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Pre and Postnatal Inflammation in the Pathogenesis of Bronchopulmonary Dysplasia

  • Kirsten GlaserEmail author
  • Christian P. Speer
Chapter
First Online:
Part of the Respiratory Medicine book series (RM)

Abstract

Pathogenesis of bronchopulmonary dysplasia (BPD) is most likely multifactorial, and involvement of different pathogenetic mechanisms might lead to severe, mild, or moderate disease. BPD is characterized by inflammation, apoptosis, and extensive extracellular matrix remodeling. Pre and postnatal injurious conditions, such as chorioamnionitis, neonatal infection, hyperoxia, hypoxia, or mechanical ventilation have been shown to contribute to the onset and perpetuation of an inflammatory response in the functionally and structurally immature lungs of preterm infants. Perturbation of pro- and anti-inflammatory central signaling pathways and subsequently imbalanced inflammatory responses may lead to aberrant airway-branching and impaired development of epithelial, mesenchymal, and endothelial structures, seriously affecting lung development during a window of vulnerability in genetically susceptible infants. Alterations of normal alveolarization and pulmonary vascular development may result in lifelong impairment of lung function.

Keywords

Preterm infants Bronchopulmonary dysplasia Chorioamnionitis Systemic fetal inflammatory response Inflammation Immaturity Barotrauma Oxygen therapy Window of vulnerability Genetic susceptibility 
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References

  1. 1.
    Philip AG. Bronchopulmonary dysplasia: then and now. Neonatology. 2012;102(1):1–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Reyburn B, Martin RJ, Prakash YS, MacFarlane PM. Mechanisms of injury to the preterm lung and airway: implications for long-term pulmonary outcome. Neonatology. 2012;101(4): 345–52.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Hallman M, Curstedt T, Halliday HL, Saugstad OD, Speer CP. Better neonatal outcomes: oxygen, surfactant and drug delivery. Preface. Neonatology. 2013;103(4):316–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967;276(7): 357–68.PubMedCrossRefGoogle Scholar
  5. 5.
    Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr. 2011;23(2):167–72.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Thebaud B, Abman SH. Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med. 2007;175(10):978–85.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Baker CD, Abman SH. Impaired pulmonary vascular development in bronchopulmonary dysplasia. Neonatology. 2015;107(4):344–51.PubMedCrossRefGoogle Scholar
  8. 8.
    Speer CP. Neonatal respiratory distress syndrome: an inflammatory disease? Neonatology. 2011;99(4):316–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Garcia-Munoz Rodrigo F, Galan Henriquez G, Figueras Aloy J, Garcia-Alix Perez A. Outcomes of very-low-birth-weight infants exposed to maternal clinical chorioamnionitis: a multicentre study. Neonatology. 2014;106(3):229–34.PubMedCrossRefGoogle Scholar
  10. 10.
    Thomas W, Speer CP. Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia—the case in favour. Paediatr Respir Rev. 2014;15(1):49–52.PubMedGoogle Scholar
  11. 11.
    Cullen AB, Cooke PH, Driska SP, Wolfson MR, Shaffer TH. The impact of mechanical ventilation on immature airway smooth muscle: functional, structural, histological, and molecular correlates. Biol Neonate. 2006;90(1):17–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Speer CP. Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology. 2009;95(4):353–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Vogel ER, Britt Jr RD, Trinidad MC, Faksh A, Martin RJ, MacFarlane PM, et al. Perinatal oxygen in the developing lung. Can J Physiol Pharmacol. 2015;93(2):119–27.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Thome U, Gotze-Speer B, Speer CP, Pohlandt F. Comparison of pulmonary inflammatory mediators in preterm infants treated with intermittent positive pressure ventilation or high frequency oscillatory ventilation. Pediatr Res. 1998;44(3):330–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Bose CL, Dammann CE, Laughon MM. Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate. Arch Dis Child Fetal Neonatal Ed. 2008;93(6):F455–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Viscardi RM. Perinatal inflammation and lung injury. Semin Fetal Neonatal Med. 2012;17(1): 30–5.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Speer CP, Gahr M, Wieland M, Eber S. Phagocytosis-associated functions in neonatal monocyte-derived macrophages. Pediatr Res. 1988;24(2):213–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Grigg JM, Savill JS, Sarraf C, Haslett C, Silverman M. Neutrophil apoptosis and clearance from neonatal lungs. Lancet. 1991;338(8769):720–2.PubMedCrossRefGoogle Scholar
  19. 19.
    Kramer BW, Jobe AH, Ikegami M. Monocyte function in preterm, term, and adult sheep. Pediatr Res. 2003;54(1):52–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Nguyen CN, Schnulle PM, Chegini N, Luo X, Koenig JM. Neonatal neutrophils with prolonged survival secrete mediators associated with chronic inflammation. Neonatology. 2010;98(4):341–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Abman SH. Bronchopulmonary dysplasia: “a vascular hypothesis”. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1755–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Ueda K, Cho K, Matsuda T, Okajima S, Uchida M, Kobayashi Y, et al. A rat model for arrest of alveolarization induced by antenatal endotoxin administration. Pediatr Res. 2006;59(3): 396–400.PubMedCrossRefGoogle Scholar
  23. 23.
    Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, et al. Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol. 2012;207(6):475.e1–14.CrossRefGoogle Scholar
  24. 24.
    Nair V, Loganathan P, Soraisham AS. Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis. Neonatology. 2014;106(4):337–47.PubMedCrossRefGoogle Scholar
  25. 25.
    Morley CJ. CPAP and low oxygen saturation for very preterm babies? N Engl J Med. 2010;362(21):2024–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Martin RJ, Fanaroff AA. The preterm lung and airway: past, present, and future. Pediatr Neonatol. 2013;54(4):228–34.PubMedCrossRefGoogle Scholar
  27. 27.
    Manja V, Lakshminrusimha S, Cook DJ. Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis. JAMA Pediatr. 2015;169(4):332–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Saugstad OD. Delivery room management of term and preterm newly born infants. Neonatology. 2015;107(4):365–71.PubMedCrossRefGoogle Scholar
  29. 29.
    Paananen R, Husa AK, Vuolteenaho R, Herva R, Kaukola T, Hallman M. Blood cytokines during the perinatal period in very preterm infants: relationship of inflammatory response and bronchopulmonary dysplasia. J Pediatr. 2009;154(1):39–43.e3.PubMedCrossRefGoogle Scholar
  30. 30.
    Piersigilli F, Bhandari V. Biomarkers in neonatology: the new “omics” of bronchopulmonary dysplasia. J Matern Fetal Neonatal Med. 2015;10:1–7. [Epub ahead of print].Google Scholar
  31. 31.
    Hallman M, Marttila R, Pertile R, Ojaniemi M, Haataja R. Genes and environment in common neonatal lung disease. Neonatology. 2007;91(4):298–302.PubMedCrossRefGoogle Scholar
  32. 32.
    Abman SH, Mourani PM, Sontag M. Bronchopulmonary dysplasia: a genetic disease. Pediatrics. 2008;122(3):658–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Lavoie PM, Dube MP. Genetics of bronchopulmonary dysplasia in the age of genomics. Curr Opin Pediatr. 2010;22(2):134–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Menon R, Taylor RN, Fortunato SJ. Chorioamnionitis—a complex pathophysiologic syndrome. Placenta. 2010;31(2):113–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Combs CA, Gravett M, Garite TJ, Hickok DE, Lapidus J, Porreco R, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1–15.CrossRefGoogle Scholar
  36. 36.
    Onderdonk AB, Delaney ML, DuBois AM, Allred EN, Leviton A, Extremely Low Gestational Age Newborns Study I. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. American Journal of Obstet Gynecol. 2008;198(1):110.e1–7.Google Scholar
  37. 37.
    Speer CP. Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med. 2006;11(5):354–62.PubMedCrossRefGoogle Scholar
  38. 38.
    Goldenberg RL, Andrews WW, Goepfert AR, Faye-Petersen O, Cliver SP, Carlo WA, et al. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol. 2008;198(1):43.e1–5.CrossRefGoogle Scholar
  39. 39.
    Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics. 2009;123(5):1314–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Lee Y, Kim HJ, Choi SJ, Oh SY, Kim JS, Roh CR, et al. Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery. J Perinat Med. 2015;43(2):259–67.PubMedGoogle Scholar
  41. 41.
    DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med. 2012;17(1):2–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Viscardi RM. Ureaplasma species: role in neonatal morbidities and outcomes. Arch Dis Child Fetal Neonatal Ed. 2014;99(1):F87–92.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Lowe J, Watkins WJ, Edwards MO, Spiller OB, Jacqz-Aigrain E, Kotecha SJ, et al. Association between pulmonary ureaplasma colonization and bronchopulmonary dysplasia in preterm infants: updated systematic review and meta-analysis. Pediatr Infect Dis J. 2014;33:697–702.PubMedCrossRefGoogle Scholar
  44. 44.
    Heller DS, Rimpel LH, Skurnick JH. Does histologic chorioamnionitis correspond to clinical chorioamnionitis? J Reprod Med. 2008;53(1):25–8.PubMedGoogle Scholar
  45. 45.
    Been JV, Zimmermann LJ. Histological chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2009;94(3):F218–25.PubMedCrossRefGoogle Scholar
  46. 46.
    Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology. 2011;99(3):177–87.PubMedCrossRefGoogle Scholar
  47. 47.
    Lee J, Oh KJ, Park CW, Park JS, Jun JK, Yoon BH. The presence of funisitis is associated with a decreased risk for the development of neonatal respiratory distress syndrome. Placenta. 2011;32(3):235–40.PubMedCrossRefGoogle Scholar
  48. 48.
    Park CW, Park JS, Jun JK, Yoon BH. Mild to moderate, but not minimal or severe, acute histologic chorioamnionitis or intra-amniotic inflammation is associated with a decrease in respiratory distress syndrome of preterm newborns without fetal growth restriction. Neonatology. 2015;108(2):115–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996;97(2): 210–5.PubMedGoogle Scholar
  50. 50.
    Kramer BW, Kallapur S, Newnham J, Jobe AH. Prenatal inflammation and lung development. Semin Fetal Neonatal Med. 2009;14(1):2–7.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Kramer BW, Ladenburger A, Kunzmann S, Speer CP, Been JV, van Iwaarden JF, et al. Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep. Am J Obstet Gynecol. 2009;200(2):195.e1–10.CrossRefGoogle Scholar
  52. 52.
    Hartling L, Liang Y, Lacaze-Masmonteil T. Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2012;97(1):F8–17.PubMedCrossRefGoogle Scholar
  53. 53.
    Van Marter LJ, Dammann O, Allred EN, Leviton A, Pagano M, Moore M, et al. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr. 2002;140(2):171–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Been JV, Rours IG, Kornelisse RF, Jonkers F, de Krijger RR, Zimmermann LJ. Chorioamnionitis alters the response to surfactant in preterm infants. J Pediatr. 2010;156(1):10–5. e1.PubMedCrossRefGoogle Scholar
  55. 55.
    Inatomi T, Oue S, Ogihara T, Hira S, Hasegawa M, Yamaoka S, et al. Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants. Pediatr Res. 2012;71(3):267–73.PubMedCrossRefGoogle Scholar
  56. 56.
    Prince LS, Dieperink HI, Okoh VO, Fierro-Perez GA, Lallone RL. Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung. Dev Dyn. 2005;233(2):553–61.PubMedCrossRefGoogle Scholar
  57. 57.
    Buhimschi CS, Dulay AT, Abdel-Razeq S, Zhao G, Lee S, Hodgson EJ, et al. Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth. BJOG. 2009;116(2):257–67.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Viscardi RM, Muhumuza CK, Rodriguez A, Fairchild KD, Sun CC, Gross GW, et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. 2004;55(6):1009–17.PubMedCrossRefGoogle Scholar
  59. 59.
    Schmidt B, Cao L, Mackensen-Haen S, Kendziorra H, Klingel K, Speer CP. Chorioamnionitis and inflammation of the fetal lung. Am J Obstet Gynecol. 2001;185(1):173–7.PubMedCrossRefGoogle Scholar
  60. 60.
    May M, Marx A, Seidenspinner S, Speer CP. Apoptosis and proliferation in lungs of human fetuses exposed to chorioamnionitis. Histopathology. 2004;45(3):283–90.PubMedCrossRefGoogle Scholar
  61. 61.
    Kim MA, Lee YS, Seo K. Assessment of predictive markers for placental inflammatory response in preterm births. PLoS One. 2014;9(10):e107880.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011;127(5):817–26.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Bersani I, Speer CP. Nosocomial sepsis in neonatal intensive care: inevitable or preventable? Z Geburtshilfe Neonatol. 2012;216(4):186–90.PubMedCrossRefGoogle Scholar
  64. 64.
    Boghossian NS, Page GP, Bell EF, Stoll BJ, Murray JC, Cotten CM, et al. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr. 2013;162(6):1120–4, 4.e1.Google Scholar
  65. 65.
    Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):F257–63.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Ohlin A, Bjorkman L, Serenius F, Schollin J, Kallen K. Sepsis as a risk factor for neonatal morbidity in extremely preterm infants. Acta Paediatr. 2015;104:1070–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Auriti C, Maccallini A, Di Liso G, Di Ciommo V, Ronchetti MP, Orzalesi M. Risk factors for nosocomial infections in a neonatal intensive-care unit. J Hosp Infect. 2003;53(1):25–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Anderson-Berry A, Brinton B, Lyden E, Faix RG. Risk factors associated with development of persistent coagulase-negative staphylococci bacteremia in the neonate and associated short-term and discharge morbidities. Neonatology. 2011;99(1):23–31.PubMedCrossRefGoogle Scholar
  69. 69.
    Strunk T, Doherty D, Jacques A, Simmer K, Richmond P, Kohan R, et al. Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants. Pediatrics. 2012;129(1):e134–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Ericson JE, Laughon MM. Chorioamnionitis: implications for the neonate. Clin Perinatol. 2015;42(1):155–65. ix.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Bersani I, Thomas W, Speer CP. Chorioamnionitis—the good or the evil for neonatal outcome? J Matern Fetal Neonatal Med. 2012;25 Suppl 1:12–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Hillman NH, Nitsos I, Berry C, Pillow JJ, Kallapur SG, Jobe AH. Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2011;301(5):L712–20.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Copland IB, Martinez F, Kavanagh BP, Engelberts D, McKerlie C, Belik J, et al. High tidal volume ventilation causes different inflammatory responses in newborn versus adult lung. Am J Respir Crit Care Med. 2004;169(6):739–48.PubMedCrossRefGoogle Scholar
  74. 74.
    Backstrom E, Hogmalm A, Lappalainen U, Bry K. Developmental stage is a major determinant of lung injury in a murine model of bronchopulmonary dysplasia. Pediatr Res. 2011;69(4):312–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Network SSGotEKSNNR, Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010;362(21):1970–9.CrossRefGoogle Scholar
  76. 76.
    Roberts CT, Davis PG, Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013? Neonatology. 2013;104(3):203–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Laughon M, Allred EN, Bose C, O'Shea TM, Van Marter LJ, Ehrenkranz RA, et al. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics. 2009;123(4):1124–31.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Kroon AA, Wang J, Huang Z, Cao L, Kuliszewski M, Post M. Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume. Pediatr Res. 2010;68(1):63–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Ricard JD, Dreyfuss D, Saumon G. Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal. Am J Respir Crit Care Med. 2001;163(5):1176–80.PubMedCrossRefGoogle Scholar
  80. 80.
    Bhandari V. Hyperoxia-derived lung damage in preterm infants. Semin Fetal Neonatal Med. 2010;15(4):223–9.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Saugstad OD. Oxidative stress in the newborn—a 30-year perspective. Biol Neonate. 2005;88(3):228–36.PubMedCrossRefGoogle Scholar
  82. 82.
    Wagenaar GT, ter Horst SA, van Gastelen MA, Leijser LM, Mauad T, van der Velden PA, et al. Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress. Free Radic Biol Med. 2004;36(6):782–801.PubMedCrossRefGoogle Scholar
  83. 83.
    Vuichard D, Ganter MT, Schimmer RC, Suter D, Booy C, Reyes L, et al. Hypoxia aggravates lipopolysaccharide-induced lung injury. Clin Exp Immunol. 2005;141(2):248–60.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Urlichs F, Speer CP. Neutrophil function in preterm and term infants. NeoReviews. 2004;5(10):e417–29.CrossRefGoogle Scholar
  85. 85.
    Ogden BE, Murphy SA, Saunders GC, Pathak D, Johnson JD. Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. Am Rev Respir Dis. 1984;130(5):817–21.PubMedGoogle Scholar
  86. 86.
    Groneck P, Gotze-Speer B, Oppermann M, Eiffert H, Speer CP. 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(5):712–8.PubMedGoogle Scholar
  87. 87.
    Merritt TA, Stuard ID, Puccia J, Wood B, Edwards DK, Finkelstein J, et al. Newborn tracheal aspirate cytology: classification during respiratory distress syndrome and bronchopulmonary dysplasia. J Pediatr. 1981;98(6):949–56.PubMedCrossRefGoogle Scholar
  88. 88.
    Nupponen I, Pesonen E, Andersson S, Makela A, Turunen R, Kautiainen H, et al. Neutrophil activation in preterm infants who have respiratory distress syndrome. Pediatrics. 2002;110(1 Pt 1):36–41.PubMedCrossRefGoogle Scholar
  89. 89.
    Jaarsma AS, Braaksma MA, Geven WB, van Oeveren W, Bambang Oetomo S. Activation of the inflammatory reaction within minutes after birth in ventilated preterm lambs with neonatal respiratory distress syndrome. Biol Neonate. 2004;86(1):1–5.PubMedCrossRefGoogle Scholar
  90. 90.
    Turunen R, Nupponen I, Siitonen S, Repo H, Andersson S. Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics. 2006;117(2):448–54.PubMedCrossRefGoogle Scholar
  91. 91.
    Wang L, Scabilloni JF, Antonini JM, Rojanasakul Y, Castranova V, Mercer RR. Induction of secondary apoptosis, inflammation, and lung fibrosis after intratracheal instillation of apoptotic cells in rats. Am J Physiol Lung Cell Mol Physiol. 2006;290(4):L695–702.PubMedCrossRefGoogle Scholar
  92. 92.
    Murch SH, Costeloe K, Klein NJ, MacDonald TT. Early production of macrophage inflammatory protein-1 alpha occurs in respiratory distress syndrome and is associated with poor outcome. Pediatr Res. 1996;40(3):490–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Bhattacharya S, Go D, Krenitsky DL, Huyck HL, Solleti SK, Lunger VA, et al. Genome-wide transcriptional profiling reveals connective tissue mast cell accumulation in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2012;186(4):349–58.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Rosen D, Lee JH, Cuttitta F, Rafiqi F, Degan S, Sunday ME. Accelerated thymic maturation and autoreactive T cells in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2006;174(1):75–83.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Sarelius IH, Glading AJ. Control of vascular permeability by adhesion molecules. Tissue Barriers. 2015;3(1–2):e985954.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    D’Alquen D, Kramer BW, Seidenspinner S, Marx A, Berg D, Groneck P, et al. Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis. Pediatr Res. 2005;57(2):263–9.PubMedCrossRefGoogle Scholar
  97. 97.
    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(2):137–48.PubMedCrossRefGoogle Scholar
  98. 98.
    Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity. 2012;36(5):705–16.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Garcia-Ramallo E, Marques T, Prats N, Beleta J, Kunkel SL, Godessart N. Resident cell chemokine expression serves as the major mechanism for leukocyte recruitment during local inflammation. J Immunol. 2002;169(11):6467–73.PubMedCrossRefGoogle Scholar
  100. 100.
    Smith RE. Chemotactic cytokines mediate leukocyte recruitment in fibrotic lung disease. Biol Signals. 1996;5(4):223–31.PubMedCrossRefGoogle Scholar
  101. 101.
    Yi M, Jankov RP, Belcastro R, Humes D, Copland I, Shek S, et al. Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat. Am J Respir Crit Care Med. 2004;170(11):1188–96.PubMedCrossRefGoogle Scholar
  102. 102.
    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 Invest Med. 2001;49(4):362–9.CrossRefGoogle Scholar
  103. 103.
    Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F, et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1997;177(4): 825–30.PubMedCrossRefGoogle Scholar
  104. 104.
    Bry K, Whitsett JA, Lappalainen U. IL-1beta disrupts postnatal lung morphogenesis in the mouse. Am J Respir Cell Mol Biol. 2007;36(1):32–42.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Hogmalm A, Bry M, Strandvik B, Bry K. IL-1beta expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice. Am J Physiol Lung Cell Mol Physiol. 2014;306(1):L23–34.PubMedCrossRefGoogle Scholar
  106. 106.
    Murch SH, Costeloe K, Klein NJ, Rees H, McIntosh N, Keeling JW, et al. Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome. Pediatr Res. 1996;40(3):484–9.PubMedCrossRefGoogle Scholar
  107. 107.
    Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J. Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest. 2001;107(12):1529–36.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Blackwell TS, Hipps AN, Yamamoto Y, Han W, Barham WJ, Ostrowski MC, et al. NF-kappaB signaling in fetal lung macrophages disrupts airway morphogenesis. J Immunol. 2011;187(5):2740–7.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Cao L, Liu C, Cai B, Jia X, Kang L, Speer CP, et al. Nuclear factor-kappa B expression in alveolar macrophages of mechanically ventilated neonates with respiratory distress syndrome. Biol Neonate. 2004;86(2):116–23.PubMedCrossRefGoogle Scholar
  110. 110.
    Cheah FC, Winterbourn CC, Darlow BA, Mocatta TJ, Vissers MC. Nuclear factor kappaB activation in pulmonary leukocytes from infants with hyaline membrane disease: associations with chorioamnionitis and Ureaplasma urealyticum colonization. Pediatr Res. 2005;57(5 Pt 1):616–23.PubMedCrossRefGoogle Scholar
  111. 111.
    Iosef C, Alastalo TP, Hou Y, Chen C, Adams ES, Lyu SC, et al. Inhibiting NF-kappaB in the developing lung disrupts angiogenesis and alveolarization. Am J Physiol Lung Cell Mol Physiol. 2012;302(10):L1023–36.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Jones CA, Cayabyab RG, Kwong KY, Stotts C, Wong B, Hamdan H, 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(6):966–75.PubMedCrossRefGoogle Scholar
  113. 113.
    Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21(5):331–44.PubMedCrossRefGoogle Scholar
  114. 114.
    Kwong KY, Jones CA, Cayabyab R, Lecart C, Khuu N, Rhandhawa I, et al. The effects of IL-10 on proinflammatory cytokine expression (IL-1beta and IL-8) in hyaline membrane disease (HMD). Clin Immunol Immunopathol. 1998;88(1):105–13.PubMedCrossRefGoogle Scholar
  115. 115.
    Davidson D, Miskolci V, Clark DC, Dolmaian G, Vancurova I. Interleukin-10 production after pro-inflammatory stimulation of neutrophils and monocytic cells of the newborn. Comparison to exogenous interleukin-10 and dexamethasone levels needed to inhibit chemokine release. Neonatology. 2007;92(2):127–33.PubMedCrossRefGoogle Scholar
  116. 116.
    Narimanbekov IO, Rozycki HJ. Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. Exp Lung Res. 1995;21(2):239–54.PubMedCrossRefGoogle Scholar
  117. 117.
    Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6): 805–20.PubMedCrossRefGoogle Scholar
  118. 118.
    Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449(7164):819–26.PubMedCrossRefGoogle Scholar
  119. 119.
    Akira S. TLR signaling. Curr Top Microbiol Immunol. 2006;311:1–16.PubMedGoogle Scholar
  120. 120.
    Glaser K, Speer CP. Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning. Expert Rev Clin Immunol. 2013;9(12):1239–52.PubMedCrossRefGoogle Scholar
  121. 121.
    O’Hare FM, William Watson R, Molloy EJ. Toll-like receptors in neonatal sepsis. Acta Paediatr. 2013;102(6):572–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Kemp MW. Preterm birth, intrauterine infection, and fetal inflammation. Front Immunol. 2014;5:574.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.PubMedCrossRefGoogle Scholar
  124. 124.
    Lee CC, Avalos AM, Ploegh HL. Accessory molecules for Toll-like receptors and their function. Nat Rev Immunol. 2012;12(3):168–79.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Yamamoto M, Takeda K. Current views of toll-like receptor signaling pathways. Gastroenterol Res Pract. 2010;2010:240365.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Jenkins KA, Mansell A. TIR-containing adaptors in Toll-like receptor signalling. Cytokine. 2010;49(3):237–44.PubMedCrossRefGoogle Scholar
  127. 127.
    Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, et al. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell. 1998;2(2):253–8.PubMedCrossRefGoogle Scholar
  128. 128.
    Harju K, Glumoff V, Hallman M. Ontogeny of Toll-like receptors Tlr2 and Tlr4 in mice. Pediatr Res. 2001;49(1):81–3.PubMedCrossRefGoogle Scholar
  129. 129.
    Hillman NH, Moss TJ, Nitsos I, Kramer BW, Bachurski CJ, Ikegami M, et al. Toll-like receptors and agonist responses in the developing fetal sheep lung. Pediatr Res. 2008;63(4):388–93.PubMedCrossRefGoogle Scholar
  130. 130.
    Zhang J, Zhou J, Xu B, Chen C, Shi W. Different expressions of TLRs and related factors in peripheral blood of preterm infants. Int J Clin Exp Med. 2015;8(3):4108–14.PubMedPubMedCentralGoogle Scholar
  131. 131.
    Kramer BW, Kramer S, Ikegami M, Jobe AH. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol. 2002;283(2):L452–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Harju K, Ojaniemi M, Rounioja S, Glumoff V, Paananen R, Vuolteenaho R, et al. Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period. Pediatr Res. 2005;57(5 Pt 1):644–8.PubMedCrossRefGoogle Scholar
  133. 133.
    Contrino J, Krause PJ, Slover N, Kreutzer D. Elevated interleukin-1 expression in human neonatal neutrophils. Pediatr Res. 1993;34(3):249–52.PubMedCrossRefGoogle Scholar
  134. 134.
    Kollmann TR, Levy O, Montgomery RR, Goriely S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity. 2012;37(5):771–83.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem. 1999;274(27): 19403–10.PubMedCrossRefGoogle Scholar
  136. 136.
    Nguyen HA, Rajaram MV, Meyer DA, Schlesinger LS. Pulmonary surfactant protein A and surfactant lipids upregulate IRAK-M, a negative regulator of TLR-mediated inflammation in human macrophages. Am J Physiol Lung Cell Mol Physiol. 2012;303(7):L608–16.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Wu YZ, Medjane S, Chabot S, Kubrusly FS, Raw I, Chignard M, et al. Surfactant protein-A and phosphatidylglycerol suppress type IIA phospholipase A2 synthesis via nuclear factor-kappaB. Am J Respir Crit Care Med. 2003;168(6):692–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Raychaudhuri B, Abraham S, Bonfield TL, Malur A, Deb A, DiDonato JA, et al. Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages. Am J Respir Cell Mol Biol. 2004;30(2):228–32.PubMedCrossRefGoogle Scholar
  139. 139.
    Kerecman J, Mustafa SB, Vasquez MM, Dixon PS, Castro R. Immunosuppressive properties of surfactant in alveolar macrophage NR8383. Inflamm Res. 2008;57(3):118–25.PubMedCrossRefGoogle Scholar
  140. 140.
    Bersani I, Kunzmann S, Speer CP. Immunomodulatory properties of surfactant preparations. Expert Rev Anti Infect Ther. 2013;11(1):99–110.PubMedCrossRefGoogle Scholar
  141. 141.
    Gerber CE, Bruchelt G, Stegmann H, Schweinsberg F, Speer CP. Presence of bleomycin-detectable free iron in the alveolar system of preterm infants. Biochem Biophys Res Commun. 1999;257(1):218–22.PubMedCrossRefGoogle Scholar
  142. 142.
    Speer CP, Ruess D, Harms K, Herting E, Gefeller O. Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. Pediatrics. 1993;91(4):794–9.PubMedGoogle Scholar
  143. 143.
    Altiok O, Yasumatsu R, Bingol-Karakoc G, Riese RJ, Stahlman MT, Dwyer W, et al. Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2006;173(3):318–26.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Speer CP, Pabst MJ, Hedegaard HB, Rest RF, Johnston Jr RB. Enhanced release of oxygen metabolites by monocyte-derived macrophages exposed to proteolytic enzymes: activity of neutrophil elastase and cathepsin G. J Immunol. 1984;133(4):2151–6.PubMedGoogle Scholar
  145. 145.
    Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P, et al. Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics. 2001;108(3):686–92.PubMedCrossRefGoogle Scholar
  146. 146.
    Chetty A, Cao GJ, Severgnini M, Simon A, Warburton R, Nielsen HC. Role of matrix metalloprotease-9 in hyperoxic injury in developing lung. Am J Physiol Lung Cell Mol Physiol. 2008;295(4):L584–92.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Lukkarinen H, Hogmalm A, Lappalainen U, Bry K. Matrix metalloproteinase-9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol. 2009;41(1):59–68.PubMedCrossRefGoogle Scholar
  148. 148.
    Sampath V, Garland JS, Helbling D, Dimmock D, Mulrooney NP, Simpson PM, et al. Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants. Pediatr Res. 2015;77(3):477–83.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Speer CP. Pulmonary inflammation and bronchopulmonary dysplasia. J Perinatol. 2006;26 Suppl 1:S57–62. discussion S3–4.PubMedCrossRefGoogle Scholar
  150. 150.
    Adams EW, Harrison MC, Counsell SJ, Allsop JM, Kennea NL, Hajnal JV, et al. Increased lung water and tissue damage in bronchopulmonary dysplasia. J Pediatr. 2004;145(4):503–7.PubMedCrossRefGoogle Scholar
  151. 151.
    Kramer BW, Moss TJ, Willet KE, Newnham JP, Sly PD, Kallapur SG, et al. Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med. 2001;164(6):982–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Yoder BA, Coalson JJ, Winter VT, Siler-Khodr T, Duffy LB, Cassell GH. Effects of antenatal colonization with ureaplasma urealyticum on pulmonary disease in the immature baboon. Pediatr Res. 2003;54(6):797–807.PubMedCrossRefGoogle Scholar
  153. 153.
    Kallapur SG, Jobe AH, Ikegami M, Bachurski CJ. Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung. Am J Respir Crit Care Med. 2003;167(5): 779–86.PubMedCrossRefGoogle Scholar
  154. 154.
    Miller JD, Benjamin JT, Kelly DR, Frank DB, Prince LS. Chorioamnionitis stimulates angiogenesis in saccular stage fetal lungs via CC chemokines. Am J Physiol Lung Cell Mol Physiol. 2010;298(5):L637–45.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Varughese R, Nayak JL, LoMonaco M, O'Reilly MA, Ryan RM, D'Angio CT. Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs. Lung. 2003;181(6):335–46.PubMedCrossRefGoogle Scholar
  156. 156.
    Wilson MR, Choudhury S, Takata M. Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice. Am J Physiol Lung Cell Mol Physiol. 2005;288(4):L599–607.PubMedCrossRefGoogle Scholar
  157. 157.
    Brew N, Hooper SB, Allison BJ, Wallace MJ, Harding R. Injury and repair in the very immature lung following brief mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2011;301(6):L917–26.PubMedCrossRefGoogle Scholar
  158. 158.
    Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease. Chest. 2004;125(2):754–65.PubMedCrossRefGoogle Scholar
  159. 159.
    Kuang PP, Zhang XH, Rich CB, Foster JA, Subramanian M, Goldstein RH. Activation of elastin transcription by transforming growth factor-beta in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2007;292(4):L944–52.PubMedCrossRefGoogle Scholar
  160. 160.
    Zhao Y, Gilmore BJ, Young SL. Expression of transforming growth factor-beta receptors during hyperoxia-induced lung injury and repair. Am J Physiol. 1997;273(2 Pt 1):L355–62.PubMedGoogle Scholar
  161. 161.
    Hines EA, Sun X. Tissue crosstalk in lung development. J Cell Biochem. 2014;115(9): 1469–77.PubMedCrossRefGoogle Scholar
  162. 162.
    Kunig AM, Balasubramaniam V, Markham NE, Seedorf G, Gien J, Abman SH. Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2006;291(5):L1068–78.PubMedCrossRefGoogle Scholar
  163. 163.
    Bhandari V, Elias JA. Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Free Radic Biol Med. 2006;41(1):4–18.PubMedCrossRefGoogle Scholar
  164. 164.
    D'Angio CT, Maniscalco WM. The role of vascular growth factors in hyperoxia-induced injury to the developing lung. Front Biosci. 2002;7:d1609–23.PubMedCrossRefGoogle Scholar
  165. 165.
    Thebaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F, et al. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation. 2005;112(16):2477–86.PubMedCrossRefGoogle Scholar
  166. 166.
    Thomas W, Seidenspinner S, Kawczynska-Leda N, Kramer BW, Chmielnicka-Kopaczyk M, Marx A, et al. Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants. Am J Obstet Gynecol. 2008;198(1):64.e1–6.CrossRefGoogle Scholar
  167. 167.
    Kunzmann S, Seher A, Kramer BW, Schenk R, Schutze N, Jakob F, et al. Connective tissue growth factor does not affect transforming growth factor-beta 1-induced Smad3 phosphorylation and T lymphocyte proliferation inhibition. Int Arch Allergy Immunol. 2008;147(2):152–60.PubMedCrossRefGoogle Scholar
  168. 168.
    Danan C, Franco ML, Jarreau PH, Dassieu G, Chailley-Heu B, Bourbon J, et al. High concentrations of keratinocyte growth factor in airways of premature infants predicted absence of bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2002;165(10):1384–7.PubMedCrossRefGoogle Scholar
  169. 169.
    Lassus P, Heikkila P, Andersson LC, von Boguslawski K, Andersson S. Lower concentration of pulmonary hepatocyte growth factor is associated with more severe lung disease in preterm infants. J Pediatr. 2003;143(2):199–202.PubMedCrossRefGoogle Scholar
  170. 170.
    Huusko JM, Karjalainen MK, Mahlman M, Haataja R, Kari MA, Andersson S, et al. A study of genes encoding cytokines (IL6, IL10, TNF), cytokine receptors (IL6R, IL6ST), and glucocorticoid receptor (NR3C1) and susceptibility to bronchopulmonary dysplasia. BMC Med Genet. 2014;15:120.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Genc MR, Onderdonk A. Endogenous bacterial flora in pregnant women and the influence of maternal genetic variation. BJOG. 2011;118(2):154–63.PubMedCrossRefGoogle Scholar
  172. 172.
    Strassberg SS, Cristea IA, Qian D, Parton LA. Single nucleotide polymorphisms of tumor necrosis factor-alpha and the susceptibility to bronchopulmonary dysplasia. Pediatr Pulmonol. 2007;42(1):29–36.PubMedCrossRefGoogle Scholar
  173. 173.
    Miller TL, Shashikant BN, Pilon AL, Pierce RA, Shaffer TH, Wolfson MR. Effects of an intratracheally delivered anti-inflammatory protein (rhCC10) on physiological and lung structural indices in a juvenile model of acute lung injury. Biol Neonate. 2006;89(3): 159–70.PubMedCrossRefGoogle Scholar
  174. 174.
    Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014;164(5): 966–72.e6.PubMedCrossRefGoogle Scholar
  175. 175.
    O’Reilly M, Thebaud B. Stem cells for the prevention of neonatal lung disease. Neonatology. 2015;107(4):360–4.PubMedCrossRefGoogle Scholar
  176. 176.
    Pawelec K, Gladysz D, Demkow U, Boruczkowski D. Stem cell experiments moves into clinic: new hope for children with bronchopulmonary dysplasia. Adv Exp Med Biol. 2015;839:47–53.PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.University Children’s Hospital, University of WürzburgWürzburgGermany

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