The Role of Vitamin D Deficiency as a Risk Factor for Acute Lung Injury in Severe Sepsis

Transcription

1 The Role of Vitamin D Deficiency as a Risk Factor for Acute Lung Injury in Severe Sepsis Nurnaningsih Pediatric Emergency & Intensive Care Working Group 7 th Indonesian Picu-Nicu Update, Yogyakarta, April 2015

2 Outline To understand the metabolism of vitamin D To understand mechanisme of vitamin D as an innate immunity and adaptive immunity To understand the affect of vitamin D deficiency as a risk factor for acute lung injury in severe sepsis

3 Introduction Function of vitamin D: Classical action Regulating level of calcium and phosphorus. enhances intestinal calcium and phosphate absorption, Mineralization of bone. stimulates osteoclast differentiation and calcium reabsorption Non classical actions anticancer effects Immunomodulator Prietl B et al. Vitamin D and immune function. Nutrients,2013,5, Roy S et al. Vitamin D sensitivity to the immune responses and autoimmunity: Achemical network model study

4 Definition of Vitamin D Status (Endocrine Society) : Deficiency <20 ng/ml (50 nmol/l) Insufficiency ng/ml (52 72 nmol/l) Sufficiency >30 ng/ml (75 nmol/l) Prietl, 2013

5 Function of vitamin D as an immunomodulator: > 2000s 1900s 1849s William : First therapeutic in curing over 400 tuberculosis patients with cord-liver oil Niels Finsen (Nobel prize) : Usage of UV exposure to treat over 800 pts affected by lupus vulgaris Rey, 2013: 1 st prospective study. Hypovitaminosis D was high at PICU admission. Prietl, 2013: Vit D as a promising and relatively safe for new strategies in the prevention and adjunctive treatment of disease caused by impaired immune homeostasis Pletz, 2014: Supplementation of non activated vit D to protect from pneumonia may be non sufficient in patients that have a decreased capacity to hydroxylate 25-OH to 1,25-OH2

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7 VITAMIN D AS AN INNATE IMMUNITY AND ADAPTIVE IMMUNITY

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10 The role of vitamin D in sepsis Patients with severe infections as in sepsis have a high prevalence of vitamin D deficiency and high mortality rates The role of vitamin D in sepsis syndrome has not been fully evaluated in humans animal models of ALI demonstrate that intratracheal administration of vitamin D can reduce neutrophil recruitment to the lung Jeng L et al, Journal of Translational Medicine :28 Boyle et al, BMC Medicine 2013, 11:166

11 Journal of Translational Medicine 2009, 7:28 Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. Leo Jeng1, Alexandra V Yamshchikov2, Suzanne E Judd3, Henry M Blumberg2,Gregory S Martin4, Thomas R Ziegler1,3,5 and Vin Tangpricha*1,3,5,6 Conclusion: an association between critical illness and lower 25(OH)D and DBP levels in critically ill patients as compared to healthy controls

12 Vitamin D status in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects. p <

13 Anti-microbial peptide cathelicidin (LL-37) in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects p < 0.001

14 Pediatrics 2012;130:1 8 Conclusion : a high prevalence of vitamin D deficiency in critically ill children and an inverse association between 25(OH)D levels and illness severity

15 J Pediatr (Rio J). 2014;90: Vitamin D deficiency at pediatric intensive care admission. Rey C,, Sánchez-Arangob D, López-Hercec J, Martínez- Camblord P, García-Hernándeze I, Prietof B, Pallavicinig Z

16 Hari Ini pada 5:45 AM Conclusion: This study demonstrates an association between critical illness(sepsis) and lower 25(OH)D,and plasma LL-37 in critically ill patients as compared to healthy controls. It also establishes a positive association between vitamin D status and plasma LL-37, which suggests that systemic LL-37 levels may be regulated by vitamin D status.

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18 Thorax 2013;68(Suppl 3):A1 A220 VITAMIN D DEFICIENCY INCREASES BACTERIAL LOAD IN A MURINE MODEL OF SEPSIS-INDUCED LUNG INJURY 1D Parekh, 2RCA Dancer, 2S Lax, 1GD Perkins, 2DR Thickett; 1University of Warwick,Warwick, UK; 2University of Birmingham, Birmingham, UK ConclusionVitamin D deficiency significantly increases the bacterial load both systemically, locally and within the lung in a murine model of peritonitis. This is associated with an increase in tissue permeability locally and within the lung.

19 It is the first study to investigate the association of ALI/ARDS in critical illness with 25-OHD levels.

20 39.0 nmol/l, 45.8 nmol/l 50.8 nmol/l 54.9nmol/L P = 0.12 P = 0.30

21 On going study : Patient recruitment commenced in September 2012 and is expected to run for two years (last patient recruited in August 2014).

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23 Summary Vitamin D has profound effects on human immunity acting as an immune system modulator Deficiency of vitamin D is common in pediatric critically ill as a severe sepsis vitamin D deficiency associated with higher mortality rates Vitamin D defisiency was not an independent risk factor for developing ALI

24 THANK YOU