Advances in pediatric asthma in 2009: Gaining control of childhood asthma

Szefler, Stanley J.

doi:10.1016/j.jaci.2009.11.006

Cited by 18 publications

(18 citation statements)

References 87 publications

(40 reference statements)

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“…For example, genetic variants of TBX21 have been implicated in childhood asthma, which disproportionally affects African American and Latino children compared with their Caucasian counterparts (Szefler 2010). We found that this gene had different cytosine modification and gene expression levels between the CEU and YRI samples, suggesting that epigenetic variation could be an additional regulatory component for TBX21.…”

Section: Discussionmentioning

confidence: 69%

Genome-Wide Variation of Cytosine Modifications Between European and African Populations and the Implications for Complex Traits

et al. 2013

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Elucidating cytosine modification differences between human populations can enhance our understanding of ethnic specificity in complex traits. In this study, cytosine modification levels in 133 HapMap lymphoblastoid cell lines derived from individuals of European or African ancestry were profiled using the Illumina HumanMethylation450 BeadChip. Approximately 13% of the analyzed CpG sites showed differential modification between the two populations at a false discovery rate of 1%. The CpG sites with greater modification levels in European descent were enriched in the proximal regulatory regions, while those greater in African descent were biased toward gene bodies. More than half of the detected population-specific cytosine modifications could be explained primarily by local genetic variation. In addition, a substantial proportion of local modification quantitative trait loci exhibited population-specific effects, suggesting that genetic epistasis and/or genotype · environment interactions could be common. Distinct correlations were observed between gene expression levels and cytosine modifications in proximal regions and gene bodies, suggesting epigenetic regulation of interindividual expression variation. Furthermore, quantitative trait loci associated with population-specific modifications can be colocalized with expression quantitative trait loci and single nucleotide polymorphisms previously identified for complex traits with known racial disparities. Our findings revealed abundant population-specific cytosine modifications and the underlying genetic basis, as well as the relatively independent contribution of genetic and epigenetic variations to population differences in gene expression. DNA methylation is a covalent cytosine modification that occurs at the C-5 position of cytosines at CpG dinucleotides and is dispersed unevenly over the genome (Bird 2002). Interindividual variation in cytosine modifications can be affected by both the stable underlying genetic sequence and dynamic environmental influences (Flanagan et al. 2006;Bock et al. 2008). Cytosine modifications are known to play an important role in the regulation of gene expression, with promoter methylation acting to silence gene expression (Grewal and Moazed 2003). Previous studies of human variation in gene expression have shown that differential gene expression can influence a variety of complex traits, including susceptibilities to common diseases and variation in drug response (Schadt et al. 2005;Emilsson et al. 2008;Cookson et al. 2009).The lymphoblastoid cell lines (LCLs) from the International HapMap Project (HapMap 2003;HapMap 2005) have been used recently for investigating within-and betweenpopulation differences in promoter methylation (Bell et al. 2011;Fraser et al. 2012). Furthermore, previous work from our group and others has demonstrated that common genetic variants and microRNAs contributed to the variation in gene expression between LCLs derived from individuals of We reasoned that an evaluation of the natural variation ...

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Section: Discussionmentioning

confidence: 69%

Genome-Wide Variation of Cytosine Modifications Between European and African Populations and the Implications for Complex Traits

et al. 2013

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“…Montelukast has been shown in numerous clinical trials to effectively control EIB in children. A placebo-controlled, double-blinded, randomized two-period crossover study 58 was conducted in 27 children who had a mean baseline FEV 1 of 87% of predicted values and a maximal fall in FEV 1 of 35% after exercising on a treadmill for 6 min. None of the children was taking any controller medication for asthma.…”

Section: Efficacy and Clinical Trialsmentioning

confidence: 99%

“…58 Montelukast is unlikely to retard growth and is thus a viable alternative, provided acceptable control of asthma symptoms is achieved. Montelukast may be preferred in those instances where very young children are unable to operate inhaler devices efficiently and parents have the option of an easy-to-administer oral preparation such as montelukast without resorting to systemic corticosteroids.…”

Section: Patient Preferencementioning

confidence: 99%

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Montelukast Sodium: Administration to Children to Control Intermittent Asthma

2010

Clinical Medicine Reviews in Therapeutics

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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the chemotherapy of exercise-induced asthma. It has also been used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma because most exacerbations of this condition involve respiratory virus infection-triggered inflammatory mechanisms which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this review is to evaluate the role of montelukast in the treatment of intermittent asthma in children.

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“…[1][2][3] Inpatient (IP) hospitalizations are one potential result of an exacerbation of asthma, which is a chronic inflammatory condition of the airways. Exacerbations also may lead to missed days of school and work for the child and parent, impaired daily functions and quality of life, emergency department (ED) visits, or death.…”

Section: Introductionmentioning

confidence: 99%