Association between Early Acute Respiratory Distress Syndrome after Living-Donor Liver Transplantation and Perioperative Serum Biomarkers: The Role of Club Cell Protein 16

Chun-Yu Wu, Ya-Jung Cheng, Ming-Hui Hung, I-Ju Lin, Wei-Zen Sun, Kuang-Cheng Chan, Chun-Yu Wu, Ya-Jung Cheng, Ming-Hui Hung, I-Ju Lin, Wei-Zen Sun, Kuang-Cheng Chan

Abstract

Background: Acute respiratory distress syndrome (ARDS) after living-donor liver transplantation (LDLT) is not uncommon, but it lacks the biomarkers for early detection. Club cell protein 16 (CC16), high-motility group box 1 protein (HMGB1), interleukin-1β (IL-1β), and IL-10 have been reported as relevant to the development of ARDS. However, they have not been investigated during LDLT.

Methods: Seventy-three consecutive recipients undergoing LDLT were enrolled and received the same perioperative care plan. Perioperative serum CC16, HMGB1, IL-1β, and IL-10 levels were measured at the pretransplant state, 30 minutes after reperfusion, postoperative day 1 (POD1), and POD3. ARDS was diagnosed according to the 2012 Berlin definition.

Results: Of the 73 recipients, 13 developed ARDS with significantly longer durations of mechanical ventilation and intensive care unit stay. Serum CC16 levels on POD1 increased significantly from the pretransplant state in the ARDS group but not in the non-ARDS group. Pretransplant serum CC16 levels were also higher in the ARDS group. The area under the receiver operating characteristic curves for POD1 serum CC16 levels used to discriminate ARDS was 0.803 (95% confidence interval: 0.679 to 0.895; p < 0.001). By comparison, HMGB1, IL-1β, and IL-10 were not associated with ARDS after LDLT.

Conclusion: The higher pretransplant serum CC16 level and its increased level on POD1 were associated with the development of early ARDS after LDLT. This trial is registered with NCT01936545, 27 August 2013.

Figures

Figure 1
Figure 1
Changes in perioperative serum anti-inflammatory biomarkers consisting of club cell protein 16 (CC16) (Figure 1(a)) and interleukin-10 (IL-10) (Figure 1(b)) in nonacute respiratory distress syndrome (ARDS) and ARDS groups. indicates a significant difference of p < 0.05 between the groups. # indicates a significant change compared with the pretransplant state of p < 0.05 within the groups.
Figure 2
Figure 2
Changes in perioperative proinflammatory biomarkers consisting of high-motility group box 1 protein (HMGB1) (Figure 2(a)) and interleukin-1β (IL-1β) (Figure 2(b)) in nonacute respiratory distress syndrome (ARDS) and ARDS groups.
Figure 3
Figure 3
Receiver operating characteristic curves describing the ability of serum club cell protein 16 (CC16) levels early in the morning on postoperative day 1 in discriminating early postoperative acute respiratory distress syndrome.

References

    1. Levesque E., Hoti E., Azoulay D., et al. Pulmonary complications after elective liver transplantation-incidence, risk factors, and outcome. Transplantation. 2012;94(5):532–538. doi: 10.1097/TP.0b013e31825c1d41.
    1. Aduen J. F., Stapelfeldt W. H., Johnson M. M., et al. Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation. Liver Transplantation. 2003;9(7):764–771. doi: 10.1053/jlts.2003.50103.
    1. Zhang A., Chi X., Luo G., et al. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation. PLoS ONE. 2013;8(10) doi: 10.1371/journal.pone.0075262.e75262
    1. Fang H., Liu A., Dirsch O., Dahmen U. Liver transplantation and inflammation: Is lipopolysaccharide binding protein the link? Cytokine. 2013;64(1):71–78. doi: 10.1016/j.cyto.2013.07.025.
    1. Brenner T., Fleming T. H., Spranz D., et al. Reactive metabolites and AGE-RAGE-mediated inflammation in patients following liver transplantation. Mediators of Inflammation. 2013;2013:10. doi: 10.1155/2013/501430.501430
    1. Feltracco P., Carollo C., Barbieri S., Pettenuzzo T., Ori C. Early respiratory complications after liver transplantation. World Journal of Gastroenterology. 2013;19(48):9271–9281. doi: 10.3748/wjg.v19.i48.9271.
    1. Pirat A., Özgur S., Torgay A., Candan S., Zeyneloğlu P., Arslan G. Risk factors for postoperative respiratory complications in adult liver transplant recipients. Transplantation Proceedings. 2004;36(1):218–220. doi: 10.1016/j.transproceed.2003.11.026.
    1. Broeckaert F., Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clinical & Experimental Allergy. 2000;30(4):469–475. doi: 10.1046/j.1365-2222.2000.00760.x.
    1. Arsalane K., Broeckaert F., Knoops B., Wiedig M., Toubeau G., Bernard A. Clara cell specific protein (CC16) expression after acute lung inflammation induced by intratracheal lipopolysaccharide administration. American Journal of Respiratory and Critical Care Medicine. 2000;161(5):1624–1630. doi: 10.1164/ajrccm.161.5.9812157.
    1. Determann R. M., Millo J. L., Waddy S., Lutter R., Garrard C. S., Schultz M. J. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study. BMC Pulmonary Medicine. 2009;9, article 49 doi: 10.1186/1471-2466-9-49.
    1. Michel O., Murdoch R., Bernard A. Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings. The Journal of Allergy and Clinical Immunology. 2005;115(6):1143–1147. doi: 10.1016/j.jaci.2005.01.067.
    1. Sarafidis K., Stathopoulou T., Diamanti E., et al. Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates. European Journal of Pediatrics. 2008;167(11):1297–1303. doi: 10.1007/s00431-008-0712-3.
    1. Fernandez-Bustamante A., Klawitter J., Repine J. E., et al. Early effect of tidal volume on lung injury biomarkers in surgical patients with healthy lungs. Anesthesiology. 2014;121(3):469–481. doi: 10.1097/ALN.0000000000000301.
    1. Determann R. M., Wolthuis E. K., Choi G., et al. Lung epithelial injury markers are not influenced by use of lower tidal volumes during elective surgery in patients without preexisting lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2008;294(2):L344–L350. doi: 10.1152/ajplung.00268.2007.
    1. Blondonnet R., Constantin J.-M., Sapin V., Jabaudon M. A pathophysiologic approach to biomarkers in acute respiratory distress syndrome. Disease Markers. 2016;2016:20. doi: 10.1155/2016/3501373.3501373
    1. Lappalainen U., Whitsett J. A., Wert S. E., Tichelaar J. W., Bry K. Interleukin-1β causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. American Journal of Respiratory Cell and Molecular Biology. 2005;32(4):311–318. doi: 10.1165/rcmb.2004-0309oc.
    1. Peñaloza H. F., Nieto P. A., Muñoz-Durango N., et al. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae. The Journal of Immunology. 2015;146(1):100–112. doi: 10.1111/imm.12486.
    1. Shanley T. P., Vasi N., Denenberg A. Regulation of chemokine expression by IL-10 in lung inflammation. Cytokine. 2000;12(7):1054–1064. doi: 10.1006/cyto.1999.0655.
    1. Sziksz E., Pap D., Lippai R., et al. Fibrosis related inflammatory mediators: role of the IL-10 cytokine family. Mediators of Inflammation. 2015;2015:p. 764641.
    1. Chan K.-C., Wu C.-Y., Hung M.-H., Lee P.-H., Cheng Y.-J. Patterns of perioperative thoracic fluid indices changes in liver transplantation with or without postoperative acute lung injury. Journal of the Formosan Medical Association. 2017;116(6):432–440. doi: 10.1016/j.jfma.2016.08.001.
    1. Della Rocca G., Costa M. G., Coccia C., Pompei L., Pietropaoli P. Preload and haemodynamic assessment during liver transplantation: A comparison between the pulmonary artery catheter and transpulmonary indicator dilution techniques. European Journal of Anaesthesiology. 2002;19(12):868–875. doi: 10.1017/S0265021502001394.
    1. Bernard G. R., Artigas A., Brigham K. L., et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. American Journal of Respiratory and Critical Care Medicine. 1994;149(3):818–824. doi: 10.1164/ajrccm.149.3.7509706.
    1. Ranieri V. M., Rubenfeld G. D., Thompson B. T., et al. Acute respiratory distress syndrome: the Berlin definition. The Journal of the American Medical Association. 2012;307(23):2526–2533. doi: 10.1001/jama.2012.5669.
    1. Liu D., Luo G., Luo C., Wang T., Sun G., Hei Z. Changes in the concentrations of mediators of inflammation and oxidative stress in exhaled breath condensate during liver transplantation and their relations with postoperative ARDS. Respiratory Care. 2015;60(5):679–688. doi: 10.4187/respcare.03311.
    1. Pandit J. J. The analysis of variance in anaesthetic research: Statistics, biography and history. Anaesthesia. 2010;65(12):1212–1220. doi: 10.1111/j.1365-2044.2010.06542.x.
    1. DeLong E. R., DeLong D. M., Clarke-Pearson D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–845. doi: 10.2307/2531595.
    1. Benson A. B., Burton J. R., Jr., Austin G. L., et al. Differential effects of plasma and red blood cell transfusions on acute lung injury and infection risk following liver transplantation. Liver Transplantation. 2011;17(2):149–158. doi: 10.1002/lt.22212.
    1. Triulzi D. J. Transfusion-Related Acute Lung Injury: An Update. International Journal of Hematology. 2006;2006(1):497–501. doi: 10.1182/asheducation-2006.1.497.
    1. Goto R., Yamashita K., Aoyagi T., et al. Immunomodulatory effect of nuclear factor-κB inhibition by Dehydroxymethylepoxyquinomicin in combination with donor-specific blood transfusion. Transplantation. 2012;93(8):777–786. doi: 10.1097/TP.0b013e318248ca5f.
    1. Wright J. G., Christman J. W. The role of nuclear factor Kappa B in the pathogenesis of pulmonary diseases: Implications for therapy. American Journal of Respiratory Medicine. 2003;2(3):211–219. doi: 10.1007/BF03256650.
    1. Kropski J. A., Fremont R. D., Calfee C. S., Ware L. B. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. CHEST. 2009;135(6):1440–1447. doi: 10.1378/chest.08-2465.
    1. Lesur O., Langevin S., Berthiaume Y., et al. Outcome value of Clara cell protein in serum of patients with acute respiratory distress syndrome. Intensive Care Medicine. 2006;32(8):1167–1174. doi: 10.1007/s00134-006-0235-1.
    1. Shah R. J., Wickersham N., Lederer D. J., et al. Preoperative plasma club (Clara) cell secretory protein levels are associated with primary graft dysfunction after lung transplantation. American Journal of Transplantation. 2014;14(2):446–452. doi: 10.1111/ajt.12541.
    1. Keswani R. N., Ahmed A., Keeffe E. B. Older age and liver transplantation: A review. Liver Transplantation. 2004;10(8):957–967. doi: 10.1002/lt.20155.
    1. Moine O. L., Marchhant A., Durand F., et al. Systemic release of interleukin-10 during orthotopic liver transplantation. Hepatology. 1994;20(4):889–892. doi: 10.1002/hep.1840200417.
    1. Trifunović J., Miller L., Debeljak Ž., Horvat V. Pathologic patterns of interleukin 10 expression—a review. Biochemia Medica. 2015;25(1):36–48. doi: 10.11613/bm.2015.004.
    1. Jiang X., Tian W., Sung Y. K., Qian J., Nicolls M. R. Macrophages in solid organ transplantation. Vascular Cell. 2014;6(1):p. 5. doi: 10.1186/2045-824X-6-5.
    1. Salehi S., Reed E. F. The divergent roles of macrophages in solid organ transplantation. Current Opinion in Organ Transplantation. 2015;20(4):446–453. doi: 10.1097/MOT.0000000000000209.
    1. Wolfson R. K., Mapes B., Garcia J. G. N. Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3. Microvascular Research. 2014;92:50–55. doi: 10.1016/j.mvr.2013.12.005.
    1. Zhao G., Fu C., Wang L., et al. Down-regulation of nuclear HMGB1 reduces ischemia-induced HMGB1 translocation and release and protects against liver ischemia-reperfusion injury. Scientific Reports. 2017;7(1) doi: 10.1038/srep46272.
    1. Ilmakunnas M., Tukiainen E. M., Rouhiainen A., et al. High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation. Liver Transplantation. 2008;14(10):1517–1525. doi: 10.1002/lt.21573.

Source: PubMed

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