Augusto Litonjua

..The purpose of this review is to update the last review in this journal and examine the evidence of the relationship between vitamin D deficiency and childhood asthma and allergies...

..Ongoing clinical trials will help determine whether results of observational studies can be applied to the clinical setting...

..A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results...

..We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics...

..Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization...

..Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene...

..Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis...

..We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects...

..The gene that encodes the beta2-adrenergic receptor (ADRB2) is one of the most studied candidate genes in asthma. This review examines recent articles of the relationship between ADRB2 polymorphisms and asthma...

..However, a substantial proportion of patients with asthma do not have a favorable response to these drugs, and identifying genetic determinants of drug response may aid in tailoring treatment for individual patients...

..It has been postulated that vitamin D deficiency may explain a portion of the asthma epidemic. The purpose of this review is to present the evidence for a role of vitamin D in asthma...

..Low intakes of dietary antioxidants may contribute to increases in asthma and allergy...

..To investigate the relationship of common single nucleotide polymorphisms (SNPs) of the beta(2)-adrenergic receptor (AR) gene at codons 16 and 27, and the intermediate phenotype of airways hyperresponsiveness...

..Providing adequate vitamin D supplementation in pregnancy may lead to significant decreases in asthma incidence in young children...

..5, 11.7, respectively, for the children. We conclude that a large proportion of the racial/ethnic differences in asthma prevalence in our study is explained by factors related to income, area of residence, and level of education...

..It is likely that nutrients may exert their strongest effect early in life, when both the immune system and the lungs are not yet fully developed...

..The relationship between body mass index (BMI) and the development of an objective marker for asthma, methacholine airway hyperresponsiveness (AHR), was investigated in adult men...

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..To confirm these findings, we tested the hypothesis that serum cytokines are associated with longitudinal lung function decline...

..03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs...

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..Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control...

..The Met772-AC9 polymorphism represents one of most likely several multi-gene polymorphisms along the receptor-relaxation axis, which together may provide for a composite pharmacogenetic index for asthma therapy...

..Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood...

..Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups...

..To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR)...

..4 x 10(-4). IREB2 protein and mRNA were increased in lung-tissue samples from COPD subjects in comparison to controls. In summary, gene-expression and genetic-association results have implicated IREB2 as a COPD susceptibility gene...

..To investigate the relationship between current and early life factors and airway responsiveness to inhaled methacholine in children with a median age of 7.0 years...

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..The association of particulate matter (PM) with cardiovascular morbidity and mortality is well documented. PM-induced ischemia is considered a potential mechanism linking PM to adverse cardiovascular outcomes...

..Lead accumulates in the vasculature and is associated with vascular oxidative stress, which can promote functional and structural vascular disease...

..The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood...

..Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown...

..Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels...

..We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in asthma...

..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...

..2 x 10(-11), combined odds ratio in case-control studies 0.76, 95% confidence interval 0.69-0.83)...

..We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter...

..Little is known regarding the role of genetic variation surrounding T-bet in the development of human AHR...

..We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke...

..Two common nonsynonymous SNPs did not demonstrate significant associations in either a family-based or case-control analysis. Exonic SNPs in the elastin gene do not appear to be common risk factors for severe COPD...

..Fine particulate matter [aerodynamic diameter </= 2.5 mum (PM(2.5))] has been associated with autonomic dysregulation...

..We previously identified single nucleotide polymorphisms in the arginase 1 (ARG1) gene, which are associated with β₂-agonist bronchodilator response (BDR)...

..We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts...

..We hypothesized that exposure to environmental fungi may modulate the effect of chitinases in individuals with asthma...

..Additional pharmacogenetic investigations into regions of chromosomal diversity, including copy number variation and inversions, are warranted...

..Vitamin D status might play a role in preventing asthma exacerbations...

..Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q...

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..We sought to relate candidate gene SNP data with bronchodilator response and measure the predictive accuracy of a model constructed with genetic variants...

..To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma, based independently on lung function changes or asthma exacerbations...

..Few prospective data link early childhood adiposity with asthma-related symptoms...

..The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies...

..Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma...

..The purpose of this work was to examine the relation between cytokine secretions by cord blood mononuclear cells and acute lower respiratory illness in a birth cohort of 297 children...

..Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma...

..The implications of these findings for future development of allergy or asthma are, as yet, unknown...

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..We examined whether bottle feeding in the bed or crib before sleep time in the first year of life is associated with wheezing in the first 5 years of life...

..Further investigation may contribute to our understanding of the mechanisms through which particulates may increase respiratory and cardiac morbidity among vulnerable populations...

..We hypothesize that genetic variants in or near the TGFB1 gene influence the pathogenesis of COPD among cigarette smokers...

..There was no association between wheezing and exposure to dog or dog allergen, and the father's allergy status had no effect on the relation between childhood wheezing and cat exposure...

..07). Despite the reduced support for linkage upon further analysis, it remains possible that chromosome 8p contains a gene that influences COPD susceptibility. There is marginal, though not convincing, evidence for association with MSR1...

..Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations...

..Ozone has heterogeneous effects on lung function. We investigated whether obesity and airways hyperresponsiveness (AHR) modify the acute effects of ozone on lung function in the elderly...

..However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear...

..It has been hypothesized that day care--related infections may explain the inverse relation between day care attendance in early life and asthma in childhood...

..Decreased lung function has been linked to increased inflammation and oxidative stress. Statins have demonstrated antiinflammatory and antioxidant properties...

..4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood...

..There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age...

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..Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic...

..Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown...

..In this manuscript, we discuss these considerations and provide concrete examples with GWAS data for an asthma clinical trial using parent-offspring trios...

..Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known...

..A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility...

..01 to 1.12; P=0.03). The baseline serum uric acid level is a durable marker of risk for the development of hypertension. The association is independent of elements of the metabolic syndrome, alcohol intake, and renal function...

..Positive skin tests to allergens derived from mouse urine have been reported among patients with asthma. Very few data are available detailing the titer of IgE Ab to mouse allergen and how it varies by location and population...

..Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children...

..These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases...

..Current smoking was uniformly associated with decreased cytokine levels. CONCLUSION: IFN-gamma, GM-CSF, and other cytokines may be useful serum markers in population studies of airway responsiveness...

..These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD...

..A more complete understanding of the molecular mechanism awaits identification of the functional effect of the polymorphism...

..End of Abstract) ..

..Additionally, supplementation with vitamin D can be implemented in cost-effective population-based programs to prevent the development of, and treat these disorders. ..

..The results of this proposal will shed light on potential mechanisms that affect lung function decline in aging. ..

..Blood for genetic material is currently being collected on the two cohorts, and endotoxin will be measured from stored, frozen house dust. ..