CLINICAL EVALUATION OF POTENTIAL ANTI-INFLAMMATORY EFFECT OF VITAMIN D3 ADJUVANT THERAPY FOR CHRONIC ASTHMA IN IRAQI PATIENTS
Keywords:Asthma, Endogenous vitamin D3, Pulmonary function test, Anti-Inflammatory markers
Objective: This study was designed to evaluate the potential anti-inflammatory effect of vitamin D3 supplementation in Iraqi patients with chronic asthma.
Methods: Forty-four candidate patients were diagnosed with asthma during their visit to hospital allocated as 20 patients assigned to receive conventional therapy for asthma and 24 patients assigned to receive conventional therapy for asthma plus 2000 I. U vitamin D3 tablet for three months period. Also, 30 apparently healthy subjects were included in the study as a control group. Pulmonary function test, serum 25-OH vitamin D levels, serum Interlukin-10 (IL-10) levels, serum tumor necrosis factor alpha (TNF-Î±) levels were measured before and after three months therapy.
Results: After three months treatment, there was a highly significant improvement in both measured and percentage of predicted value of pulmonary function test (PFT) compared to the pre-treatment value for both group 1 and group 2 patients (p<0.01). Also, a highly significant increase in total endogenous vitamin D level in group 2 when compared to group 1 patients after three months period (p<0.01). Group 2 patients presented with a significant increase in mean IL-10 after three months of treatment when compared to pre-treatment level (p<0.05). The mean TNF-Î± level was increased non-significantly in both study groups, but the higher level was found in group 1 patients than in group 2 patients when compared to pre-treatment level (p>0.05).
Conclusion: There was a significant increase in the level of anti-inflammatory biomarker interleukin-10 (IL-10), though no clear effect on tumor necrosis factor-Î± (TNF-Î±) was noticed after three months treatment with vitamin D3 supplementation.
Self TH, Chrisman CR, Finch CK. Asthma. In: Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, et al. Koda-kimble and Young's applied therapeutics: the clinical use of drugs. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2013. p. 565-600.
Barnes PJ. Asthma. In: Loscalzo J, Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, et al. Harrison's pulmonary and critical care medicine. New York: McGraw-Hill; 2010. p. 60-78.
John M, Lim S, Seybold J, Jose P, Robichaud A, O'Connor B, et al. Inhaled corticosteroids increase IL-10 but reduce MIP-1a, GM-CSF and IFN-Î³ release from alveolar macrophages in asthma. Am J Respir Crit Care Med 1998;157:256-62.
Barnes PJ. Pathophysiology of asthma. ERS J 2003;23:84-113.
Lange NE, Litonjua A, Hawrylowicz CM, Weiss S. Vitamin D, the immune system and asthma. Expert Rev Clin Immunol 2009;5:693-702.
Iqbal SF, Freishtat RJ. Mechanism of action of vitamin D in the asthmatic lung. J Investig Med 2011;59:1200-2.
Nagy L, Szanto A, Szatmari I, Szeles L. Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response. Physiol Rev 2012;92:739-89.
Pfeffer PE, Hawrylowicz CM. Vitamin D and lung disease. Thorax 2012;67:1018-20.
Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 2008;181:7090-9.
Brennan A, Katz DR, Nunn JD, Barker S, Hewison M, Fraher LJ, et al. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxy-cholecalciferol. Immunology 1987;61:457-61.
Korf H, Wenes M, Stijlemans B, Takiishi T, Robert S, Miani M, et al. 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism. Immunobiology 2012;217:1292-300.
Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, et al. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signalling via targeting microRNA-155-SOCS1 in macrophages. J Immunol 2013;190:3687-95.
Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012;188:2127-35.
Berraies A, Hamzaoui K, Hamzaoui A. Link between vitamin D and airway remodeling. J Asthma Allergy 2014;7:23-30.
Xystrakis E, Kusumakar S, Boswell S, Peek E, Urry Z, Richards DF, et al. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006;116:146-55.
Clifford RL, Knox AJ. Vitamin D-A new treatment for airway remodelling in asthma? Br J Pharmacol 2009;158:1426-8.
Zhang Y, Leung DY, Goleva E. Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma. J Allergy Clin Immunol 2014;133:1744-52.
Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DY. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol 2010;125:995-1000.
Sandhu MS, Casale TB. The role of vitamin D in asthma. Ann Allergy Asthma Immunol 2010;105:191-9.
Riccioni G, D'Orazio N. The role of selenium, zinc and antioxidant vitamin supplementation in the treatment of bronchial asthma: adjuvant therapy or not? Expert Opin Investig Drugs 2005;14:1145-55.
Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child 1996;75:494-7.
Hussain MS, Abdulridha MK, Khudhair MS. Anti-inflammatory, antioxidant, and vasodilating effect of evening primrose oil in type 2 diabetic patients. Int J Pharm Sci Rev Res 2016;39:173-8.
Skobeloff EM, Spivey WH, St Clair SS, Schoffstall JM. The influence of age and sex on asthma admissions. JAMA 1992;268:3437-40.
Al-Kubaisy W, Ali SH, Al-Thamiri D. Risk factors for asthma among primary school children in Baghdad, Iraq. Saudi Med J 2005;26:460-6.
Paaso EM, Jaakkola MS, Lajunen TK, Hugg TT, Jaakkola JJ. The importance of family history in asthma during the first 27 y of life. Am J Respir Crit Care Med 2013;188:624-6.
Von ME. The environmental predictors of allergic disease. J Allergy Clin Immunol 2000;105:9-19.
Jie Y, Isa ZM, Jie X, Ju ZL, Ismail NH. Urban vs. rural factors that affect adult asthma. Rev Environ Contam Toxicol 2013;226:33-63.
Musafiri S, van Meerbeeck J, Musango L, Brusselle G, Joos G, Seminega B, et al. Prevalence of atopy, asthma and COPD in an urban and a rural area of an African country. Respir Med 2011;105:1596-605.
Ellison-Loschmann L, King R, Pearce N. Regional variations in asthma hospitalisations among Maori and non-Maori. N Z Med J 2004;117:U745.
Columbo M, Panettieri RA Jr, Rohr AS. Asthma in the elderly: a study of the role of vitamin D. Allergy Asthma Clin Immunol 2014;10:48.
Nageswari AD, Rajanandh MG, Priyanka RK, Rajasekhar P. Effect of vitamin D3 on mild to moderate persistent asthmatic patients: a randomised controlled pilot study. Perspect Clin Res 2014;5:167-71.
Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of viÂ¬tamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005;135:317-22.
Menon B, Nima G, Dogra V, Mittal A, Kaur C, Mittal U. Evaluation of vitamin D in bronchial asthma and the effect of vitamin D supplementation on asthma severity and control: a randomised control trial. Eur Respir J 2014;44:4049.
Miyake Y, Sasaki S, Tanaka K, Hirota Y. Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Respir J 2010;35:1228-34.
Aldubi HM, Alissa EM, Kamfar HZ, Gaber O, Marzouki ZM. Bronchial asthma and hypovitaminosis D in Saudi children. Asian Pac Allergy 2015;5:103-13.
Gupta A, Bush A, Richards D, Hawrylowicz C, Saglani S. Serum vitamin D levels and severe therapy-resistant asthma in children. Arch Dis Child 2011;96:A13.
Korn S, HÃ¼bner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res 2013;14:25.
Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol 2008;121:5-10.
Peterson CA, Heffernan ME. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (Lond) 2008;5:10.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol 2011;7:337-45.
Lan N, Luo G, Yang X, Cheng Y, Zhang Y, Wang X, et al. 25-Hydroxy vitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation. PLoS One 2014;9:e111599.
Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DY. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med 2010;181:699-704.