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The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges

In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the "microbial hypothesis" and the "farm effect"; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures.

Time spent outdoors through childhood and adolescence - assessed by 25-hydroxyvitamin D concentration - and risk of myopia at 20 years

To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25-hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6-, 14-, 17- and 20-year follow-ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent -0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age-specific 25(OH)D concentrations. Linear mixed-effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years.

LPS binding protein and activation signatures are upregulated during asthma exacerbations in children

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children during acute virus-associated exacerbations and later during convalescence.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell recruitment and perturbation of regulatory T cell expansion in the lungs.

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group.

Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 years

Human perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood.

Vitamin D deficiency linked to childhood asthma

Researchers at The Kids Research Institute Australia have found children with vitamin D deficiency are more likely to develop asthma.

Interaction between adaptive and innate immune pathways in the pathogenesis of atopic asthma: Operation of a lung/bone marrow axis

Atopic asthma is the most common form of asthma, particularly during childhood, and in many cases it persists into adult life.