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Biomarkers of Bronchopulmonary Dysplasia

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Bronchopulmonary Dysplasia

Abstract

As the understanding of the pathogenesis of BPD has progressed in recent decades, there has been a focus on the role of inflammation in the pulmonary growth impairment and abnormal vascular development characterized by the “new” BPD. The inflammatory process is often initiated in response to prenatal factors and exacerbated in the postnatal environment by mechanical ventilation, supplemental oxygen, and infection. The measurement of certain molecules involved in the inflammatory process, termed biomarkers, in various compartments (e.g., the serum and pulmonary secretions) of preterm infants has been studied extensively. While the use of biomarkers in the clinical setting is limited, a more comprehensive understanding of their role in the pathogenesis of BPD may provide insights into the identification of infants at the highest risk of developing BPD in addition to developing potential therapeutic strategies to prevent BPD.

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References

  1. Merritt TA, Cochrane CG, Holcomb K, Bohl B, Hallman M, Strayer D, et al. Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia. J Clin Invest. 1983;72(2):656–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dargaville PA, South M, Vervaart P, McDougall PN. Validity of markers of dilution in small volume lung lavage. Am J Respir Crit Care Med. 1999;160:778–84.

    Article  CAS  PubMed  Google Scholar 

  3. Dargaville PA, South M, McDougall PN. Comparison of two methods of diagnostic lung lavage in ventilated infants with lung disease. Am J Respir Crit Care Med. 1999;160:771–7.

    Article  CAS  PubMed  Google Scholar 

  4. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354:610–21.

    Article  CAS  PubMed  Google Scholar 

  5. Whicher JT, Evans SW. Cytokines in disease. Clin Chem. 1990;36:1269–81.

    CAS  PubMed  Google Scholar 

  6. Ozdemir A, Brown MA, Morgan WJ. Markers and mediators of inflammation in neonatal lung disease. Pediatr Pulmonol. 1997;23:292–306.

    Article  CAS  PubMed  Google Scholar 

  7. Truog WE, Ballard PL, Norberg M, et al. Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide. Pediatrics. 2007;119:670–8.

    Article  PubMed  Google Scholar 

  8. Takasaki J, Ogawa Y. Interleukin 8 and granulocyte elastase alpha 1 proteinase inhibitor complex in the tracheobronchial aspirate of infants with chronic lung disease following inter-uterine infection. Acta Paediatr Jpn. 1996;38:132–6.

    Article  CAS  PubMed  Google Scholar 

  9. Groneck P, Speer CP. Interleukin-8 in pulmonary effluent fluid of preterm infants. J Pediatr. 1993;123:839–40.

    Article  CAS  PubMed  Google Scholar 

  10. D’Angio CT, Finkelstein JN, Lomonaco MB, Paxhia A, Wright SA, Baggs RB, et al. Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis. Am J Physiol Lung Cell Mol Physiol. 1997;272:720–30.

    Google Scholar 

  11. De Dooy J, Ieven M, Stevens W, et al. High levels of CXCL8 in tracheal aspirate samples taken at birth are associated with adverse respiratory outcome only in preterm infants younger than 28 weeks gestation. Pediatr Pulmonol. 2007;42:193–203.

    Article  PubMed  Google Scholar 

  12. Kotecha S, Chan B, Azam N, et al. Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 1995;72:F90–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ambalavanan N, Carlo WA, D’Angio CT, McDonald SA, Das A, Schendel D, Thorsen P, Higgins RD, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics. 2009;123(4):1132–41.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lista G, Castoldi F, Fontana P, et al. Lung inflammation in preterm infants with respiratory distress syndrome: effects of ventilation with different tidal volumes. Pediatr Pulmonol. 2006;41:357–63.

    Article  PubMed  Google Scholar 

  15. Munshi UK, Niu JO, Siddiq MM, et al. Elevation of interleukin-8 and interleukin-6 precedes the influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol. 1997;24:331–6.

    Article  CAS  PubMed  Google Scholar 

  16. D’Angio CT, LoMonaco MB, Chaudhry SA, Paxhia A, Ryan RM. Discordant pulmonary proinflammatory cytokine expression during acute hyperoxia in the newborn rabbit. Exp Lung Res. 1999;25(5):443–65.

    Article  PubMed  Google Scholar 

  17. De Paepe ME, Greco D, Mao Q. Angiogenesis-related gene expression profiling in ventilated preterm human lungs. Exp Lung Res. 2010;36(7):399–410.

    Article  PubMed  Google Scholar 

  18. Baier RJ, Loggins J, Kruger TE. Monocyte chemoattractant protein-1 and interleukin-8 are increased in bronchopulmonary dysplasia: relation to isolation of Ureaplasma urealyticum. J Investig Med. 2001;49:362–9.

    Article  CAS  PubMed  Google Scholar 

  19. Baier RJ, Loggins J, Kruger TE. Increased interleukin-8 and monocyte chemoattractant protein-1 concentrations in mechanically ventilated preterm infants with pulmonary hemorrhage. Pediatr Pulmonol. 2002;34:131–7.

    Article  PubMed  Google Scholar 

  20. Baier RJ, Majid A, Parupia H, Loggins J, Kruger TE. CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. Pediatr Pulmonol. 2004;37:137–48.

    Article  PubMed  Google Scholar 

  21. Groneck P, Gotze-Speer B, Oppermann M, et al. Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics. 1994;93:712–8.

    CAS  PubMed  Google Scholar 

  22. Wang JY, Yeh TF, Lin YJ, Chen WY, Lin CH. Early postnatal dexamethasone therapy may lessen lung inflammation in premature infants with respiratory distress syndrome on mechanical ventilation. Pediatr Pulmonol. 1997;23(3):193–7.

    Article  CAS  PubMed  Google Scholar 

  23. Groneck P, Reuss D, Götze-Speer B, Speer CP. Effects of dexamethasone on chemotactic activity and inflammatory mediators in tracheobronchial aspirates of preterm infants at risk for chronic lung disease. J Pediatr. 1993;122(6):938–44.

    Article  CAS  PubMed  Google Scholar 

  24. Kambas K, Chrysanthopoulou A, Kourtzelis I, Skordala M, Mitroulis I, Rafail S, Vradelis S, Sigalas I, Wu YQ, Speletas M, Kolios G, Ritis K. Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dysplasia model by activating the extrinsic coagulation cascade. J Immunol. 2011;186(11):6568–75.

    Article  CAS  PubMed  Google Scholar 

  25. Vozzelli MA, Mason SN, Whorton MH, Auten RL. Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung. Am J Physiol Lung Cell Mol Physiol. 2004;286(3):L488–93.

    Article  CAS  PubMed  Google Scholar 

  26. Gupta GK, Cole CH, Abbasi S, Demissie S, Njinimbam C, Nielsen HC, Colton T, Frantz 3rd ID. Effects of early inhaled beclomethasone therapy on tracheal aspirate inflammatory mediators IL-8 and IL-1ra in ventilated preterm infants at risk for bronchopulmonary dysplasia. Pediatr Pulmonol. 2000;30(4):275–81.

    Article  CAS  PubMed  Google Scholar 

  27. Kim BI, Lee HE, Choi CW, Jo HS, Choi EH, Koh YY, Choi JH. Increase in cord blood soluble E-selectin and tracheal aspirate neutrophils at birth and the development of new bronchopulmonary dysplasia. J Perinat Med. 2004;32(3):282–7.

    PubMed  Google Scholar 

  28. Ballabh P, Kumari J, Krauss AN, Shin JJ, Jain A, Auld PA, Lesser ML, Cunningham-Rundles S. Soluble E-selectin, soluble L-selectin and soluble ICAM-1 in bronchopulmonary dysplasia, and changes with dexamethasone. Pediatrics. 2003;111(3):461–8.

    Article  PubMed  Google Scholar 

  29. Kotecha S, Silverman M, Shaw RJ, Klein N. Soluble L-selectin concentration in bronchoalveolar lavage fluid obtained from infants who develop chronic lung disease of prematurity. Arch Dis Child Fetal Neonatal Ed. 1998;78:F143–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zeb T, Piedboeuf B, Gamache M, Langston C, Welty SE. P-selectin is upregulated early in the course of hyperoxic lung injury in mice. Free Radic Biol Med. 1996;21(4):567–74.

    Article  CAS  PubMed  Google Scholar 

  31. Ramsay PL, Geske RS, Montgomery CA, Welty SE. Increased soluble E-Selectin is associated with lung inflammation, and lung injury in hyperoxia-exposed rats. Toxicol Lett. 1996;87(2–3):157–65.

    Article  CAS  PubMed  Google Scholar 

  32. Chandra A, Enkhbaatar P, Nakano Y, Traber LD, Traber DL. Sepsis: emerging role of nitric oxide and selectins. Clinics (Sao Paulo). 2006;61(1):71–6.

    Article  Google Scholar 

  33. Speer CP. Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med. 2006;11(5):354–62.

    Article  PubMed  Google Scholar 

  34. Jonsson B, Tullus K, Brauner A, et al. Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1997;77:F198–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Patterson AM, Taciak V, Lovchik J, et al. Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants. Pediatr Infect Dis J. 1998;17:321–8.

    Article  CAS  PubMed  Google Scholar 

  36. Cayabyab RG, Jones CA, Kwong KY, et al. Interleukin-1beta in the bronchoalveolar lavage fluid of premature neonates: a marker for maternal chorioamnionitis and predictor of adverse neonatal outcome. J Matern Fetal Neonatal Med. 2003;14:205–11.

    Article  CAS  PubMed  Google Scholar 

  37. Schneibel KR, Fitzpatrick AM, Ping XD, Brown LA, Gauthier TW. Inflammatory mediator patterns in tracheal aspirate and their association with bronchopulmonary dysplasia in very low birth weight neonates. J Perinatol. 2013;33(5):383–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kotecha S, Wilson L, Wangoo A, et al. Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. Pediatr Res. 1996;40:250–6.

    Article  CAS  PubMed  Google Scholar 

  39. Mahieu LM, De Dooy JJ, Ieven MM, et al. Increased levels of tumor necrosis factor-alpha and decreased levels of interleukin-12 p 70 in tracheal aspirates, within 2 hrs after birth, are associated with mortality among ventilated preterm infants. Pediatr Crit Care Med. 2005;6:682–9.

    Article  PubMed  Google Scholar 

  40. Aghai ZH, Saslow JG, Mody K, Eydelman R, Bhat V, Stahl G, Pyon K, Bhandari V. IFN-γ and IP-10 in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia. Pediatr Pulmonol. 2013;48(1):8–13.

    Article  PubMed  Google Scholar 

  41. Kevill KA, Bhandari V, Kettunen M, Leng L, Fan J, Mizue Y, et al. A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome. J Immunol. 2008;180:601–8.

    Article  CAS  PubMed  Google Scholar 

  42. Rice TW, Wheeler AP, Morris PE, et al. Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine Fab for injection (CytoFab) in severe sepsis. Crit Care Med. 2006;34(9):2271–81.

    Article  CAS  PubMed  Google Scholar 

  43. Eichacker PQ, Parent C, Kalil A, et al. Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med. 2002;166(9):1197–205.

    Article  PubMed  Google Scholar 

  44. Nold MF, Mangan NE, Rudloff I, Cho SX, Shariatian N, Samarasinghe TD, et al. Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia. Proc Natl Acad Sci USA. 2013;110(35):14384–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted. Physiol Rev. 2007;87:69–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sweet DG, Curley AE, Chesshyre E, et al. The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease. Acta Paediatr. 2004;93:791–6.

    Article  CAS  PubMed  Google Scholar 

  47. Ekekezie II, Thibeault DW, Simon SD, et al. Low levels of tissue inhibitors of metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop chronic lung disease. Pediatrics. 2004;113:1709–14.

    Article  PubMed  Google Scholar 

  48. Cederqvist K, Sorsa T, Tervahartiala T, et al. Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics. 2001;108:686–92.

    Article  CAS  PubMed  Google Scholar 

  49. Curley AE, Sweet DG, Thornton CM, O'Hara MD, Chesshyre E, Pizzotti J, et al. Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications forantenatal origins of chronic lung disease. Am J Obstet Gynecol. 2003;188(4):871–5.

    Article  CAS  PubMed  Google Scholar 

  50. Curley AE, Sweet DG, MacMahon KJ, O'Connor CM, Halliday HL. Chorioamnionitis increases matrix metalloproteinase-8 concentrations in bronchoalveolar lavage fluid from preterm babies. Arch Dis Child Fetal Neonatal Ed. 2004;89(1):F61–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bruce MC, Schuyler M, Martin RJ, et al. Risk factors for the degradation of lung elastic fibers in the ventilated neonate. Implications for impaired lung development in bronchopulmonary dysplasia. Am Rev Respir Dis. 1992;146:204–12.

    Article  CAS  PubMed  Google Scholar 

  52. Thibeault DW, Mabry SM, Ekekezie II, Truog WE. Lung elastic tissue maturation and perturbations during the evolution of chronic lung disease. Pediatrics. 2000;106:1452–9.

    Article  CAS  PubMed  Google Scholar 

  53. Cederqvist K, Haglund C, Heikkila P, et al. Pulmonary trypsin-2 in the development of bronchopulmonary dysplasia in preterm infants. Pediatrics. 2003;112:570–7.

    Article  PubMed  Google Scholar 

  54. Cederqvist K, Haglund C, Heikkilä P, Hollenberg MD, Karikoski R, Andersson S. High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants. Pediatr Res. 2005;57(6):831–6.

    Article  CAS  PubMed  Google Scholar 

  55. Stiskal JA, Dunn MS, Shennan AT, O'Brien KK, Kelly EN, Koppel RI, et al. alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial. Pediatrics. 1998;101(1 Pt 1):89–94.

    Article  CAS  PubMed  Google Scholar 

  56. Watterberg KL, Carmichael DF, Gerdes JS, Werner S, Backstrom C, Murphy S. Secretory leukocyte protease inhibitor and lung inflammation in developing bronchopulmonary dysplasia. J Pediatr. 1994;125(2):264–9.

    Article  CAS  PubMed  Google Scholar 

  57. Saugstad OD. Oxidative stress in the newborn—a 30-year perspective. Biol Neonate. 2005;88:228–36.

    Article  CAS  PubMed  Google Scholar 

  58. Pitkänen OM, Hallman M, Andersson SM. Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants. J Pediatr. 1990;116(5):760–4.

    Article  PubMed  Google Scholar 

  59. Clement A, Chadelat K, Sardet A, Grimfeld A, Tournier G. Alveolar macrophage status in bronchopulmonary dysplasia. Pediatr Res. 1988;23(5):470–3.

    Article  CAS  PubMed  Google Scholar 

  60. Contreras M, Hariharan N, Lewandoski JR, et al. Bronchoalveolar oxyradical inflammatory elements herald bronchopulmonary dysplasia. Crit Care Med. 1996;24:29–37.

    Article  CAS  PubMed  Google Scholar 

  61. Thompson A, Bhandari V. Pulmonary biomarkers of bronchopulmonary dysplasia. Biomarker Insights. 2008;3:361–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Frank L, Sosenko IR. Development of lung antioxidant enzyme system in late gestation: possible implications for the prematurely born infant. J Pediatr. 1987;110:9–14.

    Article  CAS  PubMed  Google Scholar 

  63. Autor AP, Frank L, Roberts RJ. Developmental characteristics of pulmonary superoxide dismutase: relationship to idiopathic respiratory distress syndrome. Pediatr Res. 1976;10:154–8.

    Article  CAS  PubMed  Google Scholar 

  64. Sunday ME, Yoder BA, Cuttitta F, et al. Bombesin-like peptide mediates lung injury in a baboon model of bronchopulmonary dysplasia. J Clin Invest. 1998;102:584–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cullen A, Van Marter LJ, Allred EN, et al. Urine bombesin-like peptide elevation precedes clinical evidence of bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2002;165:1093–7.

    Article  PubMed  Google Scholar 

  66. Subramaniam M, Sugiyama K, Coy DH, et al. Bombesin-like peptides and mast cell responses: relevance to bronchopulmonary dysplasia? Am J Respir Crit Care Med. 2003;168:601–11.

    Article  PubMed  Google Scholar 

  67. Davis JM, Parad RB, Michele T, Allred E, Price A, Rosenfeld W, North American Recombinant Human CuZnSOD Study Group. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics. 2003;111(3):469–76.

    Article  PubMed  Google Scholar 

  68. Ahola T, Lapatto R, Raivio KO, Selander B, Stigson L, Jonsson B, et al. N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial. J Pediatr. 2003;143:713–9.

    Article  CAS  PubMed  Google Scholar 

  69. Spits H, de Waal Malefyt R. Functional characterization of human IL-10. Int Arch Allergy Immunol. 1992;99:8–15.

    Article  CAS  PubMed  Google Scholar 

  70. Jones CA, Cayabyab RG, Kwong KY, et al. Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns. Pediatr Res. 1996;39:966–75.

    Article  CAS  PubMed  Google Scholar 

  71. Blahnik MJ, Ramanathan R, Riley CR, Minoo P. Lipopolysaccharide-induced tumor necrosis factor-alpha and IL-10 production by lung macrophages from preterm and term neonates. Pediatr Res. 2001;50:726–31.

    Article  CAS  PubMed  Google Scholar 

  72. Beresford MW, Shaw NJ. Detectable IL-8 and IL-10 in bronchoalveolar lavage fluid from preterm infants ventilated for respiratory distress syndrome. Pediatr Res. 2002;52:973–8.

    Article  CAS  PubMed  Google Scholar 

  73. Bernard A, Roels H, Lauwerys R, et al. Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions. Clin Chim Acta. 1992;207:239–49.

    Article  CAS  PubMed  Google Scholar 

  74. Ramsay PL, DeMayo FJ, Hegemier SE, et al. Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;164:155–61.

    Article  CAS  PubMed  Google Scholar 

  75. Zhang ZQ, Huang XM, Lu H. Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review. Eur J Pediatr. 2014;173(1):15–23.

    Article  CAS  PubMed  Google Scholar 

  76. Wolfson MR, Funanage VL, Kirwin SM, Pilon AL, Shashikant BN, Miller TL, Shaffer TH. Recombinant human Clara cell secretory protein treatment increases lung mRNA expression of surfactant proteins and vascular endothelial growth factor in a premature lamb model of respiratory distress syndrome. Am J Perinatol. 2008;25(10):637–45.

    Article  PubMed  Google Scholar 

  77. Levine CR, Gewolb IH, Allen K, Welch RW, Melby JM, Pollack S, et al. The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. Pediatr Res. 2005;58:15–21.

    Article  CAS  PubMed  Google Scholar 

  78. Gross I, Wilson CM, Ingleson LD, et al. The influence of hormones on the biochemical development of fetal rat lung in organ culture. I Estrogen. Biochim Biophys Acta. 1979;575:375–83.

    Article  CAS  PubMed  Google Scholar 

  79. Thebaud B. Angiogenesis in lung development, injury and repair: implications for chronic lung disease of prematurity. Neonatology. 2007;91:291–7.

    Article  PubMed  Google Scholar 

  80. Been JV, Debeer A, van Iwaarden JF, Kloosterboer N, Passos VL, Naulaers G, Zimmermann LJ. Early alterations of growth factor patterns in bronchoalveolar lavage fluid from preterm infants developing bronchopulmonary dysplasia. Pediatr Res. 2010;67(1):83–9.

    Article  CAS  PubMed  Google Scholar 

  81. Bhandari A, Bhandari V. Biomarkers in bronchopulmonary dysplasia. Paediatr Respir Rev. 2013;14(3):173–9.

    PubMed  Google Scholar 

  82. Buckley S, Shi W, Barsky L, Warburton D. TGF-beta signaling promotes survival and repair in rat alveolar epithelial type 2 cells during recovery after hyperoxic injury. Am J Physiol Lung Cell Mol Physiol. 2008;294:L739–48.

    Article  CAS  PubMed  Google Scholar 

  83. Sime PJ, Xing Z, Graham FL, et al. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 1997;100:768–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gauldie J, Galt T, Bonniaud P, Robbins C, Kelly M, Warburton D. Transfer of the active form of transforming growth factor-beta 1 gene to newborn rat lung induces changes consistent with bronchopulmonary dysplasia. Am J Pathol. 2003;163:2575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lecart C, Cayabyab R, Buckley S, et al. Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation. Biol Neonate. 2000;77:217–23.

    Article  CAS  PubMed  Google Scholar 

  86. Fehrholz M, Speer CP, Kunzmann S. Caffeine and rolipram affect Smad signalling and TGF-β1 stimulated CTGF and transgelin expression in lung epithelial cells. PLoS One. 2014;9(5):e97357.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Kramer EL, Deutsch GH, Sartor MA, Hardie WD, Ikegami M, Korfhagen TR, Le Cras TD. Perinatal increases in TGF-{alpha} disrupt the saccular phase of lung morphogenesis and cause remodeling: microarray analysis. Am J Physiol Lung Cell Mol Physiol. 2007;293:L314–27.

    Article  CAS  PubMed  Google Scholar 

  88. Minami S, Iwamoto R, Mekada E. HB-EGF decelerates cell proliferation synergistically with TGFalpha in perinatal distal lung development. Dev Dyn. 2008;237:247–58.

    Article  CAS  PubMed  Google Scholar 

  89. Rehan VK, Torday JS. Lower parathyroid hormone-related protein content of tracheal aspirates in very low birth weight infants who develop bronchopulmonary dysplasia. Pediatr Res. 2006;60(2):216–20.

    Article  CAS  PubMed  Google Scholar 

  90. Cerny L, Torday JS, Rehan VK. Prevention and treatment of bronchopulmonary dysplasia: contemporary status and future outlook. Lung. 2008;186(2):75–89.

    Article  PubMed  Google Scholar 

  91. Wang K, Huang X, Lu H, Zhang Z. A comparison of KL-6 and Clara cell protein as markers for predicting bronchopulmonary dysplasia in preterm infants. Dis Markers. 2014;2014:736536.

    PubMed  PubMed Central  Google Scholar 

  92. Zhu Y, Fu J, You K, Jin L, Wang M, Lu D, Xue X. Changes in pulmonary tissue structure and KL-6/MUC1 expression in a newborn rat model of hyperoxia-induced bronchopulmonary dysplasia. Exp Lung Res. 2013;39(10):417–26.

    Article  CAS  PubMed  Google Scholar 

  93. Bhandari V, Choo-Wing R, Lee CG, et al. Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nat Med. 2006;12(11):1286–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Aghai Z, Faqiri S, Saslow J, Nakhla T, Farhath S, Kumar A, et al. Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation with dexamethasone. J Perinatol. 2008;28:148–55.

    Article  Google Scholar 

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Jackson, W., Laughon, M.M. (2016). Biomarkers of Bronchopulmonary Dysplasia. In: Bhandari, V. (eds) Bronchopulmonary Dysplasia. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-28486-6_7

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