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

First analysis of the Severe Paediatric Asthma Collaborative in Europe registry.

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe. Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination. Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic. We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching

Airway-artery quantitative assessment on chest computed tomography in paediatric primary ciliary dyskinesia

Chest computed tomography (CT) is the gold standard for detecting structural abnormalities in patients with primary ciliary dyskinesia (PCD) such as bronchiectasis, bronchial wall thickening and mucus plugging. There are no studies on quantitative assessment of airway and artery abnormalities in children with PCD. The objectives of the present study were to quantify airway and artery dimensions on chest CT in a cohort of children with PCD and compare these with control children to analyse the influence of covariates on airway and artery dimensions. Chest CTs of 13 children with PCD (14 CT scans) and 12 control children were collected retrospectively. The bronchial tree was segmented semi-automatically and reconstructed in a three-dimensional view. All visible airway-artery (AA) pairs were measured perpendicular to the airway centre line, annotating per branch inner and outer airway and adjacent artery diameter and computing inner airway diameter/artery ratio (AinA ratio), outer airway diameter/artery ratio (AoutA ratio), wall thickness (WT), WT/outer airway diameter ratio (Awt ratio) and WT/artery ratio. In the children with PCD (38.5% male, mean age 13.5 years, range 9.8-15.3) 1526 AA pairs were measured versus 1516 in controls (58.3% male, mean age 13.5 years, range 8-14.8). AinA ratio and AoutA ratio were significantly higher in children with PCD than in control children (both p<0.001). Awt ratio was significantly higher in control children than in children with PCD (p<0.001). Our study showed that in children with PCD airways are more dilated than in controls and do not show airway wall thickening

Lung structure and function on MRI in preterm born school children with and without BPD: A feasibility study

Background and Objective The most common respiratory complication of prematurity is bronchopulmonary dysplasia (BPD), leading to structural lung changes and impaired respiratory outcomes. However, also preterm children without BPD may show similar adverse respiratory outcomes. There is a need for a safe imaging modality for preterm children with and without BPD for disease severity assessment and risk stratification. Our objective was to develop a magnetic resonance imaging (MRI) protocol in preterm children with and without BPD at school age. Methods Nine healthy volunteers (median age 11.6 [range: 8.8–12.8] years), 11 preterm children with BPD (11.0 [7.2–15.6] years), and 9 without BPD (11.1 [10.7–12.6] years) underwent MRI. Images were scored on hypo- and hyperintense abnormalities, bronchopathy, and architectural distortion. MRI data were correlated to spirometry. Ventilation and perfusion defects were analyzed using Fourier Decomposition (FD) MRI. Results On MRI, children with BPD had higher %diseased lung (9.1 (interquartile range [IQR] 5.9–11.6)%) compared to preterm children without BPD (3.4 (IQR 2.5–5.4)%, p < 0.001) and healthy volunteers (0.4 (IQR 0.1–0.8)%, p < 0.001). %Diseased lung correlated negatively with %predicted FEV1 (r = −0.40, p = 0.04), FEV1/FVC (r = −0.49, p = 0.009) and FEF75 (r = −0.63, p < 0.001). Ventilation and perfusion defects on FD sequence corresponded to hypointense regions on expiratory MRI. Conclusion Chest MRI can identify structural and functional lung damage at school age in preterm children with and without BPD, showing a good correlation with spirometry. We propose MRI as a sensitive and safe imaging method (without ionizing radiation, contrast agents, or the use of anesthesia) for the long-term follow-up of preterm children

Small airways targeted treatment with smart nebulizer technology could improve severe asthma in children: a retrospective analysis

Objective: Conventional inhaler devices have a low efficacy in targeting small airways. Smart nebulizers can be used to increase deposition to small airways by adjusting the flow and depth of each inhalation based on patients ‘individual inspiratory capacity. We investigated whether targeting of high dose inhaled corticosteroids (ICS) to small airways with a smart nebulizer could reduce exacerbation rate in children with severe asthma (SA). Methods: We conducted a retrospective study in children with SA using a smart nebulizer (Akita® Jet nebulizer) for the administration of high dose ICS in our outpatient clinic at the Erasmus MC — Sophia Children’s Hospital. Clinical data before and after start of treatment were collected. The primary outcome was exacerbation rate, defined as: number of asthma exacerbations for which oral corticosteroid courses (OCS) were prescribed. The exacerbation rate 1 year before treatment was compared with the exacerbation rate 1 year after start of treatment. Secondary outcomes were changes in spirometry parameters, hospital admissions and medication use. Results: Data on OCS use was available for 28/31 patients. Median number of asthma exacerbations requiring OCS courses 1 year before decreased from 2 (interquartile range(IQR) 2) to 0.5 (IQR 3) 1 year after treatment (p = 0.021). Hospital admission decreased from 1 (IQR 3) to 0 (IQR 1)(p = 0.028). FEV1, FEF25-75 and FEF75 were not significantly improved after one year of treatment with the smart nebulizer (p = 0.191; p = 0.248; p = 0.572). Conclusion: Targeting small airways with high dose ICS using a smart nebulizer resulted in a significant reduction in exacerbations requiring OCS after one year of treatment

ERS International Congress 2020: highlights from the Paediatric Assembly

In this review, the Paediatric Assembly of the European Respiratory Society (ERS) presents a summary of the highlights and most relevant findings in the field of paediatric respiratory medicine presented at the virtual ERS International Congress 2020. Early Career Members of the ERS and Chairs of the different Groups comprising the Paediatric Assembly discuss a selection of the presented research. These cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, epidemiology, bronchology and lung and airway development. Specifically, we describe the long-term effect in lung function of premature birth, mode of delivery and chronic respiratory conditions such as cystic fibrosis. In paediatric asthma, we present risk factors, phenotypes and their progression with age, and the challenges in diagnosis. We confirm the value of the lung clearance index to detect early lung changes in cystic fibrosis. For bronchiectasis treatment, we highlight the importance of identifying treatable traits. The use of biomarkers and genotypes to identify infants at risk of long-term respiratory morbidity is also discussed. We present the long-term impact on respiratory health of early life and fetal exposures to maternal obesity and intrauterine hypoxia, mechanical ventilation hyperoxia, aeroallergens, air pollution, vitamin A deficient intake and bronchitis. Moreover, we report on the use of metabolomics and genetic analysis to understand the effect of these exposures on lung growth and alveolar development. Finally, we stress the need to establish multidisciplinary teams to treat complex airway pathologies

Pediatric long‐COVID: An overlooked phenomenon?

BACKGROUND: Long‐COVID is a well‐documented multisystem disease in adults. Far less is known about long‐term sequelae of COVID in children. Here, we report on the occurrence of long‐COVID in Dutch children. PATIENTS AND METHODS: We conducted a national survey asking Dutch pediatricians to share their experiences on long‐COVID in children. We furthermore describe a case series of six children with long‐COVID to explore the clinical features in greater detail. RESULTS: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2–18 years, suspected of long‐COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post‐COVID complaints. CONCLUSION: Our study shows that long‐COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management

Pediatric long-COVID: An overlooked phenomenon?

Background: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children. Patients and Methods: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail. Results: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2–18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints. Conclusion: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management

Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care

Objectives To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. Methods Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. Results Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. Conclusion This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned

ERS International Congress 2021 virtual: highlights from the Paediatric Assembly.

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the Assembly 7 – Paediatrics Groups, present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The Groups cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, 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 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