enfants nés entre le 1/1/2007 et le 1/1/2014. Les données étaient collectées à partir des dossiers médicaux et des carnets de santé. Résultats principaux Vingt-quatre enfants ont été inclus et évalués sur 2 saisons épidémiques, représentant 36 enfants–saisons. Le taux d’hospitalisation pour bronchiolite à VRS, 305 pour 1000 enfants–saisons, était très supérieur à celui de la population générale. Il n’existait pas de différence quant aux taux d’hospitalisation pour bronchiolite à VRS entre les enfants traités par palivizumab et les enfants non traités (respectivement 7/18 versus 4/18, p 0,47). Conclusions Les enfants suivis pour pneumopathie interstitielle et traités par corticothérapie systémique sont sujets à des bronchiolites à VRS plus fréquentes et plus graves, dont la prévention par le palivizumab reste à démontrer. [ABSTRACT FROM AUTHOR]