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Anti-inflammatory Agents for the Prevention of Bronchopulmonary Dysplasia

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Bronchopulmonary Dysplasia

Part of the book series: Respiratory Medicine ((RM))

Abstract

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease (CLD) of infancy that significantly affects mortality and morbidity of preterm infants and is a major health-care burden. The multifactorial etiology and complex pathogenesis of BPD makes it challenging to find a treatment for this condition. Inflammation plays a major role in the development of BPD. Here we briefly review the role of inflammation in the pathogenesis of BPD and the current evidence for anti-inflammatory therapeutics against BPD.

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References

  1. Ghanta S, Leeman KT, Christou H. An update on pharmacologic approaches to bronchopulmonary dysplasia. Semin Perinatol. 2013;37(2):115–23.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hilgendorff A, O’reilly MA. Bronchopulmonary dysplasia early changes leading to long-term consequences. Front Med (Lausanne). 2015;2:2.

    Google Scholar 

  3. Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100(3):145–57. doi:10.1002/bdra.23235.

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967;276:357–68.

    Article  PubMed  Google Scholar 

  6. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    Article  CAS  PubMed  Google Scholar 

  7. Parker RA, Lindstrom DP, Cotton RB. Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia. Semin Perinatol. 1996;20:206–9.

    Article  CAS  PubMed  Google Scholar 

  8. Bland R. Neonatal chronic lung disease in the post-surfactant era. Biol Neonate. 2005;88:181–91.

    Article  PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. Mcevoy CT, Jain L, Schmidt B, Abman S, Bancalari E, Aschner JL. Bronchopulmonary dysplasia: NHLBI workshop on the primary prevention of chronic lung diseases. Ann Am Thorac Soc. 2014;11 Suppl 3:S146–53.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wright CJ, Kirpalani H. Targeting inflammation to prevent bronchopulmonary dysplasia: can new insights be translated into therapies? Pediatrics. 2011;128(1):111–26.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shaw GM, O’brodovich HM. Progress in understanding the genetics of bronchopulmonary dysplasia. Semin Perinatol. 2013;37(2):85–93.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hagood JS. Beyond the genome: epigenetic mechanisms in lung remodeling. Physiology (Bethesda). 2014;29(3):177–85.

    CAS  Google Scholar 

  14. Hamvas A, Deterding R, Balch WE, et al. Diffuse lung disease in children: summary of a scientific conference. Pediatr Pulmonol. 2014;49(4):400–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Joss-Moore LA, Wang Y, Ogata EM, Sainz AJ, Yu X, Callaway CW, McKnight RA, Albertine KH, Lane RH. IUGR differentially alters MeCP2 expression and H3K9Me3 of the PPARgamma gene in male and female rat lungs during alveolarization. Birth Defects Res A Clin Mol Teratol. 2011;91:672–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG. 2006;113 Suppl 3:17–42. doi:10.1111/j.1471-0528.2006.01120.x.

    Article  CAS  PubMed  Google Scholar 

  17. Bhandari V. Postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100(3):189–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Russell GA. Antioxidants and neonatal lung disease. Eur J Pediatr. 1994;153(9 Suppl 2):S36–41.

    Article  CAS  PubMed  Google Scholar 

  19. Saugstad OD. Bronchopulmonary dysplasia-oxidative stress and antioxidants. Semin Neonatol. 2003;8(1):39–49.

    Article  PubMed  Google Scholar 

  20. Russell GA, Cooke RW. Randomised controlled trial of allopurinol prophylaxis in very preterm infants. Arch Dis Child Fetal Neonatal Ed. 1995;73:F27–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2012;10:CD004865.

    PubMed  Google Scholar 

  22. 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 

  23. Watts JL, Milner R, Zipursky A, et al. Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. Eur Respir J. 1991;4:188–90.

    CAS  PubMed  Google Scholar 

  24. Rosenfeld WN, Davis JM, Parton L, Richter SE, Price A, Flaster E, et al. Safety and pharmacokinetics of recombinant human superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome. Pediatrics. 1996;97(6 Part 1):811–7.

    CAS  PubMed  Google Scholar 

  25. Davis JM, Parad RB, Michele T, et al. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics. 2003;111:469–76.

    Article  PubMed  Google Scholar 

  26. Pearson E, Bose C, Snidow T, Ransom L, Young T, Bose G, et al. Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia. J Pediatr. 1992;121:420–7.

    Article  CAS  PubMed  Google Scholar 

  27. Kennedy KA, Stoll BJ, Ehrenkranz RA, Oh W, Wright LL, Stevenson DK, et al. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research network. Early Hum Dev. 1997;49:19–31.

    Article  CAS  PubMed  Google Scholar 

  28. Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev. 2011;10:CD000501.

    PubMed  Google Scholar 

  29. Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, et al. Vitamin A supplementation for extremely low birth weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999;340:1962–8. doi:10.1056/NEJM199906243402505.

    Article  CAS  PubMed  Google Scholar 

  30. Poggi C, Dani C. Antioxidant strategies and respiratory disease of the preterm newborn: an update. Oxid Med Cell Longev. 2014;2014:721043.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Ramanathan R. Choosing a right surfactant for respiratory distress syndrome treatment. Neonatology. 2008;95(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  32. Dani C, Buonocore G, Longini M, et al. Superoxide dismutase and catalase activity in naturally derived commercial surfactants. Pediatr Pulmonol. 2009;44(11):1125–31.

    Article  PubMed  Google Scholar 

  33. Matalon S, Wright JR. Surfactant proteins and inflammation: the Yin and the Yang. Am J Respir Cell Mol Biol. 2004;31(6):585–6.

    Article  CAS  PubMed  Google Scholar 

  34. Matalon S, Holm BA, Baker RR, Whitfield MK, Freeman BA. Characterization of antioxidant activities of pulmonary surfactant mixtures. Biochim Biophys Acta. 1990;1035(2):121–7.

    Article  CAS  PubMed  Google Scholar 

  35. Merritt TA, Hallman M, Holcomb K. Human surfactant treatment of severe respiratory distress syndrome: pulmonary effluent indicators of lung inflammation. J Pediatr. 1986;108(5):741–8.

    Article  CAS  PubMed  Google Scholar 

  36. Haagsman HP, Hogenkamp A, Van Eijk M, Veldhuizen EJA. Surfactant collectins and innate immunity. Neonatology. 2008;93(4):288–94.

    Article  PubMed  Google Scholar 

  37. Matalon S, Shrestha K, Kirk M, et al. Modification of surfactant protein D by reactive oxygen-nitrogen intermediates is accompanied by loss of aggregating activity, in vitro and in vivo. FASEB J. 2009;23(5):1415–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wu Y, Adam S, Hamann L, et al. Accumulation of inhibitory κB-α as a mechanism contributing to the anti-inflammatory effects of surfactant protein-A. Am J Respir Cell Mol Biol. 2004;31(6):587–94.

    Article  CAS  PubMed  Google Scholar 

  39. Wofford JA, Wright JR. Surfactant protein A regulates IgG-mediated phagocytosis in inflammatory neutrophils. Am J Physiol Lung Cell Mol Physiol. 2007;293(6):L1437–43.

    Article  CAS  PubMed  Google Scholar 

  40. Kotecha S, Davies PL, Clark HW, McGreal EP. Increased prevalence of low oligomeric state surfactant protein D with restricted lectin activity in bronchoalveolar lavage fluid from preterm infants. Thorax. 2013;68(5):460–7.

    Article  PubMed  Google Scholar 

  41. Soll RF. Synthetic surfactant for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2000;2:CD001149.

    PubMed  Google Scholar 

  42. Soll R, Ozek E. Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2010;1:CD001079.

    PubMed  Google Scholar 

  43. Seger N, Soll R. Animal derived surfactant extract for treatment of respiratory distress syndrome. Cochrane Database Syst Rev. 2009;2:CD007836.

    PubMed  Google Scholar 

  44. Kallapur SG, Jobe AH. Contribution of inflammation to lung injury and development. Arch Dis Child Fetal Neonatal Ed. 2006;91(2):F132–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bancalari E, Claure N, Sosenko IR. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003;8:63–71.

    Article  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. Fanaroff AA, Korones SB, Wright LL, et al. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J. 1998;17(7):593–8.

    Article  CAS  PubMed  Google Scholar 

  48. Stoll BJ, Hansen N, Fanaroff AA, et al. Late onset sepsis in very low birth weight neonates: the experience of the NICHD neonatal research network. Pediatrics. 2002;110(2 pt 1):285–91.

    Article  PubMed  Google Scholar 

  49. Pugin J. Molecular mechanisms of lung cell activation induced by cyclic stretch. Crit Care Med. 2003;31(4 Suppl):S200–6.

    Article  CAS  PubMed  Google Scholar 

  50. Torday JS, Rehan VK. Developmental cell/molecular biologic approach to the etiology and treatment of bronchopulmonary dysplasia. Pediatr Res. 2007;62(1):2–7.

    Article  PubMed  Google Scholar 

  51. Liu Y-Y, Li L-F, Fu J-Y, Kao K-C, Huang C-C, et al. Induced pluripotent stem cell therapy ameliorates hyperoxia-augmented ventilator-induced lung injury through suppressing the Src pathway. PLoS One. 2014;9(10):e109953. doi:10.1371/journal.pone.0109953.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Li LF, Kao KC, Yang CT, Huang CC, Liu YY. Ethyl pyruvate reduces ventilation-induced neutrophil infiltration and oxidative stress. Exp Biol Med (Maywood). 2012;237(6):720–7.

    Article  CAS  Google Scholar 

  53. Li LF, Huang CC, Lin HC, Tsai YH, Quinn DA, Liao SK. Unfractionated heparin and enoxaparin reduce high-stretch ventilation augmented lung injury: a prospective, controlled animal experiment. Crit Care. 2009;13(4):R108.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li LF, Yang CT, Huang CC, Liu YY, Kao KC, Lin HC. Low-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung injury via serine/threonine kinase-protein kinase B. Respir Res. 2011;12:90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007;4:CD003063. pub3.

    Google Scholar 

  56. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2012;3:CD000510.

    PubMed  Google Scholar 

  57. Bhandari V. The potential of non-invasive ventilation to decrease BPD. Semin Perinatol. 2013;37(2):108–14.

    Article  PubMed  Google Scholar 

  58. Meneses J, Bhandari V, Alves JG. Nasal intermittent positive pressure ventilation vs. nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:372–6.

    Article  PubMed  Google Scholar 

  59. Moretti C, Giannini L, Fassi C, Gizzi C, Papoff P, Colarizi P. Nasal flow synchronized intermittent positive pressure ventilation to facilitate weaning in very low birth weight infants: unmasked randomized controlled trial. Pediatr Int. 2008;50:85–91.

    Article  PubMed  Google Scholar 

  60. Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts R. Nasal intermittent positive pressure (NIPPV) does not confer benefit above nasal CPAP (nCPAP) in extremely low birth weight (ELBW)infants <1000 g BW—the NIPPV International Randomized Controlled Trial. EPAS. 2012;1675.1671.

    Google Scholar 

  61. Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks’ gestation: a randomized, controlled trial. J Perinatol. 2012;32:336–43.

    Article  CAS  PubMed  Google Scholar 

  62. Bhandari A, Bhandari V. Pitfalls, problems, and progress in bronchopulmonary dysplasia. Pediatrics. 2009;123(6):1562–73.

    Article  PubMed  Google Scholar 

  63. Cirino G, Distrutti E, Wallace JL. Nitric oxide and inflammation. Inflamm Allergy Drug Targets. 2006;5(2):115–9.

    Article  CAS  PubMed  Google Scholar 

  64. Truog WE, Nelin LD, Das A, et al. Inhaled nitric oxide usage in preterm infants in the NICHD neonatal research network: inter-site variation and propensity evaluation. J Perinatol. 2014;34(11):842–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Askie LM, Ballard RA, Cutter GR, et al. Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials. Pediatrics. 2011;128(4):729–39.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Barrington KJ, Finer N. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2010;12:CD000509.

    PubMed  Google Scholar 

  67. Kinsella JP, Cutter GR, Steinhorn RH, et al. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr. 2014;165(6):1104–8.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, et al. Randomized trial of late surfactant treatment in ventilated preterm infants receiving inhaled nitric oxide. J Pediatr. 2015 Oct 20. pii:S0022-3476(15)01044-6

    Google Scholar 

  69. Aghai ZH, Kode A, Saslow JG, et al. Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants. Pediatr Res. 2007;62(4):483–8.

    Article  CAS  PubMed  Google Scholar 

  70. Ballard HO, Shook LA, Bernard P, et al. Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial. Pediatr Pulmonol. 2011;46(2):111–8.

    Article  PubMed  Google Scholar 

  71. 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.

    Article  CAS  PubMed  Google Scholar 

  72. Viscardi RM, Othman AA, Hassan HE, et al. Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose. Antimicrob Agents Chemother. 2013;57(5):2127–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Schulzke SM, Kaempfen S, Patole SK. Pentoxifylline for the prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2014;11:CD010018.

    PubMed  Google Scholar 

  74. Schulzke SM, Deshmukh M, Nathan EA, Doherty DA, Patole SK. Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates. J Pediatr. 2015;166(5):1158–62.e2.

    Article  CAS  PubMed  Google Scholar 

  75. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;3:CD004454.

    PubMed  Google Scholar 

  76. Crowther CA, Mckinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;6:CD003935.

    PubMed  Google Scholar 

  77. Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;8:CD006764.

    PubMed  Google Scholar 

  78. Doyle LW, Ehrenkranz RA, Halliday HL. Early (<8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014;5:CD001146. pub4.

    PubMed  Google Scholar 

  79. Doyle LW, Ehrenkranz RA, Halliday HL. Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014;5:CD001145.

    PubMed  Google Scholar 

  80. Halliday HL, Ehrenkranz RA, Doyle LW. Early (<8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2010;1:CD001146.

    PubMed  Google Scholar 

  81. Doyle LW, Ehrenkranz RA, Halliday HL. Postnatal hydrocortisone for preventing or treating bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology. 2010;98(2):111–7.

    Article  CAS  PubMed  Google Scholar 

  82. Onland W, Offringa M, van Kaam A. Late (≥ 7 days) inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2012;(4):CD002311. doi:10.1002/14651858.CD002311.pub3.

  83. Shah VS, Ohlsson A, Halliday HL, Dunn M. Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very lowbirth weight preterm neonates. Cochrane Database Syst Rev. 2012;(5):CD001969. doi:10.1002/14651858.CD001969.pub3.

  84. Shah SS, Ohlsson A, Halliday HL, Shah VS. Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev. 2012;(5):CD002058. doi:10.1002/14651858.CD002058.pub2.

  85. Iyengar A, Davis JM. Drug therapy for the prevention and treatment of bronchopulmonary dysplasia. Front Pharmacol. 2015;6:12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, et al. Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med. 2015;373(16):1497–506. doi:10.1056/NEJMoa1501917.

    Article  PubMed  Google Scholar 

  87. Ma L, Li N, Liu X, et al. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice. Nutrition. 2012;28(11–12):1186–91.

    Article  CAS  PubMed  Google Scholar 

  88. Manley BJ, Makrides M, Collins CT, et al. High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics. 2011;128(1):e71–7.

    Article  PubMed  Google Scholar 

  89. O’reilly M, Thébaud B. Using cell-based strategies to break the link between bronchopulmonary dysplasia and the development of chronic lung disease in later life. Pulm Med. 2013;2013:874161.

    PubMed  PubMed Central  Google Scholar 

  90. Fung ME, Thébaud B. Stem cell-based therapy for neonatal lung disease: it is in the juice. Pediatr Res. 2014;75(1–1):2–7.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Chang YS, Ahn SY, Yoo HS, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014;164(5):966–72.e6.

    Article  PubMed  Google Scholar 

  92. Sakurai R, Shin E, Fonseca S, Sakurai T, Litonjua AA, Weiss ST, Torday JS, Rehan VK. 1α,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofibroblast apoptosis. Am J Physiol Lung Cell Mol Physiol. 2009;297:L496–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nguyen TM, Guillozo H, Marin L, Tordet C, Koite S, Garabedian M. Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium. Am J Physiol Lung Cell Mol Physiol. 1996;271:L392–9.

    CAS  Google Scholar 

  94. Lykkedegn S, Sorensen GL, Beck-nielsen SS, Christesen HT. The impact of vitamin D on fetal and neonatal lung maturation. A systematic review. Am J Physiol Lung Cell Mol Physiol. 2015;308(7):L587–602.

    Article  CAS  PubMed  Google Scholar 

  95. Hollis BW, Wagner CL. Vitamin D deficiency during pregnancy: an ongoing epidemic. Am J Clin Nutr. 2006;84(2):273.

    CAS  PubMed  Google Scholar 

  96. Devereux G, Litonjua AA, Turner SW, et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr. 2007;85(3):853–9.

    CAS  PubMed  Google Scholar 

  97. Yurt M, Liu J, Sakurai R, Gong M, Husain SM, Siddiqui MA, Husain M, et al. Vitamin D supplementation blocks pulmonary structural and functional changes in a rat model of perinatal vitamin D deficiency. Am J Physiol Lung Cell Mol Physiol. 2014;307(11):L859–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Torday JS, Torres E, Rehan VK. The role of fibroblast trans differentiation in lung epithelial cell proliferation, differentiation, and repair in vitro. Pediatr Pathol Mol Med. 2003;22:189–207.

    Article  CAS  PubMed  Google Scholar 

  99. Rehan VK, Wang Y, Patel S, Santos J, Torday JS. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, prevents hyperoxia-induced neonatal rat lung injury in vivo. Pediatr Pulmonol. 2006;41(6):558–69.

    Article  PubMed  Google Scholar 

  100. Morales E, Sakurai R, Husain S, et al. Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats. Pediatr Res. 2014;75(5):631–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Rehan VK, Sakurai R, Corral J, et al. Antenatally administered PPAR-gamma agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury. Am J Physiol Lung Cell Mol Physiol. 2010;299(5):L672–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang Y, Santos J, Sakurai R, et al. Peroxisome proliferator-activated receptor gamma agonists enhance lung maturation in a neonatal rat model. Pediatr Res. 2009;65(2):150–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Sakurai R, Li Y, Torday JS, Rehan VK. Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling. Am J Physiol Lung Cell Mol Physiol. 2011;301(5):L721–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Sakurai R, Villarreal P, Husain S, et al. Curcumin protects the developing lung against long-term hyperoxic injury. Am J Physiol Lung Cell Mol Physiol. 2013;305(4):L301–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Zhang Y, Liang D, Dong L, et al. Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury. Respir Res. 2015;16:43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Farrow KN, Steinhorn RH. Sildenafil therapy for bronchopulmonary dysplasia: not quite yet. J Perinatol. 2012;32(1):1–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ladha F, Bonnet S, Eaton F, Hashimoto K, Korbutt G, Thébaud B. Sildenafil improves alveolar growth and pulmonary hypertension in hyperoxia-induced lung injury. Am J Respir Crit Care Med. 2005;172(6):750–6.

    Article  PubMed  Google Scholar 

  108. Rubin LJ, Badesch DB, Fleming TR, Galie N, Simonneau G, Ghofrani HA, et al. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: SUPER-2. Chest. 2011;140(5):1274–83.

    Article  CAS  PubMed  Google Scholar 

  109. De Visser YP, Walther FJ, Laghmani el H, Boersma H, Van der Laarse A, Wagenaar GT. Sildenafil attenuates pulmonary inflammation and fibrin deposition, mortality and right ventricular hypertrophy in neonatal hyperoxic lung injury. Respir Res. 2009;10:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Park HS, Park JW, Kim HJ, et al. Sildenafil alleviates bronchopulmonary dysplasia in neonatal rats by activating the hypoxia-inducible factor signaling pathway. Am J Respir Cell Mol Biol. 2013;48(1):105–13.

    Article  CAS  PubMed  Google Scholar 

  111. Nyp M, Sandritter T, Poppinga N, Simon C, Truog WE. Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits? J Perinatol. 2012;32(1):64–9.

    Article  CAS  PubMed  Google Scholar 

  112. Tan K, Krishnamurthy MB, O’heney JL, Paul E, Sehgal A. Sildenafil therapy in bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective study of efficacy and safety. Eur J Pediatr. 2015;174:1109–15.

    Article  CAS  PubMed  Google Scholar 

  113. Chandra S, Davis JM, Drexler S, et al. Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury. Pediatr Res. 2003;54(4):509–15.

    Article  CAS  PubMed  Google Scholar 

  114. Wolfson MR, Funanage VL, Kirwin SM, et al. 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 

  115. Miller TL, Shashikant BN, Melby JM, Pilon AL, Shaffer TH, Wolfson MR. Recombinant human Clara cell secretory protein in acute lung injury of the rabbit: effect of route of administration. Pediatr Crit Care Med. 2005;6(6):698–706.

    Article  PubMed  Google Scholar 

  116. Levine CR, Gewolb IH, Allen K, 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(1):15–21.

    Article  CAS  PubMed  Google Scholar 

  117. Abdel-latif ME, Osborn DA. Intratracheal Clara cell secretory protein (CCSP) administration in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database Syst Rev. 2011;5:CD008308.

    PubMed  Google Scholar 

  118. Clinical Trials.gov Efficacy of Recombinant Human Clara Cell 10 Protein (rhCC10) Administered to Premature Neonates with Respiratory Distress Syndrome Clinical. Trials.gov identifier: NCT01941745.

    Google Scholar 

  119. Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112–21.

    Article  CAS  PubMed  Google Scholar 

  120. Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M. Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med. 1992;326:1233–9.

    Article  CAS  PubMed  Google Scholar 

  121. Howlett A, Ohlsson A. Inositol for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2003;4:CD000366.

    PubMed  Google Scholar 

  122. Ozdemir R, Erdeve O, Dizdar EA, Oguz SS, Uras N, Saygan S, et al. Clarithromycin in preventing bronchopulmonary dysplasia in urea plasma urealyticum-positive preterm infants. Pediatrics. 2011;128:e1496–501.

    Article  PubMed  Google Scholar 

  123. Beam KS, Aliaga S, Ahlfeld SK, Cohen-Wolkowiez M, Smith PB, Laughon MM. A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants. J Perinatol. 2014;34:705–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Daniels L, Gibson R, Simmer K. Randomised clinical trial of parenteral selenium supplementation in preterm infants. Arch Dis Child. 1996;74:F158–64.

    Article  CAS  Google Scholar 

  125. Darlow BA, Winterbourn CC, Inder TE, Graham PJ, Harding JE, Weston PJ, Austin NC, Elder DE, Mogridge N, Buss IH, Sluis KB, The New Zealand Neonatal Study Group. The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. J Pediatr. 2000;136:473–80.

    Article  CAS  PubMed  Google Scholar 

  126. Huston RK, Jelen BJ, Vidgoff J. Selenium supplementation in low-birthweight premature infants: relationship to trace metals and antioxidant enzymes. J Parent Ent Nutr. 1991;15:556–9.

    Article  CAS  Google Scholar 

  127. Darlow BA, Austin N. Selenium supplementation to prevent short-term morbidity in preterm neonates. Cochrane Database Syst Rev. 2003;(4):CD003312. doi:10.1002/14651858.CD003312.

  128. Trotter A, Maier L, Grill HJ, Kohn T, Heckmann M, Pohlandt F. Effects of postnatal estradiol and progesterone replacement in extremely preterm infants. J Clin Endocrinol Metab. 1999;84:4531–5.

    Article  CAS  PubMed  Google Scholar 

  129. Stiskal JA, Dunn MS, Shennan AT, et al. alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial. Pediatrics. 1998;101:89–94.

    Article  CAS  PubMed  Google Scholar 

  130. Gitto E, Reiter RJ, Amodio A, et al. Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin. J Pineal Res. 2004;36(4):250–5.

    Article  CAS  PubMed  Google Scholar 

  131. Viscardi RM, Hasday JD, Gumpper KF, et al. Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med. 1997;156:1523–9.

    Article  CAS  PubMed  Google Scholar 

  132. Ng GY, Ohlsson A. Cromolyn sodium for the prevention of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2001;1:CD003059.

    Google Scholar 

  133. Watterberg KL, Murphy S. The neonatal cromolyn study group failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. Pediatrics. 1993;91:803–6.

    CAS  PubMed  Google Scholar 

  134. Smith LM, Leake RD, Berman N, et al. Postnatal thyroxine supplementation in infants less than 32 weeks’ gestation: effects on pulmonary morbidity. J Perinatol. 2000;20:427–31.

    Article  CAS  PubMed  Google Scholar 

  135. Terrin G, Canani RB, Passariello A, Messina F, Conti MG, Caoci S, et al. Zinc supplementation reduces morbidity and mortality in very-lowbirth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country. Am J Clin Nutr. 2013;98:1468–74.

    Article  CAS  PubMed  Google Scholar 

  136. Rush MG, Engelhardt B, Parker RA, Hazinski TA. Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia. J Pediatr. 1990;117(1 Pt 1):112–8.

    Article  CAS  PubMed  Google Scholar 

  137. Sahni J, Phelps SJ. Nebulized furosemide in the treatment of bronchopulmonary dysplasia in preterm infants. J Pediatr Pharmacol Ther. 2011;16(1):14–22.

    PubMed  PubMed Central  Google Scholar 

  138. Stewart A, Brion LP. Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2011;9:CD001453.

    PubMed  Google Scholar 

  139. Ng G, Da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2012;6:CD003214.

    PubMed  Google Scholar 

  140. De Boeck K, Smith J, Van Lierde S, Devlieger H. Response to bronchodilators in clinically stable 1-year-old patients with bronchopulmonary dysplasia. Eur J Pediatr. 1998;157(1):75–9.

    Article  PubMed  Google Scholar 

  141. ClinicalTrials.gov The efficacy and safety of montelukast sodium in the prevention of bronchopulmonary dysplasia (BPD). Clinical.Trials.gov identifier: NCT01717625.

    Google Scholar 

  142. Bhandari V. Drug therapy trials for the prevention of bronchopulmonary dysplasia: current and future targets. Front Pediatr. 2014;2:76. doi:10.3389/fped.2014.00076. eCollection 2014.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neonatology, Pediatrics, Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90502, USA

    Sneha Taylor MBBS, MD, FAAP & Virender K. Rehan MD, MRCP (UK), MRCPI (Dublin)

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  1. Sneha Taylor MBBS, MD, FAAP
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  2. Virender K. Rehan MD, MRCP (UK), MRCPI (Dublin)
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Correspondence to Sneha Taylor MBBS, MD, FAAP .

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  1. Department of Neonatology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Vineet Bhandari

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Taylor, S., Rehan, V.K. (2016). Anti-inflammatory Agents for the Prevention of Bronchopulmonary Dysplasia. In: Bhandari, V. (eds) Bronchopulmonary Dysplasia. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-28486-6_18

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