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Published in: BMC Pulmonary Medicine 1/2017

Open Access 01-12-2017 | Research article

Plasma levels of alarmin HNPs 1–3 associate with lung dysfunction after cardiac surgery in children

Authors: XiWang Liu, QiXing Chen, YuJia Luo, YaoQin Hu, DengMing Lai, XiaoLe Zhang, XiangHong Zhang, JianGen Yu, XiangMing Fang, Qiang Shu

Published in: BMC Pulmonary Medicine | Issue 1/2017

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Abstract

Background

Early onset of lung injury is considerable common after cardiac surgery and is associated with increasing in morbidity and mortality, but current clinical predictors for the occurrence of this complication always have limited positive warning value. This study aimed to evaluate whether elevated plasma levels of human neutrophil peptides (HNPs) 1–3 herald impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).

Methods

Consecutive children younger than 3 years old who underwent cardiac surgery were prospectively enrolled. Plasma concentrations of HNPs 1–3 and inflammatory cytokines were measured before, and immediately after CPB, as well as at 1 h, 12 h, and 24 h after CPB.

Results

Thirty patients were enrolled, 18 (60%) of whom were infants. Plasma levels of HNPs 1–3 and the pro-inflammatory cytokine interleukin-6 (IL-6) significantly increased immediately after CPB (P < 0.001), while IL-8 increased 1 h after the CPB operation (P = 0.002). The anti-inflammatory cytokine IL-10 levels were also significantly elevated immediately after CPB compared with the baseline (P < 0.001). The stepwise multiple linear regression analysis showed that the plasma HNPs 1–3 levels immediately after CPB was independent correlated with the declined lung function, as reflected by the PaO2/FiO2 ratio on the first 2 days after operation (for the first day: OR, −1.067, 95% CI, −0.548 to −1.574; P < 0.001; for the second day: OR, −0.667, 95% CI, −0.183 to −1.148; P = 0.009) and prolonged mechanical ventilation time (OR, 0.039, 95% CI, 0.005 to 0.056; P = 0.011). Plasma levels of HNPs 1–3 and IL-10 returned to the baseline values, while IL-6 and IL-8 levels remained significantly higher than baseline 24 h after CPB (P ≤ 0.01).

Conclusions

Elevated HNPs 1–3 levels immediately after CPB correlate with impaired lung function, and HNPs 1–3 could serve as a quantifiable early alarmin biomarker for onset of lung injury in infants and young children undergoing cardiac surgery with CPB.
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Literature
1.
go back to reference Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg. 2013;95(3):1122–9.CrossRefPubMed Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg. 2013;95(3):1122–9.CrossRefPubMed
2.
go back to reference Tuinman PR, Cornet AD, Kuipers MT, Vlaar AP, Schultz MJ, Beishuizen A, et al. Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery. BMC Pulm Med. 2013;13:76.CrossRefPubMedPubMedCentral Tuinman PR, Cornet AD, Kuipers MT, Vlaar AP, Schultz MJ, Beishuizen A, et al. Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery. BMC Pulm Med. 2013;13:76.CrossRefPubMedPubMedCentral
3.
go back to reference Ohata K, Chen-Yoshikawa TF, Menju T, Miyamoto E, Tanaka S, Takahashi M, et al. Protective effect of inhaled rho-kinase inhibitor on lung ischemia-reperfusion injury. Ann Thorac Surg. 2017;103(2):476–83.CrossRefPubMed Ohata K, Chen-Yoshikawa TF, Menju T, Miyamoto E, Tanaka S, Takahashi M, et al. Protective effect of inhaled rho-kinase inhibitor on lung ischemia-reperfusion injury. Ann Thorac Surg. 2017;103(2):476–83.CrossRefPubMed
6.
go back to reference Yang ZH, Ning BT, Zhang CM, Lin R, Ye S, Liu T. Clinical application of extracorporeal membrane oxygenation in children with refractory cardiopulmonary failure. World J Pediatr. 2016;12(3):364–7.CrossRefPubMed Yang ZH, Ning BT, Zhang CM, Lin R, Ye S, Liu T. Clinical application of extracorporeal membrane oxygenation in children with refractory cardiopulmonary failure. World J Pediatr. 2016;12(3):364–7.CrossRefPubMed
7.
go back to reference López-Fernández Y, Azagra AM, de la Oliva P, Modesto V, Sánchez JI, Parrilla J, et al. Pediatric acute lung injury epidemiology and natural history study: incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med. 2012;40(12):3238–45.CrossRefPubMed López-Fernández Y, Azagra AM, de la Oliva P, Modesto V, Sánchez JI, Parrilla J, et al. Pediatric acute lung injury epidemiology and natural history study: incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med. 2012;40(12):3238–45.CrossRefPubMed
8.
go back to reference Mazine A, Rached-D'Astous S, Ducruet T, Lacroix J, Poirier N. Pediatric Acute Lung Injury and Sepsis Investigators Network. Blood transfusions after pediatric cardiac operations: a north American multicenter prospective study. Ann Thorac Surg. 2015;100(2):671–7.CrossRefPubMed Mazine A, Rached-D'Astous S, Ducruet T, Lacroix J, Poirier N. Pediatric Acute Lung Injury and Sepsis Investigators Network. Blood transfusions after pediatric cardiac operations: a north American multicenter prospective study. Ann Thorac Surg. 2015;100(2):671–7.CrossRefPubMed
9.
go back to reference Shi S, Zhao Z, Liu X, Shu Q, Tan L, Lin R, et al. Perioperative risk factors for prolonged mechanical ventilation following cardiac surgery in neonates and young infants. Chest. 2008;134(4):768–74.CrossRefPubMed Shi S, Zhao Z, Liu X, Shu Q, Tan L, Lin R, et al. Perioperative risk factors for prolonged mechanical ventilation following cardiac surgery in neonates and young infants. Chest. 2008;134(4):768–74.CrossRefPubMed
10.
go back to reference Markou T, Chambers DJ. Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: role of mitogen-activated protein kinase/Akt signaling and the effects of theophylline. J Thorac Cardiovasc Surg. 2014;148(5):2335–44.CrossRefPubMedPubMedCentral Markou T, Chambers DJ. Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: role of mitogen-activated protein kinase/Akt signaling and the effects of theophylline. J Thorac Cardiovasc Surg. 2014;148(5):2335–44.CrossRefPubMedPubMedCentral
11.
go back to reference Mazzeffi M, Rock P. Should we prone cardiac surgery patients with acute respiratory distress syndrome? Ann Thorac Surg. 2014;97(3):1122.CrossRefPubMed Mazzeffi M, Rock P. Should we prone cardiac surgery patients with acute respiratory distress syndrome? Ann Thorac Surg. 2014;97(3):1122.CrossRefPubMed
12.
go back to reference Turnbull AE, Ruhl AP, Lau BM, Mendez-Tellez PA, Shanholtz CB, Needham DM. Timing of limitations in life support in acute lung injury patients: a multisite study. Crit Care Med. 2014;42(2):296–302.CrossRefPubMedPubMedCentral Turnbull AE, Ruhl AP, Lau BM, Mendez-Tellez PA, Shanholtz CB, Needham DM. Timing of limitations in life support in acute lung injury patients: a multisite study. Crit Care Med. 2014;42(2):296–302.CrossRefPubMedPubMedCentral
13.
go back to reference Qi YY, Zhou XJ, Cheng FJ, Zhang H. Elevated plasma α-Defensins (HNP1-3) levels correlated with IgA1 glycosylation and susceptibility to IgA nephropathy. Dis Markers. 2016;2016:8123138.CrossRefPubMedPubMedCentral Qi YY, Zhou XJ, Cheng FJ, Zhang H. Elevated plasma α-Defensins (HNP1-3) levels correlated with IgA1 glycosylation and susceptibility to IgA nephropathy. Dis Markers. 2016;2016:8123138.CrossRefPubMedPubMedCentral
14.
15.
go back to reference Chen Q, Jin Y, Zhang K, Li H, Chen W, Meng G, et al. Alarmin HNP-1 promotes pyroptosis and IL-1β release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages. Innate Immun. 2014;20(3):290–300.CrossRefPubMed Chen Q, Jin Y, Zhang K, Li H, Chen W, Meng G, et al. Alarmin HNP-1 promotes pyroptosis and IL-1β release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages. Innate Immun. 2014;20(3):290–300.CrossRefPubMed
16.
go back to reference Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005;6(6):551–7.CrossRefPubMed Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005;6(6):551–7.CrossRefPubMed
17.
go back to reference Baines KJ, Upham JW, Yerkovich ST, Chang AB, Marchant JM, Carroll M, et al. Mediators of neutrophil function in children with protracted bacterial bronchitis. Chest. 2014;146(4):1013–20.CrossRefPubMed Baines KJ, Upham JW, Yerkovich ST, Chang AB, Marchant JM, Carroll M, et al. Mediators of neutrophil function in children with protracted bacterial bronchitis. Chest. 2014;146(4):1013–20.CrossRefPubMed
18.
go back to reference Paone G, Conti V, Vestri A, Leone A, Puglisi G, Benassi F, et al. Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients. Dis Markers. 2011;31(2):91–100.CrossRefPubMedPubMedCentral Paone G, Conti V, Vestri A, Leone A, Puglisi G, Benassi F, et al. Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients. Dis Markers. 2011;31(2):91–100.CrossRefPubMedPubMedCentral
19.
go back to reference Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG. Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma. Thorax. 2011;66(11):942–7.CrossRefPubMed Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG. Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma. Thorax. 2011;66(11):942–7.CrossRefPubMed
20.
go back to reference Ashitani J, Mukae H, Arimura Y, Sano A, Tokojima M, Nakazato M. High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Life Sci. 2004;75(9):1123–34.CrossRefPubMed Ashitani J, Mukae H, Arimura Y, Sano A, Tokojima M, Nakazato M. High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Life Sci. 2004;75(9):1123–34.CrossRefPubMed
21.
go back to reference Wallace AM, He JQ, Burkett KM, Ruan J, Connett JE, Anthonisen NR, et al. Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study. Respir Res. 2006;7:76.CrossRefPubMedPubMedCentral Wallace AM, He JQ, Burkett KM, Ruan J, Connett JE, Anthonisen NR, et al. Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study. Respir Res. 2006;7:76.CrossRefPubMedPubMedCentral
22.
go back to reference Tiriveedhi V, Banan B, Deepti S, Nataraju A, Hachem R, Trulock E, et al. Role of defensins in the pathogenesis of chronic lung allograft rejection. Hum Immunol. 2014;75(4):370–7.CrossRefPubMed Tiriveedhi V, Banan B, Deepti S, Nataraju A, Hachem R, Trulock E, et al. Role of defensins in the pathogenesis of chronic lung allograft rejection. Hum Immunol. 2014;75(4):370–7.CrossRefPubMed
23.
go back to reference Han W, Wang W, Mohammed KA, Alpha-defensins SY. Increase lung fibroblast proliferation and collagen synthesis via the beta-catenin signaling pathway. FEBS J. 2009;276(22):6603–14.CrossRefPubMedPubMedCentral Han W, Wang W, Mohammed KA, Alpha-defensins SY. Increase lung fibroblast proliferation and collagen synthesis via the beta-catenin signaling pathway. FEBS J. 2009;276(22):6603–14.CrossRefPubMedPubMedCentral
24.
go back to reference Bdeir K, Higazi AA, Kulikovskaya I, Christofidou-Solomidou M, Vinogradov SA, Allen TC, et al. Neutrophil alpha-defensins cause lung injury by disrupting the capillary-epithelial barrier. Am J Respir Crit Care Med. 2010;181(9):935–46.CrossRefPubMedPubMedCentral Bdeir K, Higazi AA, Kulikovskaya I, Christofidou-Solomidou M, Vinogradov SA, Allen TC, et al. Neutrophil alpha-defensins cause lung injury by disrupting the capillary-epithelial barrier. Am J Respir Crit Care Med. 2010;181(9):935–46.CrossRefPubMedPubMedCentral
25.
go back to reference Saini D, Angaswamy N, Tiriveedhi V, Fukami N, Ramachandran S, Hachem R, et al. Synergistic effect of antibodies to human leukocyte antigens and defensins in pathogenesis of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant. 2010;29(12):1330–6.CrossRefPubMedPubMedCentral Saini D, Angaswamy N, Tiriveedhi V, Fukami N, Ramachandran S, Hachem R, et al. Synergistic effect of antibodies to human leukocyte antigens and defensins in pathogenesis of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant. 2010;29(12):1330–6.CrossRefPubMedPubMedCentral
26.
go back to reference Liu CY, Lin HC, Yu CT, Lin SM, Lee KY, Chen HC, et al. The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells. Life Sci. 2007;80(8):749–58.CrossRefPubMed Liu CY, Lin HC, Yu CT, Lin SM, Lee KY, Chen HC, et al. The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells. Life Sci. 2007;80(8):749–58.CrossRefPubMed
27.
go back to reference Nagaoka I, Suzuki K, Murakami T, Niyonsaba F, Tamura H, Hirata M. Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis. Int J Mol Med. 2010;26(6):925–34.CrossRefPubMed Nagaoka I, Suzuki K, Murakami T, Niyonsaba F, Tamura H, Hirata M. Evaluation of the effect of α-defensin human neutrophil peptides on neutrophil apoptosis. Int J Mol Med. 2010;26(6):925–34.CrossRefPubMed
28.
go back to reference Liu X, Chen Q, Shi S, Shi Z, Lin R, Tan L, et al. Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children. Crit Care. 2012;16(3):R91.CrossRefPubMedPubMedCentral Liu X, Chen Q, Shi S, Shi Z, Lin R, Tan L, et al. Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children. Crit Care. 2012;16(3):R91.CrossRefPubMedPubMedCentral
29.
30.
go back to reference Vento G, Lio A, Tirone C, Aurilia C, Tana M, Piras A, et al. Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates. Pediatr Res. 2013;74(1):19–25.CrossRefPubMed Vento G, Lio A, Tirone C, Aurilia C, Tana M, Piras A, et al. Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates. Pediatr Res. 2013;74(1):19–25.CrossRefPubMed
31.
go back to reference Amenomori M, Mukae H, Ishimatsu Y, Sakamoto N, Kakugawa T, Hara A, et al. Differential effects of human neutrophil peptide-1 on growth factor and interleukin-8 production by human lung fibroblasts and epithelial cells. Exp Lung Res. 2010;36(7):411–9.CrossRefPubMed Amenomori M, Mukae H, Ishimatsu Y, Sakamoto N, Kakugawa T, Hara A, et al. Differential effects of human neutrophil peptide-1 on growth factor and interleukin-8 production by human lung fibroblasts and epithelial cells. Exp Lung Res. 2010;36(7):411–9.CrossRefPubMed
32.
go back to reference Lv J, Xiong Y, Li W, Yang W, Zhao L, He R. BLT1 Mediates Bleomycin-Induced Lung Fibrosis Independently of Neutrophils and CD4+ T Cells. J Immunol 2017; 198(4):1673–1684. Lv J, Xiong Y, Li W, Yang W, Zhao L, He R. BLT1 Mediates Bleomycin-Induced Lung Fibrosis Independently of Neutrophils and CD4+ T Cells. J Immunol 2017; 198(4):1673–1684.
33.
go back to reference Xu R, Feng S, Li Z, Fu Y, Yin P, Ai Z, et al. Polymorphism of DEFA in Chinese Han population with IgA nephropathy. Hum Genet. 2014;133(10):1299–309.CrossRefPubMed Xu R, Feng S, Li Z, Fu Y, Yin P, Ai Z, et al. Polymorphism of DEFA in Chinese Han population with IgA nephropathy. Hum Genet. 2014;133(10):1299–309.CrossRefPubMed
34.
go back to reference Chen Q, Hakimi M, Wu S, Jin Y, Cheng B, Wang H, et al. Increased genomic copy number of DEFA1/DEFA3 is associated with susceptibility to severe sepsis in Chinese Han population. Anesthesiology. 2010;112(6):1428–34.CrossRefPubMed Chen Q, Hakimi M, Wu S, Jin Y, Cheng B, Wang H, et al. Increased genomic copy number of DEFA1/DEFA3 is associated with susceptibility to severe sepsis in Chinese Han population. Anesthesiology. 2010;112(6):1428–34.CrossRefPubMed
35.
go back to reference Lehrer RI, Jung G, Ruchala P, Andre S, Gabius HJ, Multivalent LW. Binding of carbohydrates by the human alpha-defensin, HD5. J Immunol. 2009;183(1):480–90.CrossRefPubMed Lehrer RI, Jung G, Ruchala P, Andre S, Gabius HJ, Multivalent LW. Binding of carbohydrates by the human alpha-defensin, HD5. J Immunol. 2009;183(1):480–90.CrossRefPubMed
36.
go back to reference Arnett E, Lehrer RI, Pratikhya P, Lu W, Seveau S. Defensins enable macrophages to inhibit the intracellular proliferation of listeria monocytogenes. Cell Microbiol. 2011;13(4):635–51.CrossRefPubMed Arnett E, Lehrer RI, Pratikhya P, Lu W, Seveau S. Defensins enable macrophages to inhibit the intracellular proliferation of listeria monocytogenes. Cell Microbiol. 2011;13(4):635–51.CrossRefPubMed
37.
go back to reference Ashitani J, Mukae H, Hiratsuka T, Nakazato M, Kumamoto K, Matsukura S. Elevated levels of alpha-defensins in plasma and BAL fluid of patients with active pulmonary tuberculosis. Chest. 2002;121(2):519–26.CrossRefPubMed Ashitani J, Mukae H, Hiratsuka T, Nakazato M, Kumamoto K, Matsukura S. Elevated levels of alpha-defensins in plasma and BAL fluid of patients with active pulmonary tuberculosis. Chest. 2002;121(2):519–26.CrossRefPubMed
Metadata
Title
Plasma levels of alarmin HNPs 1–3 associate with lung dysfunction after cardiac surgery in children
Authors
XiWang Liu
QiXing Chen
YuJia Luo
YaoQin Hu
DengMing Lai
XiaoLe Zhang
XiangHong Zhang
JianGen Yu
XiangMing Fang
Qiang Shu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2017
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-017-0558-4

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