Further studies are urgently needed in order to identify effective and sustainable strategies for reducing the dramatic health disparities experienced by disadvantaged, urban, and minority youth with asthma. Vitamin D deficiency is more common among African American (AA) individuals, especially those from urban environments or with obesity. We and others have contributed to increasing evidence that vitamin D insufficiency may contribute to more severe asthma through increased risk of respiratory infection and decreased glucocorticoid sensitivity. Indeed, low vitamin D levels were recently linked with the need for exogenous glucocorticoids and increased asthma severity. Particularly relevant to health disparities, we showed a strong association between vitamin D insufficiency and asthma in urban African American (AA) youth. Because AA youth residing in urban Washington, DC have markedly worse asthma than other racial/ethnic groups (e.g. prevalence rate 20% higher than the national rate 15 and emergency department utilization rates up to 5 times the national rates and nearly 10 times the Healthy People 2010 target rate), we will utilize our access to this population at the extreme of asthma disparities to examine the contribution of vitamin D to disparities in the chronic control and acute severity of asthma. The overall goal of this application is to provide critical epidemiological/molecular information that will inform the interpretation of ongoing and impending randomized clinical trials of vitamin D supplementation in asthma, especially with regard to urban AA youth with asthma. The knowledge generated by the experiments in this application will be crucial to translation of this inexpensive, easily-accessible potential therapy for asthma. We hypothesize that low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with poor chronic asthma control, worse acute asthma severity, and glucocorticoid insensitivity.
AIM 1. Define asthma phenotypic clusters and determine cross- sectional inter- and intra-cluster associations with serum 25(OH)D levels within and between AA and non-AA youth.
AIM 2. Determine prospective associations among serum 25(OH)D levels and: (a) chronic asthma control and (b) acute asthma severity within and between AA and non-AA youth.
AIM 3. Show the effect of vitamin D on glucorticoid regulation of inflammatory mediators in asthmatic airway epithelial cells.
The overall goal of this application is to provide critical epidemiological/molecular information that will inform the interpretation of ongoing and impending randomized clinical trials of vitamin D supplementation in asthma, especially with regard to urban AA youth with asthma. The knowledge generated by the experiments in this application will be crucial to translation of this inexpensive, easily-accessible potential therapy for asthma.
|Pérez-Losada, Marcos; Authelet, Kayla J; Hoptay, Claire E et al. (2018) Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas. Microbiome 6:179|
|Bartel, Sabine; Schulz, Nikola; Alessandrini, Francesca et al. (2017) Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma. Sci Rep 7:46026|
|Pérez-Losada, Marcos; Alamri, Lamia; Crandall, Keith A et al. (2017) Nasopharyngeal Microbiome Diversity Changes over Time in Children with Asthma. PLoS One 12:e0170543|
|Pérez-Losada, Marcos; Crandall, Keith A; Freishtat, Robert J (2016) Two sampling methods yield distinct microbial signatures in the nasopharynges of asthmatic children. Microbiome 4:25|
|Maltz, Lisa; Matz, Ethan L; Gordish-Dressman, Heather et al. (2016) Sex differences in the association between neck circumference and asthma. Pediatr Pulmonol 51:893-900|
|Castro-Nallar, Eduardo; Shen, Ying; Freishtat, Robert J et al. (2015) Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities. BMC Med Genomics 8:50|
|Jung, Daekyoung; Kim, Bohyoung; Freishtat, Robert J et al. (2015) miRTarVis: an interactive visual analysis tool for microRNA-mRNA expression profile data. BMC Proc 9:S2|
|Pérez-Losada, Marcos; Castro-Nallar, Eduardo; Bendall, Matthew L et al. (2015) Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma. PLoS One 10:e0131819|
|Ferrante, Sarah C; Nadler, Evan P; Pillai, Dinesh K et al. (2015) Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr Res 77:447-54|
|Fu, Liang; Freishtat, Robert J; Gordish-Dressman, Heather et al. (2014) Natural progression of childhood asthma symptoms and strong influence of sex and puberty. Ann Am Thorac Soc 11:939-44|