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.

Continuous Rather Than Solely Early Farm Exposure Protects From Hay Fever Development.

Background: An important window of opportunity for early-life exposures has been proposed for the development of atopic eczema and asthma.

Objective: However, it is unknown whether hay fever with a peak incidence around late school age to adolescence is similarly determined very early in life.

Methods: In the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort potentially relevant exposures such as farm milk consumption and exposure to animal sheds were assessed at multiple time points from infancy to age 10.

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.

The rising of old foes: impact of lockdown periods on "non-SARS-CoV-2" viral respiratory and gastrointestinal infections.

Background: During COVID-19-related public health non-pharmaceutical prevention measures, such as social distancing, lockdown periods and use of face masks, a decrease in viral respiratory and gastroenterological infections was observed worldwide. Following discontinuation of preventative measures, a potential increase of respective infections outside of their usual seasons was a matter of concern.

Method: We aimed to illustrate annual distribution of confirmed viral infections between 2017 and 2021 based on 32,506 clinical samples in a German pediatric tertiary care center and to explore the impact of the COVID-19 pandemic on the epidemiology of these infections in children.

Immune Responsiveness to LPS Determines Risk of Childhood Wheeze and Asthma in 17q21 Risk Allele Carriers.

In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in  = 445 children.

Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life.

Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood.

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking.

Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases.

IL-33 polymorphisms are associated with increased risk of hay fever and reduced regulatory T cells in a birth cohort.

Background: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis.

A switch in regulatory T cells through farm exposure during immune maturation in childhood.

Background: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs).

Asthma and the hygiene hypothesis. Does cleanliness matter?

Rationale: The early hygiene hypothesis explained the development of allergies by a lack of infections; nowadays, the aspect of excessive cleanliness in affluent populations seems to have replaced this concept. Yet, no investigation has shown that home or personal cleanliness relate to allergic diseases.

Objectives: To relate personal and home cleanliness to risk of asthma and allergies.

Parental hay fever reinforces IgE to pollen as pre-clinical biomarker of hay fever in childhood.

Background: An early IgE response to grass or birch pollen can anticipate seasonal allergic rhinitis to pollen later in life or remain clinically silent.

Objective: To identify risk factors early in life that allow discriminating pathogenic from non-pathogenic IgE responses and contribute to the development of seasonal allergic rhinitis to grass pollen.

Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990.

Perinatal influences on the development of asthma and atopy in childhood.

Background: In most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained.

Objective: To examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.

Regulation of TH17 markers early in life through maternal farm exposure.

Background: Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by TH1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as TH17 cells, influenced by genetic predisposition.

Objective: We examined the role of maternal farm exposure and genetic predisposition on TH17 cell responses to innate and adaptive immune stimulation in cord blood.

LUNOKID: can numerical American Thoracic Society/European Respiratory Society quality criteria replace visual inspection of spirometry?

The gold standard for assessing quality of forced expiratory manoeuvres is visual inspection by an expert. American Thoracic Society/European Respiratory Society numerical quality criteria (NQC) include back-extrapolated volume (BEV), repeatability and forced expiratory time (FET). Equipment currently available provides feedback tempting the investigator to use NQC as pass-fail criterion.

STAT6 polymorphisms are associated with neonatal regulatory T cells and cytokines and atopic diseases at 3 years.

Background: The transcription factor STAT6 is crucial for activation of the interleukin (IL)-4/IL-13 pathway and has been linked to regulatory T cells (Tregs). Associations of STAT6 polymorphisms with IgE levels were described; however, their impact on neonatal immune responses and early disease development is unknown.

Methods: STAT6 polymorphisms were genotyped in cord blood mononuclear cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies.

Background: Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect.

Methods: In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I).

[New spirometric reference values for children and adolescents in Germany considering height and non-linear age effects: the LUNOKID-study].

Background: Comparing children's lung function with reference values is important for diagnosing respiratory diseases. The values by Zapletal et al., commonly used nowadays, are not appropriate for the current stage of children's development.