Chest CT scoring for evaluation of lung sequelae in congenital diaphragmatic hernia survivors

Objectives Data on long-term structural lung abnormalities in survivors of congenital diaphragmatic hernia (CDH) is scarce. The purpose of this study was to develop a chest computed tomography (CT) score to assess the structural lung sequelae in CDH survivors and to study the correlation between the CT scoring and clinical parameters in the neonatal period and at 1 year of follow-up. Methods A prospective, clinical follow-up program is organised for CDH survivors at the University Hospital of Leuven including a chest CT at the age of 1 year. The CT scoring used and evaluated, named CDH-CT score, was adapted from the revised Aukland score for chronic lung disease of prematurity. Results Thirty-five patients were included. All CT scans showed some pulmonary abnormalities, ranging from very mild to severe. The mean total CT score was 16 (IQR: 9-23), with the greatest contribution from the subscores for decreased attenuation (5; IQR: 2-8), subpleural linear and triangular opacities (4; IQR: 3-5), and atelectasis/consolidation (2; IQR: 1-3). Interobserver and intraobserver agreement was very good for the total score (ICC coefficient > 0.9). Total CT score correlated with number of neonatal days ventilated/on oxygen as well as with respiratory symptoms and feeding problems at 1 year of age. Conclusion The CDH-CT scoring tool has a good intraobserver and interobserver repeatability and correlates with relevant clinical parameters. This holds promise for its use in clinical follow-up and as outcome parameter in clinical interventional studies

Bronchial Mucoepidermoid Carcinoma

A 12-year-old boy with chronic respiratory complaints, including cough, exercise intolerance, and persistent wheezing, was referred to our hospital because of persistent symptoms under extensive asthma therapy. A standard radiograph of the chest detected very slight hyperinflation of the left lung with increased lung translucency (Figure 1). Computed tomography revealed a polypoid mass distally in the left main bronchus with a density around 55 HU and very slightly decreased attenuation of the left lung, probably due to secondary air trapping (Figure 2). Bronchoscopy confirmed this finding, and biopsy revealed the mass to be a low-grade mucoepidermoid carcinoma (Figure 3). A curative bronchial sleeve resection was performed with partial mediastinal lymphadenectomy. All lymph nodes were normal, and there is no recurrence to this date (one year). Adjuvant chemotherapy was not indicated

Pulmonary function testing in children's interstitial lung disease

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials

Genomics of an endemic cystic fibrosis Burkholderia multivorans strain reveals low within-patient evolution but high between-patient diversity

In many countries, Burkholderia multivorans is the most prevalent species within the Burkholderia cepacia complex (Bcc) found infecting the lungs of patients with cystic fibrosis (CF). Its positive identification is of immediate concern to the health of the patient as it is notoriously hard to eradicate using antibiotics and can cause necrosis of the lung tissues (cepacia syndrome). Infection control measures reduced the prevalence of B. cenocepacia in CF wards, but patients continue to acquire infections by B. multivorans from environmental sources. In most reported cases, the infecting strains are unique except in rare cases in which cross-infection is observed between patients. We report here an endemic strain of B. multivorans with sequence type ST-742 that has been infecting multiple patients, without evidence for cross-infection. We investigated the epidemiology and genomics of this ST-742 strain and show that it is microdiverse, as isolates between-patients exhibit numerous genomic differences, at scales that have not been observed previously when looking at evolutionary trajectories within-patients. Additionally, we found that the specific genomic background of a given strain may dictate the strategy of adaptation within the CF lung. Burkholderia multivorans is a member of the Burkholderia cepacia complex (Bcc), notorious for its pathogenicity in persons with cystic fibrosis. Epidemiological surveillance suggests that patients predominantly acquire B. multivorans from environmental sources, with rare cases of patient-to-patient transmission. Here we report on the genomic analysis of thirteen isolates from an endemic B. multivorans strain infecting four cystic fibrosis patients treated in different pediatric cystic fibrosis centers in Belgium, with no evidence of cross-infection. All isolates share an identical sequence type (ST-742) but whole genome analysis shows that they exhibit peculiar patterns of genomic diversity between patients. By combining short and long reads sequencing technologies, we highlight key differences in terms of small nucleotide polymorphisms indicative of low rates of adaptive evolution within patient, and well-defined, hundred Kbps-long segments of high enrichment in mutations between patients. In addition, we observed large structural genomic variations amongst the isolates which revealed different plasmid contents, active roles for transposase IS3 and IS5 in the deactivation of genes, and mobile prophage elements. Our study shows limited within-patient B. multivorans evolution and high between-patient strain diversity, indicating that an environmental microdiverse reservoir must be present for this endemic strain, in which active diversification is taking place. Furthermore, our analysis also reveals a set of 30 parallel adaptations across multiple patients, indicating that the specific genomic background of a given strain may dictate the route of adaptation within the cystic fibrosis lung

ERS International Congress 2021: highlights from the Paediatric Assembly

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets

Quality standards for managing children and adolescents with bronchiectasis: an international consensus

The global burden of bronchiectasis in children and adolescents is being recognised increasingly. However, marked inequity exists between, and within, settings and countries for resources and standards of care afforded to children and adolescents with bronchiectasis compared with those with other chronic lung diseases. The European Respiratory Society (ERS) clinical practice guideline for the management of bronchiectasis in children and adolescents was published recently. Here we present an international consensus of quality standards of care for children and adolescents with bronchiectasis based upon this guideline. The panel used a standardised approach that included a Delphi process with 201 respondents from the parents and patients’ survey, and 299 physicians (across 54 countries) who care for children and adolescents with bronchiectasis. The seven quality standards of care statements developed by the panel address the current absence of quality standards for clinical care related to paediatric bronchiectasis. These internationally derived, clinician-, parent-and patient-informed, consensus-based quality standards statements can be used by parents and patients to access and advocate for quality care for their children and themselves, respectively. They can also be used by healthcare professionals to advocate for their patients, and by health services as a monitoring tool, to help optimise health outcomes.</p

Updated guidance on the management of children with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID)

Over the past two decades there has been considerable progress with the evaluation and management of infants with an inconclusive diagnosis following Newborn Screening (NBS) for cystic Fibrosis (CF). In addition, we have an increasing amount of evidence on which to base guidance on the management of these infants and, importantly, we have a consistent designation being used across the globe of CRMS/CFSPID. There is still work to be undertaken and research questions to answer, but these infants now receive more consistent and appropriate care pathways than previously. It is clear that the majority of these infants remain healthy, do not convert to a diagnosis of CF in childhood, and advice on management should reflect this. However, it is also clear that some will convert to a CF diagnosis and monitoring of these infants should facilitate their early recognition. Those infants that do not convert to a CF diagnosis have some potential of developing a CFTR-RD later in life. At present, it is not possible to quantify this risk, but families need to be provided with clear information of what to look out for. This paper contains a number of changes from previous guidance in light of developing evidence, but the major change is the recommendation of a detailed assessment of the child with CRMS/CFSPID in the sixth year of age, including respiratory function assessment and imaging. With these data, the CF team can discuss future care arrangements with the family and come to a shared decision on the best way forward, which may include discharge to primary care with appropriate information. Information is key for these families, and we recommend consideration of a further appointment when the individual is a young adult to directly communicate the implications of the CRMS/CFSPID designation

Faut-il un dépistage néonatal de la mucoviscidose en Belgique ?

ill.A la demande du Centre fédéral d'expertise des soins de santé (KCE), une équipe de pédiatres, d’experts en dépistage néonatal, en droit médical et en éthique, ont analysé les avantages et les inconvénients d’un dépistage systématique de la mucoviscidose chez tous les nouveau-nés. Le KCE ne recommande ce dépistage que si certaines conditions sont remplies: l’autorisation des parents après qu’ils aient été dûment informés, le contrôle de qualité des tests de dépistage, l’exécution sélective de tests génétiques et la garantie d’un suivi de qualit

Is Neonatale Screening op Mucoviscidose aangewezen in België ?

IX, 172 p.ill.In opdracht van het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) onderzocht een team van kinderartsen, experts in neonatale screening, medisch recht en ethiek de voor- en nadelen van het systematisch testen van alle pasgeborenen op mucoviscidose. Het KCE beveelt deze screening enkel aan indien aan welbepaalde voorwaarden wordt voldaan: de toestemming van de vooraf geïnformeerde ouders, de kwaliteitsbewaking van de screeningtesten, het selectief uitvoeren van genetische testen en garanties op kwaliteitsvolle opvolging achteraf

Best practices in the treatment of early cystic fibrosis lung disease

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized