[Pediatric pneumological aspects in the care of children with neuromuscular diseases with focus on Duchenne muscular dystrophy].

Duchenne muscular dystrophy is the most common inherited neuromuscular disease in children. In addition to the progressive loss of motor skills and cardiac involvement, respiratory muscle weakness leads to a restrictive lung disease and cough insufficiency. Specific respiratory interventions have significantly improved survival and quality of life of the affected boys.

Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections.

Background: Humans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm).

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

Introduction: Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma.

17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma.

The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes. To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus. Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.

Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells.

A single population of interferon-regulatory factor 8 (Irf8)-dependent conventional dendritic cell (cDC type1) is considered to be responsible for both immunogenic and tolerogenic responses depending on the surrounding cytokine . Here, we challenge this concept of an omnipotent single Irf8-dependent cDC1 cluster through analysis of pulmonary cDCs at single cell resolution. We report existence of a pulmonary cDC1 cluster lacking Xcr1 with an immunogenic signature that clearly differs from the Xcr1 positive cDC1 cluster.

Tracheostomy decannulation in children: a proposal for a structured approach on behalf of the working group chronic respiratory insufficiency within the German-speaking society of pediatric pulmonology.

The number of children with tracheostomies with and without home mechanical ventilation has grown continuously in recent years. For some of these children, the need for tracheostomy resolves and the child can be weaned from the tracheal cannula. Choosing the optimal time point for decannulation after elaborated prior diagnostic work-up needs careful consideration.

Validation of the Asthma Severity Scoring System (ASSESS) in the ALLIANCE Cohort.

Background: The Asthma Severity Scoring System (ASSESS) quantifies asthma severity in adolescents and adults. Scale performance in children younger than 12 years is unknown.

Objective: To validate the ASSESS score in the All Age Asthma Cohort and explore its use in children younger than 12 years.

Quality Control of Nitrogen Multiple Breath Washout in a Multicenter Pediatric Asthma Study.

Background: Nitrogen multiple breath washout (N2MBW) is a lung function test increasingly used in small airway diseases. Quality criteria have not yet been globally implemented and time-consuming retrospective overreading is necessary. Little data has been published on children with recurrent wheeze or asthma from multicentered studies.

neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB), a chemoattractant involved in inflammation response.

Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4 T-cells of Atopic Subjects.

Optimal pre-analytical conditions for blood sample processing and isolation of selected cell populations for subsequent transcriptomic and epigenomic studies are required to obtain robust and reproducible results. This pilot study was conducted to investigate the potential effects of timing of CD4 T-cell processing from peripheral blood of atopic and non-atopic adults on their transcriptomic and epigenetic profiles. Two heparinized blood samples were drawn from each of three atopic and three healthy individuals.

IgA memory B-cells are significantly increased in patients with asthma and small airway dysfunction.

Background: Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.

T2-high asthma phenotypes across lifespan.

Rationale: In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.

Objectives: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.

Complete Tracheal Ring Deformity, Recurrent Pneumothoraces and Pleuropulmonary Blastoma in a Child: Coincidence or Common Genetic Cause?

Complete tracheal ring deformity (CTRD) is a rare abnormality of unknown etiology characterized by circumferentially continuous cartilaginous tracheal rings leading to variable degrees of tracheal stenosis with or without additional heart and lung malformations. Pleuropulmonary blastomas (PPB) are rare malignant mesenchymal tumors, which occur almost exclusively in young children. Pathogenic germline variants are associated with PPB but also with other tumors like rhabdomyosarcoma or syndromic diseases like GLOW (Global developmental delay, lung cysts, overgrowth and Wilms tumor) syndrome.

Impact of imposed social isolation and use of face masks on asthma course and mental health in pediatric and adult patients with recurrent wheeze and asthma.

Background: There is currently a dramatic increase in the number of COVID-19 cases worldwide, and further drastic restrictions in our daily life will be necessary to contain this pandemic. The implications of restrictive measures like social-distancing and mouth-nose protection on patients with chronic respiratory diseases have hardly been investigated.

Methods: Our survey, was conducted within the All Age Asthma Cohort (ALLIANCE), a multicenter longitudinal observational study.

Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model.

Background: Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood.

Objective: Our aim was to analyze the role of B cells in a house dust mite (HDM)-based murine asthma model.

Differential expression patterns of glycosphingolipids and C-type lectin receptors on immune cells in absence of functional regulatory T cells.

Background: Glycosylation is a common and complex type of protein posttranslational modification. Altered glycosylation of immunoglobulins in autoimmune diseases has led to the "altered glycan hypothesis" postulating existence of a unique glycan signature on immune cells and extracellular proteins characterized by site-specific relative abundances of individual glycan structures and glycosylation patterns. However, it is not clear how glycosylation on leukocyte subpopulations differ between states of health or inflammation.

FoxP3 deficiency causes no inflammation or neurodegeneration in the murine brain.

Regulatory T cells (Treg) maintain immunological self-tolerance and their functional or numerical deficits are associated with progression of several neurological diseases. We examined the effects of Treg absence on the structure and integrity of the unchallenged murine brain. When compared to control, Treg-deficient FoxP3 mutant mice showed no differences in brain size, myelin amount and oligodendrocyte numbers.

IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma.

IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs.

Absence of Regulatory T Cells Causes Phenotypic and Functional Switch in Murine Peritoneal Macrophages.

Tissue macrophages are important components of tissue homeostasis and inflammatory pathologies. In the peritoneal cavity, resident macrophages interact with a variety of immune cells and can exhibit broad range of phenotypes and functions. Forkhead-box-P3 (FOXP3) regulatory T cells (Tregs) play an indispensable role in maintaining immunological tolerance, yet whether, and how the pathological condition that results from the lack of functional Tregs affects peritoneal macrophages (PM) is largely unknown.

The role of sleep diagnostics and non-invasive ventilation in children with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a degenerative motor neurone disorder causing progressive muscular weakness. Without assisted ventilation or novel therapies, most children with SMA type 1 die before the second year of life due to respiratory failure as the respiratory muscles and bulbar function are severely affected. Active respiratory treatment (mechanically assisted cough, invasive or non-invasive ventilation) has improved survival significantly in recent decades, but often at the cost of becoming ventilator dependent.

Inception of early-life allergen-induced airway hyperresponsiveness is reliant on IL-13CD4 T cells.

Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in children, but the initiating immune mechanisms remain unconfirmed. We demonstrate that both recombinant interleukin-33 (rIL-33) and allergen [house dust mite (HDM) or ] exposure from day 3 of life resulted in significantly increased pulmonary IL-13CD4 T cells, which were indispensable for the development of AHR. In contrast, adult mice had a predominance of pulmonary LinCD45CD90IL-13 type 2 innate lymphoid cells (ILC2s) after administration of rIL-33.

Use of non-invasive ventilation in cerebral palsy.

Patients with cerebral palsy (CP), especially those at the severe end of the spectrum (Gross Motor Function Classification System levels IV-V equivalent), frequently suffer from sleep disturbance and sleep-disordered breathing (SDB). Non-invasive ventilation (NIV) is increasingly used in this patient group, albeit with little published evidence of its effectiveness in CP. This article aims to review the current evidence in the use of NIV in children with CP, highlighting areas of uncertainties, as well as the balance of potential risks, challenges and benefits.

Improved protocol for simultaneous analysis of leukocyte subsets and epithelial cells from murine and human lung.

Purpose: To study and isolate lung cells by flow cytometry, enzymatic digestion and generation of single cell suspensions is required. This significantly influences expression of cellular epitopes and protocols need to be adapted for the best isolation and subsequent analysis of specific cellular subsets.

Materials And Methods: We optimized protocols for the simultaneous isolation and characterization of specific human and murine lung cell types.

Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study.

Background: Acute lower respiratory tract infection is the commonest disease affecting children under five worldwide. Respiratory syncytial virus (RSV) is among the most common causative pathogens. Epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma.

Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33.

Background: The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.

Objective: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.