Objectives

To investigate the association between methylation of transposable elements Alu and long-interspersed nuclear elements (LINE-1) and lung function.

Design

Cohort study.

Setting

Outpatient Veterans Administration facilities in greater Boston, Massachusetts, USA.

Participants

Individuals from the Veterans Administration Normative Aging Study, a longitudinal study of aging in men, evaluated between 1999 and 2007. The majority (97%) were white.

Primary and secondary outcome measures

Primary predictor was methylation, assessed using PCR-pyrosequencing after bisulphite treatment. Primary outcome was lung function as assessed by spirometry, performed according to American Thoracic Society/European Respiratory Society guidelines at the same visit as the blood draws.

Results

In multivariable models adjusted for age, height, body mass index (BMI), pack-years of smoking, current smoking and race, Alu hypomethylation was associated with lower forced expiratory volume in 1 s (FEV1) (β=28 ml per 1% change in Alu methylation, p=0.017) and showed a trend towards association with a lower forced vital capacity (FVC) (β=27 ml, p=0.06) and lower FEV1/FVC (β=0.3%, p=0.058). In multivariable models adjusted for age, height, BMI, pack-years of smoking, current smoking, per cent lymphocytes, race and baseline lung function, LINE-1 hypomethylation was associated with more rapid decline of FEV1 (β=6.9 ml/year per 1% change in LINE-1 methylation, p=0.005) and of FVC (β=9.6 ml/year, p=0.002).

Conclusions

In multiple regression analysis, Alu hypomethylation was associated with lower lung function, and LINE-1 hypomethylation was associated with more rapid lung function decline in a cohort of older and primarily white men from North America. Future studies should aim to replicate these findings and determine if Alu or LINE-1 hypomethylation may be due to specific and modifiable environmental exposures.

Background

Little is known about paternal psychosocial factors and childhood asthma.

Objective

To examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children.

Methods

Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 and again about their child’s asthma at age 3. Fathers were asked about symptoms of post-traumatic stress disorder (PTSD), depression, and anti-social behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood.

Results

After multivariable adjustment, paternal PTSD symptoms, depression, and anti-social behavior were each associated with increased asthma symptoms at age 1 (e.g., OR =1.08 for each 1-point increase in PTSD score, 95% CI=1.03–1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (OR for each 1-point increase in symptoms=1.16, 95% CI=1.00–1.36]). In an analysis combining 1 and 3 year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma.

Conclusions

Both paternal and maternal psychosocial factors may influence asthma morbidity in young Puerto Rican children.

Background

The rise in asthma prevalence over the last few decades may be due changes in pre-natal or early life environment including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern.

Objective

To determine if overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children.

Methods

1376 mother-infant pairs from Project Viva, a longitudinal pre-birth cohort, who had responses for food frequency questionnaires in the 1st and 2nd trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets.

Results

None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or in the multivariable models (multivariable model: OR per one point increase Mediterranean diet 0.98 [95% CI 0.89, 1.08] AHEI-P 1.07 [0.87, 1.30] Prudent 1.02 [0.83, 1.26] Western 0.98 [0.81, 1.19]).

Conclusion

Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants ofoffspring wheeze-associated illness than is dietary pattern.

Background

Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.

Methods

rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.

Results

Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.

Conclusion

Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

The effects of vitamin D on bone metabolism and calcium homeostasis have long been recognized. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. Vitamin D deficiency has been found to be associated with several immune-mediated diseases, susceptibility to infection and cancer. Recently, there has been increasing interest in the possible link between vitamin D and asthma. Further elucidation of the role of vitamin D in lung development and immune system function may hold profound implications for the prevention and treatment of asthma.