Vitamin D and Airway inflammation in Adolescent Asthmatics
Douglas M. Mansell1, 2, 3. 1Pulmonary Critical care, SUNY Downstate, Brooklyn, New York, United States, 2Clinical Epidemiology, Weill Cornell Medicine, New York, New York, United States, 3GenMed, Childrens National Health System, Washington, District of Columbia, United States
Purpose of Study The high prevalence of vitamin D insufficiency has been shown to correlate with the high prevalence of asthma in urban youth. Although underlying mechanisms are not clear, vitamin D may regulate inflammation by increased production of anti-inflammatory compounds (Il-10, cAMP, MKP1). Therefore, the objective of this study is to determine which anti-inflammatory mediators are differentially expressed in asthmatic epithelium when exposed to 25(OH)D in conjunction with dexamethasone. The hypothesis is that low levels of vitamin D will be associated with a more pronounced inflammatory milieu and reduced anti-inflammatory response.
Methods Used Nasal Epithelial cells were cultured for 90 minutes ex vivo with varying levels of Dexamethasone with or without 25(OH)D (6 conditions). mRNA was profiled using Illumina and validated using NanoString. Network and functional analyses were performed using Ingenuity Pathway Analysis. Confirmatory experiments were performed on human asthmatic and non-asthmatic bronchial epithelial cells exposed to 25(OH)D with or without Dex. Intracellular cAMP was measured with ELISA.
Summary of Results Of 214 AsthMaP2 participants, 53% were male and (97%) had persistent asthma.
The mean (SE) age=10.9(0.4) years, BMI percentile for age=72.1(3)%, and serum
25(OH)D=19.5(0.9) ng/mL. Whole transcriptome analyses of nasal epithelial cells (n=7) showed
34 transcripts differentially expressed in all exposure conditions (p≤0.01). Pathways analysis identified cAMP signaling as a top activated pathway impacted by 25(OH)D. Intracellular cAMP levels were 10-fold higher in asthmatic (n=3) vs. non-asthmatic (n=3) tracheal bronchial epithelial cells at baseline (p=0.009). While this difference persisted through 15 minutes of exposure to 25(OH)D with or without DEX, there were no significant changes in intracellular cAMP from baseline in response to exposure conditions.
Conclusions Data show that cAMP is constitutively expressed higher in asthmatics in comparison to non-asthmatics, manipulations of vitamin D level did not alter cAMP levels. Additional experiments using a larger sample size are required to further test the proposed effects of vitamin D, with a special focus on cAMP as a transient mediator of inflammation regulation in asthmatic airways.
Back to 2019 Abstracts