25-Hydroxyvitamin D, biomarkers of eosinophilic inflammation, and airway remodeling in children with newly diagnosed untreated asthma.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE: We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS: The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS: Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION: In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.

Potential Markers in Cardiac Hypertrophy?

Cardiomyopathies are diagnosed based on medical history of patient (symptoms and family history), physical examination, results of echocardiogram and in some situations additionally ECG or chest-X-ray results. Currently used non-invasive diagnostic methods, could be complemented by biochemical tests. In this review some emerging potential biomarkers such as: osteopontin, ST-2 receptor, osteoprotegerin, neopterin, urocortins, growth differentiation factor 15 and urotensin II are described. In current article human and non human investigations have been reviewed, since rat is most commonly used model in experimental cardiology and gives important foundations to clinical knowledge.

Association Between Vitamin D Deficiency and Allergic Diseases.

Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor.

The Role of IL-33 in the Inflammation Process of Asthma and Atherosclerosis.

Interleukin-33 (IL-33) is a newly found cytokine of the interleukin-1 (IL-1) family. It's mainly expressed by epithelial and endothelial cells. This expression is upregulated by pro-inflammatory stimulation, thus has an important role in inflammatory responses, such as hypersensitive diseases (asthma), autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (heart failure) and neurodegenerative diseases (Alzheimer). Several studies explored the complicated mechanism of IL-33 action in asthma and atherosclerosis, as this IL is significantly increased in these pathologies, and suggested its potential use in the therapeutic procedures.