Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres: expert practical experience and advice.

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition.This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient's journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

[Treatment of tracheo(broncho)malacia in children]. / Comment je traite la trachéo(broncho)malacie de l'enfant ?

Tracheomalacia (TM) is characterized by tracheal collapse due to an intrinsic anomaly resulting in a lack of rigidity of the cartilaginous rings and/or the posterior membrane during expiration, coughing or crying. It may also be secondary to external compression or acquired during endobronchial diseases. TM is commonly associated with other syndromes or airway abnormalities. Tracheomalacia can be localized or diffused and if the main bronchi are involved, the term of tracheobronchomalacia (TBM) is used. The most common symptoms include expiratory stridor, barking cough and recurrent respiratory tract infections. If tracheal weakness is severe, Acute Life Threating Events (ALTE) or Brief Resolved Unexplained Event (BRUE) can occur. While mild forms usually do not require any treatment, severe TBM may require medical and/or surgical management. Amongst several possible treatments, including tracheostomy, noninvasive ventilation and airway stenting, the pexy surgical approach (posterior, anterior tracheopexy or aortopexy) is currently the favoured option.

La trachéomalacie (TM) est caractérisée par un collapsus trachéal plus ou moins important durant l'expiration, lors des efforts de toux ou des pleurs. Elle peut être due à une anomalie intrinsèque, par manque de rigidité des anneaux cartilagineux et/ou de la membrane postérieure. Elle peut aussi avoir une origine extrinsèque, soit secondaire à une compression externe, soit acquise dans le cadre de pathologies endo-bronchiques. Elle peut enfin être associée à certains syndromes ou malformations des voies respiratoires. La TM peut être localisée ou généralisée, et si les bronches principales sont atteintes, on parlera de trachéobronchomalacie (TBM). Les symptômes les plus courants sont : un stridor expiratoire, une toux aboyante, et des infections respiratoires récurrentes. Dans les cas les plus sévères, des événements menaçant la vie de l'enfant (Acute Life-Threatening Event «ALTE¼ ou Brief Resolved Unexplained Event «BRUE¼) peuvent survenir. Alors que les formes légères ne requièrent généralement pas de traitement, la TBM sévère peut nécessiter une prise en charge médicale et/ou chirurgicale. Parmi les divers choix thérapeutiques, incluant notamment la trachéostomie, la ventilation non invasive et les stents trachéaux, l'approche chirurgicale par pexie (aortopexie, trachéopexie postérieure ou antérieure) est actuellement l'option favorite.

Diffuse alveolar hemorrhage in infants: Report of five cases.

Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition in children. In this entity, the bleeding originates from the pulmonary microvasculature as a result of microvascular damage leading to blood leakage into the alveolar spaces. DAH can occur as an isolated medical entity or may be associated with other organ system injury or dysfunction. The classic triad of symptoms includes hemoptysis, anemia and diffuse pulmonary infiltrates. Hemoptysis is the usual presenting symptom but is not constant. A variety of diseases is associated with the development of DAH. Current classification organize the etiologies of diffuse alveolar hemorrhage based on the presence of severe immune disorders (such as systemic vasculitis and collagenosis) or non-immunodeficiency disorders (with an identified cardiac or non-cardiac origin, or idiopathic). The five cases of DAH presented in this study were all diagnosed in full-term infants, four males and one female, with normal neonatal adaptation and without family history of notable diseases. In all cases the diagnosis was made between the age of three and eighteen weeks-old. Moreover, all five patients, at the time of diagnosis, presented with hemoptysis, mild or severe dyspnea, anemia and abnormal chest X-rays. Consequently, the diagnosis of DAH was strongly suspected and, eventually, confirmed by bronchoscopy. Additional laboratory tests, as well as selected serologic and radiographic studies were performed in order to identify a specific etiology. The final diagnoses reflect a variety of causes: infections, idiopathic pulmonary hemosiderosis, accidental suffocation and Heiner syndrome. Treatment included oral corticosteroids except from one patient that received antimicrobial therapy.

[News drugs and evolution towards personalized treatment for cystic fibrosis]. / Avancées thérapeutiques et évolution vers une médecine personnalisée pour les patients atteints de mucoviscidose.

Cystic fibrosis is a genetic disorder responsible for the production of a defective transmembrane protein. In recent years, new protein modulators have been developed. They aim to treat the underlying cause of the disease. The results on the biomarkers of the function of the CFTR protein and on the clinical outcomes are very encouraging. However, there is an individual heterogeneity in the response to modulators within a same genotype. Furthermore, clinical trials focus on the most common mutations in the CFTR gene, in particular DF508. Intestinal organoids, a new model of ex vivo study, could offer a quick approach to increase access to effective treatment for all patients with cystic fibrosis regardless of their CFTR genotype. Organoids could enable personalized treatment of cystic fibrosis.

La mucoviscidose est une maladie génétique responsable de la production d'une protéine transmembranaire défectueuse. Au cours des dernières années, se sont développés des traitements modulateurs ciblant les défauts spécifiques de la protéine causés par les mutations du gène CFTR. Les résultats sur les biomarqueurs de la fonction de la protéine CFTR et sur les paramètres cliniques sont très encourageants. Cependant, une hétérogénéité individuelle dans la réponse aux modulateurs est observée. De plus, les essais cliniques se focalisent sur les mutations les plus fréquentes du gène, en particulier DF508. Les organoïdes intestinaux, un nouveau modèle d'étude ex vivo, pourraient offrir une approche rapide pour majorer l'accès à un traitement efficace à tous les patients, quel que soit leur génotype CFTR. Les tests in vitro sur les organoïdes rendent possible l'évolution vers une médecine personnalisée pour les patients atteints de mucoviscidose.

[Retrospective study of childhood lymphomas. Report of 27 children treated at a single institution]. / Etude rétrospective des lymphomes de l'enfant. A propos de 27 cas traités dans une même institution.

Childhood lymphomas represent a heterogeneous group of disorders that are quite different from adult lymphomas. Over the past three decades, empirical chemotherapeutic management has transformed survival figures, and more recently greater understanding of the biology is offering hope for improved management of resistant disease. We present here the experience of a single institution in the management of 27 childhood lymphomas; epidemiological and clinical characteristics are described as well as survival rates. The median follow up of the patients is 4 years 7 months. The five-year overall survival for the entire group is more than 95 %; the 5-year disease free survival is 91,6 % for Hodgkin's lymphomas, 92,8% for non Hodgkin's lymphomas and 100% for Burkitt diseases. Two relapses have occurred and all of them appeared within the 18 months of the diagnosis. No toxic death has been reported.