Associations of pre- and postnatal exposures with optic nerve status in young adults.

PURPOSE: We aimed to explore the effect of multiple pre- and postnatal exposures on optic nerve status in young adults due to this critical period for development. METHODS: We analysed peripapillary retinal nerve fibre layer (RNFL) status and macular thickness at age 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000 ) cohort in relation to several exposures. RESULTS: Of the 269 participants (median (IQR) age, 17.6 (0.6) years; 124 boys), 60 participants whose mothers had smoked during pregnancy had a thinner RNFL: adjusted mean difference -4.6 µm (95% CI -7.7; -1.5 µm, p = 0.004) compared with participants whose mothers had not smoked during pregnancy. A total of 30 participants who were exposed to tobacco smoke both during foetal life and childhood had thinner RNFL: -9.6 µm (-13.4; -5.8 µm, p < 0.001). Smoking during pregnancy was also associated with a macular thickness deficit: -4.7 µm (-9.0; -0.4 µm, p = 0.03). Higher indoor concentrations of particulate matter 2.5 (PM2.5) was associated with thinner RNFL: -3.6 µm (-5.6; -1.6 µm, p < 0.001) and a macular deficit: -2.7 µm (-5.3; -0.1 µm, p = 0.04) in the crude analyses, but not in the adjusted analyses. No difference was found among participants who smoked at age 18 years compared with non-smokers on RNFL or macular thickness. CONCLUSIONS: We found that exposure to smoking during early life was associated with a thinner RNFL and macula at age 18 years. The absence of an association between active smoking at 18 years suggests that the vulnerability of the optic nerve is highest during prenatal life and early childhood.

Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB.

BACKGROUND: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate. OBJECTIVE: We sought to identify genetic interaction associated with the development of childhood asthma. METHODS: We performed an exhaustive search for pairwise interaction between genetic single nucleotide polymorphisms using 1204 cases of a specific phenotype of early childhood asthma with severe exacerbations in patients aged 2 to 6 years combined with 5328 nonasthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts. RESULTS: We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype, and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation. CONCLUSIONS: We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.