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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 <2.466), as was the level of serum IFNα (211 fg/mL, healthy <10 fg/mL). STAT1 phosphorylation in T lymphocytes and monocytes was increased as compared with healthy controls. Based on these results she was treated with the JAK1/2 inhibitor ruxolitinib, which resulted in reduction in IFN signalling and appeared to be associated with partial though incomplete decrease in the severity of her pulmonary disease. Patients with alveolar haemorrhage of unknown origin should be considered for COPA screening. Functional tests can help to personalise patient therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Recent data has shown that lung inflammation and infection subvene very early in very young infants with Cystic Fibrosis (CF). This leads to impaired lung function and structural damage, even in asymptomatic children. In the CF-pig model constitutional airway narrowing is present at birth, and is associated with defective mucus migration, and impaired bacterial clearance. At the age of 3 months, 25% of screened CF infants show decreased lung function. Air trapping is also present in 68% and bronchiectasis in 28% of patients. At the same age, the presence of neutrophil elastase in the bronchoalveolar lavage is an ominous sign since it triples the risk of bronchiectasis at the age of 3 years. Since only very few drug therapies have been validated in the preschool children, adapted clinical trials are warranted in this age group. Early interventions may have a huge impact on the natural history of CF, on the condition of not interfering with normal lung growth., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3months of age tripled the risk of bronchiectasis at the age of 3years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

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.

The objective of this study was to evaluate the predictive value of the respiratory system compliance (Crs) and resistance (Rrs) measured before surfactant therapy to identify infants at risk for chronic lung disease (CLD). Measurements of Crs and Rrs were obtained on 44 ventilated neonates with respiratory distress syndrome (RDS) before and after surfactant therapy using the passive expiratory flow-volume method. It was found that in addition to a lower gestational age (GA) and a lower birth weight (BW), infants with CLD (n = 10) exhibited a lower Pa/AO(2) [Pa/AO(2) = PaO(2)/(PiO(2) - PaCO(2))] and higher Rrs before surfactant compared to the infants without CLD (n = 28). Improvement in gas exchange 18 h after surfactant was reduced in the CLD group. Finally, we concluded that a low GA (< 28 weeks), a low BW (< 942 g), a low Pa/AO(2) before and 18 h after surfactant or a high Rrs before surfactant (>0.21 cm H(2)O/ml/s) were associated with an increased risk of CLD., (Copyright 2003 S. Karger AG, Basel)

Abstract: Systemic or inhaled steroids are regularly prescribed to the preterm infant, since the incidence of bronchopulmonary dysplasia remains high. Their short-term beneficial effects should be weighed against their potentially very severe long-term deleterious effects. Their impact on lung growth and development is time-, dose- and steroid dependent, although this has been less well studied compared to the brain. Dexamethasone has been shown to be the most high-risk molecule, but given that the other steroid agents have not been proved entirely innocuous, further randomized studies are urgently required. [Copyright &y& Elsevier]

Summary: Persistent and dysregulated inflammation, combined with an exaggerated host response is a major contributor to CF lung disease. As lung disease progresses, neutrophil accumulation in the airways ensues. Modulation of CF airway inflammation may result in either beneficial or deleterious side effects, resulting in more harm than good. Antibiotics, in particular, macrolides which act as a long-term anti-inflammatory agent with an excellent safety profile, and dornase alpha, are very interesting agents; steroids are not indicated in CF except in very special situations, and other promising agents such as leukotriene modifiers, high-dose N-acetylcysteine, anti-elastase and anti-cytokines require further research. Research should focus on early treatment, before lung damage has occurred [Copyright &y& Elsevier]