Background: Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. Classically, diagnosis is based on a triad including hemoptysis, diffuse parenchymal infiltrates on chest X-rays, and iron-deficiency anemia. We present the French pediatric cohort of IPH collected through the French Reference Center for Rare Lung Diseases (RespiRare®,http://www.respirare.fr).Methods: Since 2008, a national network/web-linked RespiRare® database has been set up in 12 French pediatric respiratory centres. It is structured as a medical recording tool with extended disease-specific datasets containing clinical information relevant to all forms of rare lung diseases including IPH.Results: We identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0] yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16, 64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n = 11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung biopsy (6/25). In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%). All the patients were initially treated by corticosteroids. In 13 cases, immunosuppressants were introduced due to corticoresistance and/or major side effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage.Conclusion: The present cohort provides substantial information on clinical expression and outcomes of pediatric IPH. Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors.

Objective To evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1). Methods Patients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children9s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32). Results We treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment (p < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 (SMN2) gene. Conclusions Our results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease. ClinicalTrials.gov identifier: NCT02865109. Classification of evidence This study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.

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Background: While the prevalence of Stenotrophomonas maltophilia lung infection in cystic fibrosis (CF) patients has increased in the last decades, its pathogenicity remains controversial. The aim of this study was to investigate the effects of S. maltophilia initial infection on the progression of lung disease in CF children.Methods: This case‐control retrospective study took place in a pediatric CF center. A total of 23 cases defined by at least one sputum culture positive for S. maltophilia, were matched for age, sex, and CFTR mutations to 23 never infected CF controls. The clinical data were collected for 2 years before and after S. maltophilia initial infection and comprised lung function analyses, rates of exacerbations and of antibiotic courses.Results: Compared with controls, cases had lower lung function (P = 0.05), more frequent pulmonary exacerbations (P = 0.01), hospitalizations (P = 0.02), and intravenous antibiotic courses (P = 0.04) before S. maltophilia acquisition. In the year following S. maltophilia initial infection, lung function decline was similar in cases and controls but cases remained more severe, with more frequent pulmonary exacerbations (P = 0.01), hospitalizations (P = 0.02) and intravenous antibiotic courses (P = 0.02).Conclusions: S. maltophilia seems to be a marker of CF lung disease severity and international recommendations to reduce lung infection by this pathogen should rapidly emerge.