Necrotizing pneumonia in children: Report of 25 cases between 2008 and 2018 at a French tertiary care center.

BACKGROUND: Necrotizing pneumonia (NP) is a serious and rare disease in children. Pediatric data on NP are limited and the impact of the 13-valent pneumococcal conjugate vaccine has been very poorly evaluated. PATIENTS AND METHODS: We conducted a retrospective study at Toulouse University Hospital between 2008 and 2018. Children who presented with thin-walled cavities in the areas of parenchymal consolidation on imaging were included in the study. RESULTS: The incidence of NP did not decrease during this period. Bacterial identification occurred in 56% of cases (14/25) and included six cases of Streptococcus pneumoniae, five of Staphylococcus aureus, two of Streptococcus pyogenes, and one of Streptococcus viridans. Streptococcus pneumoniae NP are more frequently associated with empyema/parapneumonic effusion compared to S. aureus NP (p = 0.02). Patients with S. pyogenes NP more often required volume expansion than did S. pneumoniae cases (p = 0.03). When comparing children born before and after implementation of the 13-valent pneumococcal conjugate vaccine, we identified a relative modification of the bacterial epidemiology, with an increase in the proportion of S. pyogenes NP and S. aureus NP and a decrease in the proportion of NP caused by S. pneumoniae. CONCLUSION: Future studies are needed to assess the epidemiology of NP in children. Continued surveillance of identified pneumococcal serotypes is essential to document epidemiological changes in the coming years.

COBRAPed cohort: Do sensitization patterns differentiate children with severe asthma from those with a milder disease?

BACKGROUND: It is unclear whether sensitization patterns differentiate children with severe recurrent wheeze (SRW)/severe asthma (SA) from those with non-severe recurrent wheeze (NSRW)/non-severe asthma (NSA). Our objective was to determine whether sensitization patterns can discriminate between children from the French COBRAPed cohort with NSRW/NSA and those with SRW/SA. METHODS: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschools (3-6 years) and 170 school-age children (7-12 years). Supervised analyses and clustering methods were applied to identify patterns of sensitization among children with positive c-sIgE. RESULTS: We observed c-sIgE sensitization in 51% of preschool and 75% of school-age children. Sensitization to house dust mite (HDM) components was more frequent among NSRW than SRW (53% vs. 24%, p < .01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs. 4%, p < .01) and associated with an FEV1/FVC < -1.64 z-score. Among sensitized children, seven clusters with varying patterns were identified. The two broader clusters identified in each age group were characterized by "few sensitizations, mainly to HDM." One cluster (n = 4) with "multiple sensitizations, mainly to grass pollen, HDM, PR-10, and nsLTP" was associated with SA in school-age children. CONCLUSIONS: Although children with wheeze/asthma display frequent occurrences and high levels of sensitization, sensitization patterns did not provide strong signals to discriminate children with severe disease from those with milder disease. These results suggest that the severity of wheeze/asthma may depend on both IgE- and non-IgE-mediated mechanisms.

Successful Elective Thoracoscopic Resection of Complicate Extralobar Bronchopulmonary Sequestration after Intrafoetal Vascular Laser Ablation: The Paediatric Surgeon's Point of View.

Few reports of laser coagulation for foetal bronchopulmonary sequestration (BPS), a rare congenital malformation characterised by the absence of tracheobronchial connection and the presence of a systemic feeding artery, have been published. Additionally, very few of them focus also on the postnatal management, with results limited and controversial. Postnatal treatment of residual malformation remains debated, hence the need to share our experience of a combined pre- and postnatal approach to complicated extra-lobar BPS. We report the case of a female foetus with the diagnosis of a pulmonary lesion. Due to mediastinal shift, unilateral compressive hydrothorax, ascites, and hydrops, a foetal treatment with ultrasound-guided laser coagulation of the anomalous vessel was performed. At birth, due to the persistence of the malformation, an elective delayed thoracoscopical surgery was performed. Prenatal laser ablation for complicated BPS is a life-saving procedure not always resulting in lesion disappearance. Thoracoscopical surgical exploration in case of persistent lesions at birth offers the possibility of a minimally invasive sequestrectomy feasible and safe.

Diffuse alveolar haemorrhage in children: an international multicentre study.

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.

[Transition from pediatric to adult care in chronic respiratory diseases: The cystic fibrosis model]. / Transition des patients atteints d'une maladie respiratoire chronique depuis la pédiatrie vers les services pour adultes - L'exemple de la mucoviscidose.

Increased life expectancy in cystic fibrosis has made transition from pediatric to adult cystic fibrosis centers a crucial step for patients, their families and caregivers. This transition must be gradual and carefully prepared. A formalized process, early discussion with patients and families about transition, patient's empowerment prior to transfer, and close links between pediatric and adult teams are key points to succeed. Therapeutic education, validated questionnaires, personalized action plans or connected tools can help. Transfer will take place at the appropriate time for each patient, ideally during a period of disease stability, in a progressive manner, with joint or alternating consultations between pediatric and adult cystic fibrosis center teams. Other chronic respiratory diseases with pediatric onset may benefit from similar transition processes.

Title: Transition des patients atteints d'une maladie respiratoire chronique depuis la pédiatrie vers les services pour adultes - L'exemple de la mucoviscidose. Abstract: Du fait de l'augmentation de l'espérance de vie des individus atteints de mucoviscidose, la transition de la pédiatrie vers les services de médecine pour adultes est devenue une étape essentielle pour les patients, les aidants et les soignants. Cette transition doit être progressive et longuement préparée. Avoir un processus établi et formalisé, aborder tôt le thème de la transition avec le patient et sa famille, autonomiser le patient avant le transfert et établir des liens étroits entre les structures médicales pédiatriques et pour adultes sont des éléments importants pour la réussite de cette étape. L'éducation thérapeutique ainsi que l'utilisation de questionnaires validés, d'un plan d'action personnalisé ou d'outils connectés peuvent aider. Le transfert se fera au moment le mieux adapté pour le patient, idéalement en période de stabilité de la maladie, de manière progressive, avec des consultations conjointes ou alternées entre les équipes de pédiatrie et de médecine pour adultes. D'autres maladies respiratoires chroniques débutant dans l'enfance ou à l'adolescence pourront bénéficier d'un processus de transition similaire.

Predicting the risk of respiratory distress in newborns with congenital pulmonary malformations.

OBJECTIVES: Most children with prenatally diagnosed congenital pulmonary malformations (CPMs) are asymptomatic at birth. We aimed to develop a parsimonious prognostic model for predicting the risk of neonatal respiratory distress (NRD) in preterm and term infants with CPM, based on the prenatal attributes of the malformation. METHODS: MALFPULM is a prospective population-based nationally representative cohort including 436 pregnant women. The main predictive variable was the CPM volume ratio (CVR) measured at diagnosis (CVR first) and the highest CVR measured (CVR max). Separate models were estimated for preterm and term infants and were validated by bootstrapping. RESULTS: In total, 67 of the 383 neonates studied (17%) had NRD. For infants born at term (>37 weeks, n=351), the most parsimonious model included CVR max as the only predictive variable (receiver operating characteristic (ROC) curve area: 0.70±0.04, negative predictive value: 0.91). The probability of NRD increased linearly with increasing CVR max and remained below 10% for CVR max <0.4. In preterm infants (n=32), both CVR max and gestational age were important predictors of the risk of NRD (ROC: 0.85±0.07). Models based on CVR first had a similar predictive ability. CONCLUSIONS: Predictive models based exclusively on CVR measurements had a high negative predictive value in infants born at term. Our study results could contribute to the individualised general risk assessment to guide decisions about the need for newborns with prenatally diagnosed CPM to be delivered at specialised centres.

Long-Term Outcomes in Real Life of Lumacaftor-Ivacaftor Treatment in Adolescents With Cystic Fibrosis.

Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment. Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12-18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients. Results: Forty adolescents aged 12.0-17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated. Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.

Pediatrician intervention impacts parental smoking in cystic fibrosis, diabetes, and bronchiolitis.

BACKGROUND: Child exposure to cigarette smoke is harmful. It should be reduced through parental smoking cessation interventions. The aim of our study was to determine the impact of simple advice provided by the pediatrician on the smoking habits of parents of children with cystic fibrosis (CF), diabetes mellitus (DM), and infants hospitalized for bronchiolitis. METHODS: Parents were interviewed on their smoking habits. Smoking cessation advice was provided by the pediatrician. A new smoking habits assessment was done at 3 months by phone interviews. RESULTS: A total of 260 parents were interviewed (91 in the CF group, 136 in the DM group, and 33 in the bronchiolitis group). A total of 70 parents were active smokers: 33% of parents of children with CF, 23.5% of parents of children with DM, and 24.2% for those with infants hospitalized for bronchiolitis (p = .42). In the CF group, smoking cessation had been significantly more frequently discussed with the medical team previously. A total of 67 smoking parents (95.7%) answered the 3-month assessment: 29.8% reported having started a smoking cessation process; 10.4% had quit smoking. The quitting rate was significantly higher in the groups of patients followed for a respiratory disorder (37.5% for bronchiolitis, 15% for CF vs. 0% for DM, p = .005). CONCLUSION: This study shows the important role that information and simple advice from pediatricians can have in initiating smoking cessation in parents of patients followed in specialized clinics or who are hospitalized, with a greater efficiency in parents of patients suffering from lung disorders.

Pulmonary Alveolar Microlithiasis in Children Less than 5 Years of Age.

OBJECTIVE: To collect all published cases up to January 2019 of pulmonary alveolar microlithiasis (PAM) in patients age 5 years and under and to compare their characteristics with those of the 1022 cases in the most recent all-age cohort published in 2015. STUDY DESIGN: We identified 28 cases of PAM worldwide in children age 5 years and under, accounting for only 2%-3% of all cases. RESULTS: Children seem more frequently symptomatic, notably with more cough and severe acute respiratory failure, but had no reported extrapulmonary manifestation. Children with PAM evidenced less typical radiologic findings, with frequent ground glass opacities not reported in adult cases and milder calcifications as less frequent, smaller, and mainly restricted to the lower lobes. CONCLUSIONS: PAM remains an uncommon diagnosis in young children, as symptoms and radiologic findings are less specific. Physicians should be aware to look for calcifications in chest computed tomography at mediastinal window and avoid elution of the bronchoalveolar lavage to find microliths. Collecting longitudinal data through an international registry would help in characterizing PAM to predict disease progression and plan lung transplantation.