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Introduction: Childhood Interstitial Lung Disease (chILD) represents a rare and severe group of diseases for which the etiologic workup, classification, and management remain a challenge for most pediatric pulmonologists. In France in 2018, the RespiRare network established the first multidisciplinary team meetings (MDTm) dedicated to chILD. This study aims to investigate the impact of MDTm in chILD diagnosis and management as well as user satisfaction., Methods: The MDTm took place on a monthly basis through video conferences. The participants consisted of a quorum and included pediatric pulmonologists, radiologists, geneticists, and pulmonologists, with an average of 10.5 participants per meeting. Patients provided consent to participate in MDTm and for data collection. Data were retrospectively extracted from MDTm reports. To evaluate the usefulness of the MDTm and the satisfaction of the participants, a survey was sent by email at least 3 months after the MDTm to the participants., Results: A total of 216 chILD cases were discussed during 56 MDTm sessions. The median age of onset was 0.5 years (interquartile range 0-7). The MDTm sessions resulted in the correction of chILD etiology in 25% of cases (neuroendocrine cell hyperplasia of infancy 17%, surfactant metabolism disorder 8%, pulmonary alveolar proteinosis 4%, hemosiderosis 3%, sarcoidosis 3%, and others 34%), and chILD was ruled out in 7% of cases. A change in therapy was proposed for 46% of cases. User satisfaction was significant, particularly regarding their confidence in managing these rare diseases., Discussion and Conclusion: Dedicated MDTm sessions offer a unique opportunity to enhance chILD etiologic diagnosis and management, leading to increased physician knowledge and confidence in managing these patients., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Patients with inherited pulmonary surfactant metabolism disorders have a wide range of clinical outcomes and imaging findings. Response to current anti-inflammatory therapies has been variable and efficacy is unclear., Objective: To describe and compare genetic, clinical, histological, and computed tomography (CT) outcomes in a cohort of patients with variants in the genes encoding surfactant protein C (SP-C) or adenosine triphosphate-binding cassette transporter A3 (ABCA3) in Argentina., Methods: Observational cohort retrospective study. Patients carrying variants in genes encoding SP-C and ABCA3 proteins were included., Results: Fourteen patients met the inclusion criteria: SFTPC n = 6, ABCA3 n = 8 (seven were heterozygous and one compound heterozygous). Neonatal respiratory distress was more frequent and severe in neonates with variants in the ABCA3 gene. The onset of the disease occurred in infancy before the age of 20 months in all cases. Patients with ABCA3 pathogenic variants had a severe clinical course, while long-term outcomes were more favorable in individuals with SFTPC variants. Initial CT findings were ground glass opacities and intraparenchymal cysts in both groups. Over time, signs of lung fibrosis were present in 57% of patients with ABCA3 variants and in 33% of the SFTPC group. The efficacy of anti-inflammatory interventions appears to be poor, especially for patients with ABCA3 pathogenic variants., Conclusions: Clinical, histological, and radiological features are similar in patients with SFTPC and ABCA3 variants; however, the latter have more severe clinical course. Current anti-inflammatory regimens do not appear to stop the progression of the disease., (© 2022 Wiley Periodicals LLC.)

Introduction: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED)., Methods: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority., Results: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France., Discussion: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay., (© 2021 Wiley Periodicals LLC.)

Introduction: COVID-19 pandemic and associated lockdown measures have deeply modified the natural course of seasonal viral infections, such as respiratory syncytial virus (RSV)., Methods: We analyzed French national data from three networks: emergency departments (ED) of French hospitals, general practitioners (GP), and hospital laboratories. We compared the number of ED or GP visits for bronchiolitis in children <2 years of age, and the percentage of RSV positive tests in the 2020 to 2021 season with those of the two previous seasons (2018-2019 and 2019-2020). We used time series of the previous 5 years to calculate epidemic thresholds., Results: During the 2020-2021 season, the epidemic begun in February (Week 05) in the Ile de France (Paris and suburbs) region, 12 weeks later compared with the previous seasons and progressively spread across all the French metropolitan regions. The highest number of bronchiolitis cases in 2021 (Week 12) occurred 10-12 weeks after the previous seasonal peaks of previous seasons, but the number of cases remained lower than in the previous seasonal peaks., Conclusion: We identified a delayed RSV epidemic in the period that usually corresponds at the end of the epidemic season, raising concerns for the burden of RSV in the already strained healthcare systems during the COVID-19 pandemic., (© 2021 Wiley Periodicals LLC.)

The 2019 novel coronavirus (SARS-CoV-2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence-based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID-19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control., (© 2020 Wiley Periodicals, Inc.)

Introduction: Interstitial lung disease in children (chILD) is a highly heterogeneous group of rare and severe respiratory disorders. The disease by itself, the burden of the treatments (oxygen therapy, corticosteroid pulses, nutritional support) and recurrent hospitalizations may impair the quality of life (QoL) of these children. The aim of the study was to compare the health-related QoL (HR-QoL) in chILD compared to a healthy population and to find out the predictive factors of an altered QoL., Methods: Patients aged 1 month to 18 years with ILD of known or unknown etiology were prospectively included. Parents and children over 8 years old were asked to fill the PedsQL 4.0 Generic Core Scale ranging from 0 to 100 points., Results: A total of 78 children were recruited in 13 French pediatric centers. Total scores were 11.94 points (P = 0.0003) less for child self-report and 14.08 points ( P < 0.0001) less for parent proxy-report with respect to the healthy population. The clinical factors associated with a lower total score were: extrapulmonary expression of the disease, higher Fan severity score, long-term oxygen therapy, nutritional support, and a number of oral treatments., Conclusion: Using a validated quality of life (QoL) scale, we showed that health-related-QoL is significantly impaired in chILD compared with a healthy population. Factors altering QoL score are easy to recognize and could help identify children at a heightened risk of low QoL., (© 2019 Wiley Periodicals, Inc.)

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that is caused by mutations in mainly two genes, that is ENG, encoding endoglin (HHT1), or ACVRL1, encoding activin receptor-like kinase 1 (ALK-1/HHT2). HHT is characterized by recurrent epistaxis, mucocutaneous telangiectasia, and vascular visceral dysplasia responsible for visceral arteriovenous malformations (AVM)., Aim: to report the experience of two university hospitals (Trousseau, Paris, and CHIC, Creteil) with screening children for HHT and pulmonary AVM (PAVM) using high resolution computed tomography (HRCT)., Methods: parents with confirmed HHT were offered to have their children screened for the mutation identified in their family, and informed consent was obtained. Children carrying the same mutation as their parents underwent HRCT of the chest without contrast., Results: between 2008 and 2015, 99 children were screened for HHT mutations. Mutations were identified in 59 patients, that is 24 HHT1 and 35 HHT2. Radiologic and clinical screening was possible in 52 patients (21 HHT-1 and 31 HHT-2). Among those, PAVM was identified in 13 patients (25%; n = 8 HHT1; n = 5 HHT2), and four of them required embolization therapy., Conclusion: This study highlights the usefulness of genetic screening in children with known HHT family. It also suggests that a non-invasive protocol such as HRTC is an efficient approach to detect non-symptomatic lesions that are present early on in children carrying the ENG (HHT1), but also the ACVRL1 mutations (HHT2). Pediatr Pulmonol. 2017;52:642-649. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Introduction: There is a lack of evidence concerning the effectiveness of immunoprophylaxis with palivizumab in children with childhood interstitial lung disease (chILD). In this retrospective study, we evaluated the effectiveness of palivizumab for decreasing the rate of RSV-related hospitalizations in children under the age of 24 months with chILD treated with corticosteroids., Methods: A retrospective national study was conducted in France. Patients born between 2007 and 2013, diagnosed with chILD and on corticosteroid treatment were identified through the French online database for pediatric interstitial lung disease (Respirare(®) ). Data were collected for the etiology and severity of chILD, risk factors and preventive measures for bronchiolitis, palivizumab immunoprophylaxis, and hospitalizations for bronchiolitis and RSV-bronchiolitis., Results: We included and evaluated 24 children during their first two RSV seasons, corresponding to 36 patient-seasons. The observed rate of RSV-related hospitalization (305/1000 patient-seasons), and the median length of stay (7 days), were higher than those for the general population. RSV-related hospitalization rates did not differ significantly between children with and without palivizumab prophylaxis (5/16 vs. 4/18, respectively, P = 0.70)., Conclusion: Children with chILD on corticosteroid treatment are at high risk of hospitalization for RSV-bronchiolitis, which tends to be more severe in these children than in the general population. The effectiveness of palivizumab prophylaxis in this population remains to be demonstrated. Pediatr Pulmonol. 2016;51:688-695. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Rationale: High-resolution computed tomography (HRCT) plays an important role in the diagnosis and staging of pulmonary sarcoidosis, but implies radiation exposure. In this light, we aimed to describe HRCT findings as well as their relationship with pulmonary function tests (PFT) in children with pulmonary sarcoidosis., Methods: In a retrospective study, 18 pediatric patients with sarcoidosis, including 12 with pulmonary abnormalities (PA group) and 6 without pulmonary abnormalities (APA group) were followed over a 16-year period. Relationships between HRCT scores and PFT were studied by non-parametric Spearman's test at diagnosis and by restricted maximum likelihood (REML) analysis during follow-up., Results: Forty-three HRCT were scored. Twelve patients showed abnormal HRCT findings at diagnosis with multiple nodules or micronodules, while ground-glass opacities were seen in 11 patients. Ten patients exhibited pleural thickening or thickening of the fissure and 6 had interlobular septal thickening at diagnosis. No correlation between HRCT and forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the mid-half of the FVC (FEF(25-75)) and specific dynamical compliance (SpecC(Ldyn)) was found at diagnosis. However, linear mixed models showed that changes in total HRCT scores over time were significantly associated with SpecC(Ldyn), FVC, and FEV1 modifications., Conclusion: Radiologic findings in children with pulmonary sarcoidosis were similar to those in adults. HRCT and PFT are both essential investigations at diagnosis; however, the correlation between HRCT pulmonary parenchymal findings and PFT over time suggests the possibility of reducing the number of HRCT during follow-up to decrease unnecessary radiation exposure., (© 2013 Wiley Periodicals, Inc.)

Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as autosomal traits with variable penetrance and severity or as sporadic disease caused by a de novo mutation on one allele. Here, we report the case of a child surviving with a homozygous surfactant protein C mutation after aggressive clinical management unlike his six siblings who died in infancy. This presentation raises the suspicion of an autosomal recessive inheritance that is discussed in this report., (© 2013 Wiley Periodicals, Inc.)

Aim of the Study: Determine high-resolution tomography (HRCT) scan characteristics in children with SFTPC mutation and correlate them to histological findings., Patients and Methods: This retrospective multicenter study included 15 children (7 females and 8 males) with SFTPC mutations. HRCT scans have been performed in all the children and lung biopsies in 8 children., Results: From all signs assessed on initial HRCT scans, ground-glass opacities (n =14, 93%) and lung cysts (n = 6, 40%) were predominant. Interlobular septal thickening (n = 1, 7%), air space consolidation (n = 1, 7%), paraseptal emphysema (n = 2, 13%), and pulmonary nodules (n = 1, 7%) were also found. Histological analysis revealed accumulation of macrophages in the alveolar lumen, type II pneumocyte hyperplasia, and alveolar septal thickening. Dilatation of the respiratory bronchiole and alveolar duct associated with muscular hyperplasia were also described. Interestingly, lung cysts on HRCT scans were associated with dilatation of terminal bronchioli and alveolar duct in lung biopsies., Conclusion: In children with SFTPC mutations, HRCT scan finding was highly correlated to the histological findings and, as such, represent a useful tool to identify patients that may require SFTPC gene sequencing., (© 2010 Wiley-Liss, Inc.)

Congenital chondroid lesions of the lung are rare pathological findings. They are a constant feature of lung malformations such as giant cystic pulmonary chondroid hamartoma, chondroid cystic malformation, and in the "cartilaginous variant" of congenital adenomatoid malformation. All of these present as a large single thoracic mass.We present the cases of three males and two females with hitherto undescribed diffuse chondroid lung disease, all but one of whom had neonatal respiratory distress syndrome with interstitial syndrome on chest radiograph. The pathological findings were similar in all patients, showing large areas of disorganized lung parenchyma containing diffusely distributed mature cartilage islands. With a mean follow-up of 6 years, all patients had a favorable outcome. This diffuse chondroid lung disease appears to be a new entity whose initial presentation mimicked interstitial lung disease without the usual clinical, radiological, and histological features. We speculate that it could be part of a clinical spectrum between malformative chondroid lung cyst and congenital pulmonary airway malformation.

NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB and SFTPC, respectively). We identified and functionally characterized two new de novo NKX2-1 mutations c.493C>T (p.R165W) and c.786&#95;787del2 (p.L263fs) in infants with closely similar severe interstitial lung disease (ILD), hypotonia, and congenital hypothyroidism. Functional analyses using A549 and HeLa cells revealed that NKX2-1-p.L263fs induced neither SFTPB nor SFTPC promoter activation and had a dominant negative effect on wild-type (WT) NKX2-1. In contrast,NKX2-1-p.R165W activated SFTPC, to a significantly greater extent than did WTNKX2-1, while SFTPB activation was only significantly reduced in HeLa cells. In accordance with our in vitro data, we found decreased amounts of SP-B and SP-C by western blot in bronchoalveolar lavage fluid (patient with p.L263fs) and features of altered surfactant protein metabolism on lung histology (patient with NKX2-1-p.R165W). In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in "Brain-Lung-Thyroid syndrome"., ((c) 2009 Wiley-Liss, Inc.)

Objectives: To describe the long-term course and the management in children of chronic interstitial lung disease associated with I73T mutation., Materials and Methods: Clinical, radiological, and histological data from one family including five children and two adults were analyzed retrospectively for three patients and prospectively for the others., Results: Mean age of onset of respiratory symptoms for children was 6 months (2-15 months). The follow up was 14 months to 15 years (mean 55 months). The children were treated by intravenous high dose methylprednisolone pulses (6-15, mean 12). Four received oral prednisolone (mean 16 months) and hydroxychloroquine, one of these had additional mycophenolate mofetil. One adult with mild respiratory symptoms in infancy and another who was symptom free were also diagnosed. Both of them received no treatment. BAL fluids were obtained in all children: pro-SPC and SPB were positive in all. Lung biopsies were performed in two children respectively at 7 months, showing interstitial pneumonia features with endoluminal macrophage and type II alveolar cells hyperplasia, and at 33 months, showing subpleural microbullae, areas of interstitial pneumonia and type II alveolar cells hyperplasia. Immunohistochemistry showed for both an increased SPB and TTF1 staining in type II cells nuclei and a faint staining for pro-SPC and for ABCA3. Genetic diagnosis obviated the need for biopsy in other cases. The clinical status progressively improved and oxygen supplementation could be stopped after 3-14 months (mean 9 months). The CT scans initially showed ground glass opacities, then reduction in the ground glass pattern associated with clinical improvement and development of cysts., Conclusion: This kindred illustrates the variability of respiratory involvement and prognosis. It confirms the value of genetic screening for surfactant protein genes mutations., ((c) 2009 Wiley-Liss, Inc.)