Genetic characterization of preschool wheeze phenotypes.

Rationale: Preschool wheeze is a heterogenous and poorly understood clinical syndrome. As a result, current treatments are insufficient, and prevention is not possible.

Objectives: To increase understanding of the genetic susceptibility and underlying disease mechanisms of wheeze phenotypes in early childhood through large-scale genome-wide association study (GWAS) analyses.

Exploring geographic differences in IgE response through network and manifold analyses.

Background: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences.

Objective: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally.

Patterns of Respiratory Symptoms and Asthma Diagnosis in School-Age Children: Three Birth Cohorts.

Background: Many studies used information on wheeze presence/absence to determine asthma-related phenotypes. We investigated whether clinically intuitive asthma subtypes can be identified by applying data-driven semi-supervised techniques to information on frequency and triggers of different respiratory symptoms.

Methods: Partitioning Around Medoids clustering was applied to data on multiple symptoms and their triggers in school-age children from three birth cohorts: MAAS (n = 947, age 8 years), SEATON (n = 763, age 10) and ASHFORD (n = 584, age 8).

Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies.

Background: Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology.

Methods: We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors.

From Peptide to Protein: Development of Conversion Factors for the Quantification of Gluten Using Targeted Mass Spectrometry.

Immuno- and mass spectrometry (MS) test methods have been used to ensure "gluten-free" food products contain less than 20 ppm of gluten. However, comparison of test method performance is difficult due to differences in reporting units. A set of wheat flour fractions was prepared and characterized regarding immunoglobulin E (IgE)-reactivity and protein profile, which were then used to screen a panel of gluten peptides to identify reporters suitable for use in an MS test method for gluten determination.

The impact of dosage timing for inhaled corticosteroids in asthma: a randomised three-way crossover trial.

Background: Asthma demonstrates a robust daily rhythm, with airflow obstruction and airway inflammation peaking overnight. Aligning the timing of drug administration with rhythms in disease (chronotherapy) may improve therapeutic efficacy. We aimed to evaluate the impact of dosage timing for inhaled corticosteroids in asthma.

Circulating CC16, immune response to Mycoplasma pneumoniae and lung function: a population-based, multi-cohort study.

Background: Sufficient levels of club cell secretory protein (CC16) are essential to protect against lung function impairments. Experimental studies have demonstrated that CC16 modulates inflammatory responses and protects against airway hyperresponsiveness following Mycoplasma pneumoniae (Mp) infection. Individuals with asthma have low CC16 levels and increased susceptibility to Mp infection.

Exploring the temporal interplay of allergic sensitization and asthma via graph and manifold analysis.

Background: The association between allergic sensitization and asthma is well-documented, but its precise role in asthma remains uncertain. Component-resolved diagnostics allows detailed assessment of IgE-sensitization to multiple allergenic molecules (c-sIgE). We applied advanced network embedding techniques to investigate the dynamics of temporal development of multiple c-sIgE and identify networks associated with asthma.

Trajectories of airflow limitation from childhood to early adulthood: an analysis of six population-based birth cohorts.

Background: Lung function during childhood is an important predictor of subsequent health and disease. Understanding patterns of lung function and development of airflow limitation through childhood is necessary to inform lung function trajectories in relation to health and chronic airway disease. We aimed to derive trajectories of airflow limitation from childhood (age 5-8 years) into early adulthood (age 20-26 years) using repeated spirometry data from birth cohorts.

Childhood lung function is associated with adolescent-onset and persistent asthma.

Background: Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. The aims of the present study were to investigate the association between childhood lung function and onset and persistence of asthma during adolescence.

Methods: In the population-based BAMSE (Sweden), PIAMA (Netherlands) and MAAS (UK) birth cohorts, we analysed the association of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC and forced expiratory volume at 75% of FVC at age 8 years with asthma onset and persistence in adolescence (age 12-16 years) using cohort-specific logistic regression analysis followed by meta-analysis.

Association of urinary eosinophilic protein X at age 3 years and subsequent persistence of wheezing and asthma diagnosis in adolescence.

Background: Wheezing is common in early life, but most children stop wheezing by school age. However, the prediction of course of wheezing through childhood is difficult.

Objective: To investigate whether urinary EPX (a marker of eosinophil activation) in children at age 3 years may be useful for the prediction of wheeze persistence and future asthma diagnosis.

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests.

Introduction: The diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend including confirmation of variable airflow obstruction. Some recommend using a sequence of objective tests; however the tests used, the specific cut-off values and the specified order are yet to be validated.

Asthma diagnosis: a comparison of established diagnostic guidelines in adults with respiratory symptoms.

Background: Considerable variability exists between asthma diagnostic guidelines. We tested the performance characteristics of the European Respiratory Society (ERS), the National Institute for Health and Care Excellence (NICE) and the Global Initiative for Asthma (GINA) guidelines for the diagnosis of asthma in adults.

Methods: In this prospective observational study (ISRCTN-11676160, May 2019-June 2022), participants referred from primary care with clinician-suspected asthma underwent comprehensive investigation including: spirometry, bronchodilator reversibility, fractional exhaled nitric oxide, peak expiratory flow variability, bronchial challenge testing with methacholine and mannitol, and responsiveness to inhaled corticosteroid therapy.

The impact of time of day on the diagnostic performance of tests for asthma.

https://bit.ly/4b79e5J.

Trajectories of egg sensitization in childhood: Two birth cohorts in Asia and Europe.

Background: Hen's egg exposure through impaired skin barrier is considered a major mechanism of sensitization to eggs. However, the impact of filaggrin (FLG) gene loss-of-function mutations on the natural history of egg sensitization lacks consensus among studies.

Objective: To evaluate the association between the natural course of egg sensitization and FLG mutations.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

Rationale: Lung function in early adulthood is associated with subsequent adverse health outcomes.

Objectives: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.

Methods: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC).

Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses.

Background: Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheeze. There are few mechanistic data linking chromosome 17q12-q21 to wheezing illness.

Objective: We investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus.

Component-specific clusters for diagnosis and prediction of allergic airway diseases.

Background: Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes.

Objective: To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms.

Obstructive and restrictive spirometry from school age to adulthood: three birth cohort studies.

Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood.

Methods: In this study, we analysed pooled data from three UK population-based birth cohorts established between 1989 and 1995.