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Background: Pollen exposure is associated with respiratory symptoms in children and adults. However, the association of pollen exposure with respiratory symptoms during infancy, a particularly vulnerable period, remains unclear. We examined whether pollen exposure is associated with respiratory symptoms in infants and whether maternal atopy, infant's sex or air pollution modifies this association. Methods: We investigated 14,874 observations from 401 healthy infants of a prospective birth cohort. The association between pollen exposure and respiratory symptoms, assessed in weekly telephone interviews, was evaluated using generalized additive mixed models (GAMMs). Effect modification by maternal atopy, infant's sex, and air pollution (NO2, PM2.5) was assessed with interaction terms. Results: Per infant, 37 ± 2 (mean ± SD) respiratory symptom scores were assessed during the analysis period (January through September). Pollen exposure was associated with increased respiratory symptoms during the daytime (RR [95% CI] per 10% pollen/m3: combined 1.006 [1.002, 1.009]; tree 1.005 [1.002, 1.008]; grass 1.009 [1.000, 1.23]) and nighttime (combined 1.003 [0.999, 1.007]; tree 1.003 [0.999, 1.007]; grass 1.014 [1.004, 1.024]). While there was no effect modification by maternal atopy and infant's sex, a complex crossover interaction between combined pollen and PM2.5 was found (p‐value 0.003). Conclusion: Even as early as during the first year of life, pollen exposure was associated with an increased risk of respiratory symptoms, independent of maternal atopy and infant's sex. Because infancy is a particularly vulnerable period for lung development, the identified adverse effect of pollen exposure may be relevant for the evolvement of chronic childhood asthma. [ABSTRACT FROM AUTHOR]

Background: Current in vitro allergen‐specific IgE (sIgE) detection assays measure IgE against allergen extracts or molecules in a single‐ or multiplex approach. Direct comparisons of the performance of such assays among young children with common presentations of allergic diseases regardless of sensitization status are largely missing. Objectives: The aim of this study was a comparison of the analytical and diagnostic performance for common clinical questions of three commonly used technologies which rely upon different laboratory methodologies among children of the All Age Asthma (ALLIANCE) cohort (clinicaltrials.gov: NCT02496468). Methods: Sera from 106 paediatric study participants (mean age 4 years) were assessed for the presence of sIgE by means of the ImmunoCAP™ sx1 and fx5 mixes, the ImmunoCAP ISAC™ 112 microarray and a Euroline™ panel. Results: Total and negative concordance was high (>82%–>89%), while positive concordance varied considerably (0%–100%) but was also >50% for the most common sensitizations analysed (house dust mite and birch). All three test systems showed good sensitivity and specificity (AUC consistently > 0.7). However, no significant differences with regard to identifying sIgE sensitizations associated with symptoms in children with suspected pollen‐ or dust‐triggered wheeze or presenting with symptoms of allergic rhinoconjunctivitis or food allergy were detected. Extending the number of allergens did not change the similar performance of the three assay systems. Conclusion and Clinical Relevance: Among young children, the three sIgE assays showed good analytical and diagnostic concordance. Our results caution that the identification of larger numbers of sensitizations by more comprehensive multiplex approaches may not improve the clinical utility of sIgE testing in this age group. [ABSTRACT FROM AUTHOR]

Background: Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire‐based studies by self‐report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6‐year‐old children. Methods: Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results: Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35‐7.07) and 3.16 (1.43‐6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion: These results underline the importance of prevention and remediation efforts of moisture and mold‐damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development. [ABSTRACT FROM AUTHOR]

Human rhinovirus infection (HRVI) plays an important role in asthma exacerbations and is thought to be involved in asthma development during early childhood. We hypothesized that HRVI causes differential DNA methylation and subsequently differential mRNA expression in epithelial cells of children with asthma. Primary nasal epithelial cells from children with (n = 10) and without (n = 10) asthma were cultivated up to passage two and infected with Rhinovirus-16 (RV-16). HRVI-induced genome-wide differences of DNA methylation in asthmatics (vs. controls) and resulting mRNA expression were analyzed by the HumanMethylation450 BeadChip Kit (Illumina) and RNA sequencing. These results were further verified by pyrosequencing and quantitative PCR, respectively. 471 CpGs belonging to 268 genes were identified to have HRVI-induced asthma-specifically modified DNA methylation and mRNA expression. A minimum-change criteria was applied to restrict assessment of genes with changes in DNA methylation and mRNA expression of at least 3% and least 0.1 reads/kb per million mapped reads, respectively. Using this approach we identified 16 CpGs, including HLA-B-associated transcript 3 (BAT3) and Neuraminidase 1 (NEU1), involved in host immune response against HRVI. HRVI in nasal epithelial cells leads to specific modifications of DNA methylation with altered mRNA expression in children with asthma. The HRVI-induced alterations in DNA methylation occurred in genes involved in the host immune response against viral infections and asthma pathogenesis. The findings of our pilot study may partially explain how HRVI contribute to the persistence and progression of asthma, and aid to identify possible new therapeutic targets. The promising findings of this pilot study would benefit from replication in a larger cohort. [ABSTRACT FROM AUTHOR]

Summary: Bacterial and viral infections occur early and recurrently in life and thereby impose a substantial disease burden. Besides causing clinical symptoms, a potential role of infection in the development of the asthma syndrome later in life has also been suggested. However, whether bacterial and viral infections unmask host factors in children at risk of asthma or whether they directly cause asthma remains unclear; both viewpoints could be justified, but the underlying mechanisms are complex and poorly understood. Recently, the role of the bacterial microbiome has been emphasised. But data are still sparse and future studies are needed for definitive conclusions to be made. In this Review, we discuss present knowledge of viruses and bacteria that infect and colonise the respiratory tract and mucosal surfaces, including their timepoint of action, host factors related to infection, and their effect on childhood asthma. Childhood asthma could be the result of a combination of altered host susceptibility and infectious agents. [ABSTRACT FROM AUTHOR]

Background: Asthma and wheezing disorders in childhood and adulthood are clinically heterogeneous regarding disease presentation, natural course, and response to treatment. Deciphering common disease mechanisms in distinct subgroups requires harmonized molecular (endo-) phenotyping of both children and adult patients with asthma in a prospective, longitudinal setting.Methods: The ALL Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL) is a prospective, multi-center, observational cohort study with seven recruiting sites across Germany. Data are derived from four sources: (a) patient history from medical records, (b) standardized questionnaires and structured interviews, (c) telephone interviews, and (d) objective measurements. Objective measurements include amongst others lung function and quantitative assessment of airway inflammation and exhaled breath, peripheral blood, skin, nasal, pharyngeal, and nasopharyngeal swabs, nasal secretions, primary nasal epithelial cells, and induced sputum. In cases, objective measurements and biomaterial collection are performed regularly, while control subjects are only examined once at baseline.Discussion: The standardized and detailed collection of epidemiological and physiological data, and the molecular deep phenotyping of a comprehensive range of biomaterials in a considerable number of study participants across all ages are the outstanding characteristics of this multi-center cohort. Despite extensive biomaterial sampling, and a recruitment strategy that also includes pre-school children as young as 6 months, attrition is low. In children 83.9%, and in adults 90.5% attended the 12-month follow-up. The earliest time-point to include cases, however, is disease manifestation. Therefore, unraveling mechanisms that drive disease onset is limited, as this question can only be answered in a population-based birth cohort. Nonetheless, ALLIANCE offers a unique, integrative and inter-disciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood. Ultimately, this approach aims to translate its most significant findings into clinical practice, and to improve asthma transition from adolescence to adulthood.Trial Registration: NCT02496468 for pediatric arm, NCT02419274 for adult arm. [ABSTRACT FROM AUTHOR]