Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: a case-control study

Nicolas Barnett, Zhiguo Zhao, Tatsuki Koyama, David R Janz, Chen-Yu Wang, Addison K May, Gordon R Bernard, Lorraine B Ware, Nicolas Barnett, Zhiguo Zhao, Tatsuki Koyama, David R Janz, Chen-Yu Wang, Addison K May, Gordon R Bernard, Lorraine B Ware

Abstract

Background: The aim of this study was to determine the association between 25-hydroxyvitamin D (25-OHD) levels at the onset of critical illness and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with sepsis or trauma.

Methods: We performed two nested case-control studies of 478 patients with sepsis and trauma with or without ALI/ARDS admitted to the medical, surgical and trauma ICUs of a tertiary-care center. Cases consisted of patients with either sepsis or trauma and ALI/ARDS; controls consisted of equivalent numbers of matched patients with either sepsis or trauma alone. We measured serum 25-OHD levels the morning after ICU admission and used multivariable regression to assess the relationship between 25-OHD and diagnosis of ALI/ARDS during the first four ICU days, controlling for age, gender, diabetes, smoking status and season.

Results: 25-OHD levels did not differ between cases with ALI/ARDS and controls in either the sepsis or trauma cohorts. Using a conditional logistic regression model, sepsis patients during the winter season with higher 25-OHD levels were more likely to develop acute lung injury (odds ratio 1.68, 95% confidence interval of 1.05 to 2.69, P = 0.03). This association did not hold for the trauma cohort in either season. Sepsis and trauma patients had a lower risk of hospital mortality at higher 25-OHD levels but neither relationship reached significance. Higher one-year mortality after trauma was associated with lower 25-OHD levels (HR 0.50, CI 0.35,0.72 P = 0.001).

Conclusions: Serum 25-OHD measured early after admission to intensive care is not associated with the development of acute lung injury, hospital or one-year mortality in critically ill patients with sepsis although lower 25-OHD levels were associated with higher one-year mortality in patients with severe trauma.

Figures

Figure 1
Figure 1
Box plot summary of 25-hydroxyvitamin D (25-OHD) levels by cohort and case-control status. Twenty-five-OHD levels were not significantly different between patients with or without acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Horizontal bars represent medians, boxes encompass the 25th to 75th percentile and error bars encompass the 10th to 90th percentile.
Figure 2
Figure 2
Forest plot summary of logistic regression analysis for risk of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in the sepsis cohort. Higher vitamin D levels in winter were associated with a higher odds ratio (OR) for developing ALI/ARDS: OR 1.68 (95% CI 1.054 to 2.69), (P = 0.03). OR (black dots) and the corresponding CIs (black lines) for the risk of ALI/ARDS for each covariate are shown.
Figure 3
Figure 3
Forest plot of logistic regression analysis for risk of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in the trauma cohort. Vitamin D levels were not associated with risk of ALI/ARDS in severe trauma. Odds ratio (black dots) and the corresponding confidence intervals (black lines) for the risk of ALI/ARDS for each covariate are shown.

References

    1. Peterlik M, Grant WB, Cross HS. Calcium, vitamin D and cancer. Anticancer Res. 2009;4(9):3687–3698.
    1. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;4(11):1174–1180. doi: 10.1001/archinte.168.11.1174.
    1. Takiishi T, Gysemans C, Bouillon R, Mathieu C. Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2010;4(2):419–446. doi: 10.1016/j.ecl.2010.02.013.
    1. Searing DA, Leung DY. Vitamin D in atopic dermatitis, asthma and allergic diseases. Immunol Allergy Clin North Am. 2010;4(3):397–409. doi: 10.1016/j.iac.2010.05.005.
    1. Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev. 2010;4(7):507–510. doi: 10.1016/j.autrev.2010.02.011.
    1. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;4(1):113–119. doi: 10.1093/ije/dym247.
    1. Mirkovic K, van den Born J, Navis G, de Borst MH. Vitamin D in chronic kidney disease: new potential for intervention. Curr Drug Targets. 2011;4(1):42–53. doi: 10.2174/138945011793591572.
    1. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the third national health and nutrition examination survey. Arch Intern Med. 2009;4(4):384–390. doi: 10.1001/archinternmed.2008.560.
    1. Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J. 2001;4(14):2579–2585. doi: 10.1096/fj.01-0433rev.
    1. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;4(16):1730–1737. doi: 10.1001/archinte.167.16.1730.
    1. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011;4 CD007470.
    1. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zugel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A. et al.Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;4(2):361–370. doi: 10.1002/eji.200425995.
    1. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008;4(1):G208–G216.
    1. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;4(5768):1770–1773. doi: 10.1126/science.1123933.
    1. Lagishetty V, Misharin AV, Liu NQ, Lisse TS, Chun RF, Ouyang Y, McLachlan SM, Adams JS, Hewison M. Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinol. 2010;4(6):2423–2432. doi: 10.1210/en.2010-0089.
    1. Pistolic J, Cosseau C, Li Y, Yu JJ, Filewod NC, Gellatly S, Rehaume LM, Bowdish DM, Hancock RE. Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway. J Innate Immun. 2009;4(3):254–267. doi: 10.1159/000171533.
    1. Schauber J, Oda Y, Buchau AS, Yun QC, Steinmeyer A, Zugel U, Bikle DD, Gallo RL. Histone acetylation in keratinocytes enables control of the expression of cathelicidin and CD14 by 1,25-dihydroxyvitamin D3. J Invest Dermatol. 2008;4(4):816–824. doi: 10.1038/sj.jid.5701102.
    1. Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically ill patients. N Engl J Med. 2009;4(18):1912–1914. doi: 10.1056/NEJMc0809996.
    1. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, Tangpricha V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;4:28. doi: 10.1186/1479-5876-7-28.
    1. McKinney JD, Bailey BA, Garrett LH, Peiris P, Manning T, Peiris AN. Relationship between vitamin D status and ICU outcomes in veterans. J Am Med Dir Assoc. 2011;4(3):208–211. doi: 10.1016/j.jamda.2010.04.004.
    1. Venkatram S, Chilimuri S, Adrish M, Salako A, Patel M, Diaz-Fuentes G. Vitamin D deficiency as associated with mortality in the medical intensive care unit. Crit Care. 2011;4(6):R292. doi: 10.1186/cc10585.
    1. Braun A, Chang D, Mahadevappa K, Gibbons FK, Liu Y, Giovannucci E, Christopher KB. Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill*. Crit Care Med. 2011;4(4):671–677. doi: 10.1097/CCM.0b013e318206ccdf.
    1. Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality*. Crit Care Med. 2012;4(1):63–72. doi: 10.1097/CCM.0b013e31822d74f3.
    1. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;4(18):1334–1349. doi: 10.1056/NEJM200005043421806.
    1. Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest. 2012;4(8):2731–2740. doi: 10.1172/JCI60331.
    1. van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;4(1–2):93–101.
    1. Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L, Kavtaradze N, Uphoff I, Hooper C, Tangpricha V, Alexander RW, Brigham K, Quyyumi AA. et al.Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011;4(2):186–192. doi: 10.1016/j.jacc.2011.02.051.
    1. O’Neal HR Jr, Koyama T, Koehler EA, Siew E, Curtis BR, Fremont RD, May AK, Bernard GR, Ware LB. Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med. 2011;4(6):1343–1350. doi: 10.1097/CCM.0b013e3182120992.
    1. Siew ED, Ware LB, Gebretsadik T, Shintani A, Moons KG, Wickersham N, Bossert F, Ikizler TA. Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. J Am Soc Nephrol. 2009;4(8):1823–1832. doi: 10.1681/ASN.2008070673.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;4(10):818–829. doi: 10.1097/00003246-198510000-00009.
    1. Baker SP, O’Neill B, Haddon W Jr, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;4(3):187–196. doi: 10.1097/00005373-197403000-00001.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;4(4):1250–1256. doi: 10.1097/01.CCM.0000050454.01978.3B.
    1. Bernard G. The Brussels score. Sepsis. 1997;4(1):43–44. doi: 10.1023/A:1009711301483.
    1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;4(3 Pt 1):818–824.
    1. Gallicchio L, Helzlsouer KJ, Chow WH, Freedman DM, Hankinson SE, Hartge P, Hartmuller V, Harvey C, Hayes RB, Horst RL, Koenig KL, Kolonel LN, Laden F, McCullough ML, Parisi D, Purdue MP, Shu X-O, Snyder K, Stolzenberg-Solomon RZ, Tworoger SS, Varanasi A, Virtamo J, Wilkens LR, Xiang Y-B, Yu K, Zeleniuch-Jacquotte A, Zheng W, Abnet CC, Albanes D, Bertrand K. et al.Circulating 25-hydroxyvitamin D and the risk of rarer cancers: design and methods of the cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol. 2010;4(1):10–20. doi: 10.1093/aje/kwq116.
    1. Horst RL. Exogenous versus endogenous recovery of 25-hydroxyvitamins D2 and D3 in human samples using high-performance liquid chromatography and the DiaSorin LIAISON Total-D Assay. J Steroid Biochem Mol Biol. 2010;4(1–2):180–182.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;4(3):266–281. doi: 10.1056/NEJMra070553.
    1. Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D. Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Med. 2010;4(6):1609–1611.
    1. Ryz NR, Patterson SJ, Zhang Y, Ma C, Huang T, Bhinder G, Wu X, Chan J, Glesby A, Sham HP, Dutz JP, Leving MK, Jacobson K, Vallance BA. et al.Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses. Am J Physiol Gastrointest Liver Physiol. 2012;4(12):G1299–G1311. doi: 10.1152/ajpgi.00320.2012.
    1. Gama R, Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, Chugh S, Deshpande S, Ford C. Hypovitaminosis D and disease: consequence rather than cause? BMJ. 2012;4:e5706. doi: 10.1136/bmj.e5706.
    1. Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. J Am Soc Nephrol. 2008;4(9):1741–1752. doi: 10.1681/ASN.2007060666.
    1. Krishnan A, Ochola J, Mundy J, Jones M, Kruger P, Duncan E, Venkatesh B. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care. 2010;4(6):R216. doi: 10.1186/cc9341.
    1. Laupland KB, Svenson LW, Grant V, Ball CG, Mercado M, Kirkpatrick AW. Long-term mortality outcome of victims of major trauma. Injury. 2010;4(1):69–72. doi: 10.1016/j.injury.2009.06.006.
    1. Hoffmann M, Lefering R, Gruber-Rathmann M, Rueger JM, Lehmann W. The impact of BMI on polytrauma outcome. Injury. 2012;4(2):184–188. doi: 10.1016/j.injury.2011.05.029.
    1. McCullough ML, Weinstein SJ, Freedman DM, Helzlsouer K, Flanders WD, Koenig K, Kolonel L, Laden F, Le Marchand L, Purdue M, Snyder K, Stevens VL, Stolzenberg-Solomon R, Virtamo J, Yang G, Yu K, Zheng W, Albanes D, Ashby J, Bertrand K, Cai H, Chen Y, Gallicchio L, Giovannucci E, Jacobs EJ, Hankinson SE, Hartge P, Hartmuller V, Harvey C, Hayes RB. et al.Correlates of circulating 25-hydroxyvitamin D: cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol. 2010;4(1):21–35. doi: 10.1093/aje/kwq113.
    1. Higgins DM, Wischmeyer PE, Queensland KM, Sillau SH, Sufit AJ, Heyland DK. Relationship of vitamin D deficiency to clinical outcomes in critically Ill patients. JPEN J Parenter Enteral Nutr. 2012;4(6):713–720. doi: 10.1177/0148607112444449.
    1. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS, Blackwell S, Kinsella J, McMillan DC, Wallace AM. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr. 2011;4(5):1006–1011. doi: 10.3945/ajcn.110.008490.
    1. Louw JA, Werbeck A, Louw ME, Kotze TJ, Cooper R, Labadarios D. Blood vitamin concentrations during the acute-phase response. Crit Care Med. 1992;4(7):934–941. doi: 10.1097/00003246-199207000-00007.
    1. Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R. Bone turnover in prolonged critical illness: effect of vitamin D. J Clin Endocrinol Metab. 2003;4(10):4623–4632. doi: 10.1210/jc.2003-030358.
    1. Chun RF, Lauridsen AL, Suon L, Zella LA, Pike JW, Modlin RL, Martineau AR, Wilkinson RJ, Adams J, Hewison M. Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 2010;4(7):3368–3376. doi: 10.1210/jc.2010-0195.
    1. Miller PR, Croce MA, Kilgo PD, Scott J, Fabian TC. Acute respiratory distress syndrome in blunt trauma: identification of independent risk factors. Am Surg. 2002;4(10):845–850. Discussion 850-841.
    1. Lee P, Nair P, Eisman JA, Center JR. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality? Intensive Care Med. 2009;4(12):2028–2032. doi: 10.1007/s00134-009-1642-x.
    1. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.
    1. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, Andersen PL, Glerup H, Sodemann M. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;4(9):843–850. doi: 10.1164/rccm.200804-567OC.
    1. Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, Walraven G, Chandramohan D. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet. 2012;4(9824):1419–1427. doi: 10.1016/S0140-6736(11)61650-4.
    1. Sokol SI, Srinivas V, Crandall JP, Kim M, Tellides G, Lebastchi A, Yu Y, Gupta AK, Alderman MH. The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vasc Med. 2012;4(6):394–404. doi: 10.1177/1358863X12466709.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner