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Rationale-Premorbid infant lung function predicts childhood wheeze, but it is unclear whether lower infant lung function is most closely associated with atopic or non-atopic preschool wheeze.Objective-To examine the association between premorbid infant lung function and preschool wheeze according to atopic or non-atopic wheeze phenotype. Additionally, to explore the relations of ADAM33 polymorphism with lung function during infancy, preschool wheeze and atopy.Methods-Infant lung function was measured in147 healthy term infants aged 5-14 weeks. Raised volume rapid thoracoabdominal compression was performed to determine FEV 0.4 . Atopic status was determined by skin prick testing at 3 years and wheeze ascertained from parental questionnaires (1 and 3 years). ADAM33 polymorphisms were examined using haplotype analysis.Measurements and Main Results-Early infancy V'max FRC and FEV 0.4 were lower in those who wheezed in the first year (p=0.002 and p=0.03), and lower V'max FRC was associated with wheeze in the third year (p=0.006). Non-atopic children who wheezed in their third year of life had lower FEV 0.4 , compared to non-atopic children who did not wheeze (p=0.02), whilst atopic children with wheeze did not (p=0.4). No ADAM33 haplotype was associated with infant lung function, preschool wheeze or atopy after correction for multiple testing. KCP does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. MJR-Z does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. ECO does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. HMI does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. KMG does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. SRC does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.GCR does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. JBC does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. JWH does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. JSL does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.This article has an online data supplement, which is accessible from this issue's Conclusions-Lower premorbid infant lung function was present in infants who subsequently wheezed during the first and third years of life. Lower FEV 0.4 was associated with non-atopic wheeze but not atopic wheeze at 3 years of age. The relation between ADAM33 polymorphism, infant lung function and preschool wheeze requires examination in larger studies.

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Emerging evidence suggests trauma experienced in childhood has negative transgenerational implications on offspring mental and physical health. The objective was to investigate whether early life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included three generations of Swedish families with a base population of 453 516 children (G3) born 2001-2012. Exposure was defined as the middle generation (G2) experiencing bereavement in childhood due to death of a parent (G1). Outcomes in G3 included two diagnoses of inflammatory diseases including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways including investigation of mediation by G2 mood disorders and socioeconomic status. Results found that early-life bereavement experienced by women was associated with early-onset offspring asthma (Hazard Ratio (HR) 1.15, 95%CI: 1.08,1.28) and mediation analysis revealed that 28-33% of the association may be mediated by socioeconomic status and 9-20% by mood disorders. Early-life bereavement experienced by men was associated with auto-immune diseases in offspring (HR 1.31, 95%CI 1.06,1.61) with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk for inflammatory diseases which is in part mediated by mood disorders and SES.