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Background Several CD14 gene-environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect. Methods CD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, β(1,3)-glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure ( TSE; questionnaire data) at 2 and 10 yr were explored. Results Children in homes without pets had larger increases in CD14 methylation through childhood (2-10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school-age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037). Conclusion Pet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments. [ABSTRACT FROM AUTHOR]

Early intervention with inhaled corticosteroid (ICS) treatment for lung function development in childhood is debated. In view of lung function at birth, we aimed to assess if early use of ICS influenced lung function at 10 yrs of age. A 10-yr follow-up study of 614/802 children (mean age 10.9 ± 0.9 yrs) with lung function measurements at birth in the Environment and Childhood Asthma study in Oslo included information on ICS treatment (124 with history of asthma) obtained at 2 and 10 yrs by parental interviews. Main outcomes at 10 yrs were the best values (% predicted and Z-scores) of forced expiratory volume in 1 s (FEV1) and mid-expiratory flow. The main explanatory factors were never, past or current use of ICS and Z-scores of the tidal flow-volume ratio tPTEF/tE [time to peak expiratory flow (tPTEF) and total expiratory time (tE)] at birth. ICS treatment, reported by 11.9% of children in the population sample and 71.6% with current asthma, did not significantly influence lung function from birth to 10 yrs. The best values (and Z-scores) of FEV1, and mid-expiratory flow were similar (p > 0.1) in subjects receiving ICS during and after 0-3 yrs of age, after 3 yrs only or currently compared with steroid naïve children. Almost half of the change in lung function 0-10 yrs was explained by gender, a history of asthma and tPTEF/tE at birth. ICS treatment for asthma, reported in every eighth child by age 10 yrs, did not significantly improve lung function from birth to 10 yrs. [ABSTRACT FROM AUTHOR]

The causal relationship between lower respiratory tract infections (LRIs) in early life and reduced lung function later in childhood is unsettled. Therefore, we assessed whether LRIs the first 2 yr of life influenced lung function development from birth to school age. In the prospective Oslo birth cohort, ‘the Environment and Childhood Asthma (ECA) study’ lung function was measured at birth in 802 infants by tidal flow volume loops and in 664 infants by passive respiratory mechanics and half yearly questionnaires, including LRI questions, were completed until 2 yr of age. The present study includes 607 children with information about LRIs the first 2 yr of life and successfully forced expiratory flow (FEF) volume measurements at the 10-yr follow-up assessment. At 10 yr of age, FEF at 50% of forced vital capacity (FEF50) (mean 95% confidence interval) was reduced in children with at least one bronchiolitis (85.0, 80.6–89.5, p = 0.020) or bronchitis (86.2, 82.6–89.8, p = 0.030) or ≥3 LRIs (83.4, 78.1–88.8, p = 0.017) when compared with no LRIs (90.6, 88.8–92.5) by 2 yr of life. The effects were significant in girls only when stratifying for gender. Among girls with later bronchiolitis compliance of the respiratory system (3.64, 3.17–4.10 vs. 4.18, 3.98–4.37, p = 0.031) and the ratio of time to peak tidal expiratory flow to total expiratory time ( tPTEF/ tE) measured at birth was significantly reduced (0. 26, 0.23–0.29 vs. 0.32, 0.30–0.33, p = 0.005) when compared with children with no LRIs. Change in lung function from birth (by tPTEF/ tE) to 10 yr of age was not significantly associated with LRIs the first 2 yr of life, and LRIs by 2 yr of life were not significantly associated with lung function at 10 yr of age in regression analyses including lung function at birth and other possible predictors of lung function at 10 yr. In our study, LRIs during the first 2 yr of life did not impair lung function development from birth until 10 yr of age. [ABSTRACT FROM AUTHOR]