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Bronchopulmonary Dysplasia and Oxidative Stress in the Newborn

  • Serafina Perrone
  • Elisa Laschi
  • Elisabetta Grande
  • Giuseppe Buonocore
Chapter

Abstract

Bronchopulmonary dysplasia (BPD) is a major cause of respiratory morbidity in preterm infants. The “new BPD” is the form currently observed in very preterm infants, related to disrupted and impaired lung development, and characterized by decreased alveolarization and impaired capillary development. Prematurity, oxygen toxicity, inflammation, mechanical ventilation, and surfactant deficiency are major determinants for BPD pathogenesis. Oxidative stress (OS) and inflammation are strictly interrelated originating a vicious circle that self-amplifies and ultimately leads to the damage of the immature lung. This chapter focuses on the role of OS on the lung injury and analyzes the most recent biomarkers in clinical studies. The comprehension of molecular basis of BPD is crucial for expanding the current possibilities for prevention and treatment and discovering new strategies for this condition.

Keywords

Bronchopulmonary dysplasia Oxidative stress Inflammation Lung 

Notes

Acknowledgments

This study was supported by EURAIBI (EURope Against Infant Brain Injury) Onlus Foundation.

References

  1. Ambalavanan N, Carlo WA, D’Angio CT, McDonald SA, Das A, Schendel D, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network et al (2009) Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics 123:1132–1141.  https://doi.org/10.1542/peds.2008-0526CrossRefPubMedPubMedCentralGoogle Scholar
  2. Astorga CR, González-Candia A, Candia AA, Figueroa EG, Cañas D, Ebensperger G et al (2018) Melatonin decreases pulmonary vascular remodeling and oxygen sensitivity in pulmonary hypertensive newborn lambs. Front Physiol 9:185.  https://doi.org/10.3389/fphys.2018.00185CrossRefPubMedPubMedCentralGoogle Scholar
  3. Auten RL, O’Reilly MA, Oury TD, Nozik-Grayck E, Whorton MH (2006) Transgenic extracellular superoxide dismutase protects postnatal alveolar epithelial proliferation and development during hyperoxia. Am J Physiol Lung Cell Mol Physiol 290:L32–L40.  https://doi.org/10.1152/ajplung.00133.2005CrossRefPubMedGoogle Scholar
  4. Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, NEUROSIS Trial Group et al (2015) Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med 373:1497–1506.  https://doi.org/10.1056/NEJMoa1501917CrossRefPubMedGoogle Scholar
  5. Bassler D, Shinwell ES, Hallman M, Jarreau PH, Plavka R, Carnielli V, Neonatal European Study of Inhaled Steroids Trial Group et al (2018) Long-term effects of inhaled budesonide for bronchopulmonary dysplasia. N Engl J Med 378:148–157.  https://doi.org/10.1056/NEJMoa1708831CrossRefPubMedGoogle Scholar
  6. Carnesecchi S, Deffert C, Pagano A, Garrido-Urbani S, Métrailler-Ruchonnet I, Schäppi M et al (2009) NADPH oxidase-1 plays a crucial role in hyperoxia-induced acute lung injury in mice. Am J Respir Crit Care Med 180:972–981.  https://doi.org/10.1164/rccm.200902-0296OCCrossRefPubMedPubMedCentralGoogle Scholar
  7. D’Angio CT, Ambalavanan N, Carlo WA, McDonald SA, Skogstrand K, Hougaard DM, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network et al (2016) Blood cytokine profiles associated with distinct patterns of bronchopulmonary dysplasia among extremely low birth weight infants. J Pediatr 174:45–51.  https://doi.org/10.1016/j.jpeds.2016.03.058CrossRefPubMedPubMedCentralGoogle Scholar
  8. Darlow BA, Graham PJ, Rojas-Reyes MX (2016) Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev (8):CD000501.  https://doi.org/10.1002/14651858.CD000501.pub4
  9. Datta A, Kim GA, Taylor JM, Gugino SF, Farrow KN, Schumacker PT, Berkelhamer SK (2015) Mouse lung development and NOX1 induction during hyperoxia are developmentally regulated and mitochondrial ROS dependent. Am J Physiol Lung Cell Mol Physiol 309:L369–L377.  https://doi.org/10.1152/ajplung.00176.2014CrossRefPubMedPubMedCentralGoogle Scholar
  10. Delaney C, Wright RH, Tang JR, Woods C, Villegas L, Sherlock L et al (2015) Lack of EC-SOD worsens alveolar and vascular development in a neonatal mouse model of bleomycin-induced bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res 78:634–640.  https://doi.org/10.1038/pr.2015.166CrossRefPubMedPubMedCentralGoogle Scholar
  11. Fabiano A, Gavilanes AW, Zimmermann LJ, Kramer BW, Paolillo P, Livolti G et al (2016) The development of lung biochemical monitoring can play a key role in the early prediction of bronchopulmonary dysplasia. Acta Paediatr 105:535–541. https://doi.org/10.11117apa.13233CrossRefGoogle Scholar
  12. Freund-Michel V, Guibert C, Dubois M, Courtois A, Marthan R, Savineau JP et al (2013) Reactive oxygen species as therapeutic targets in pulmonary hypertension. Ther Adv Resp Dis 7:175–200.  https://doi.org/10.1177/1753465812472940CrossRefGoogle Scholar
  13. Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P et al (2001) Effects of melatonin treatment in septic newborns. Pediatr Res 50:756–760.  https://doi.org/10.1203/00006450-200112000-00021CrossRefPubMedGoogle Scholar
  14. Gitto E, Reiter RJ, Amodio A, Romeo C, Cuzzocrea S, Sabatino G et al (2004) Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin. J Pineal Res 36:250–255.  https://doi.org/10.1111/j.1600-079X.2004.00124.xCrossRefPubMedGoogle Scholar
  15. Gitto E, Marseglia L, Manti S, D’Angelo G, Barberi I, Salpietro C et al (2013) Protective role of melatonin in neonatal disease. Oxidative Med Cell Longev 2013:980374.  https://doi.org/10.1155/2013/980374CrossRefGoogle Scholar
  16. Giusti B, Vestrini A, Poggi C, Magi A, Pasquini E, Abbate R et al (2012) Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants. Free Radic Res 46:1130–1139.  https://doi.org/10.3109/10715762.2012.692787CrossRefPubMedGoogle Scholar
  17. Hines D, Modi N, Lee SK, Isayama T, Sjӧrs G, Gagliardi L, International Network for Evaluating Outcomes (iNEO) of Neonates et al (2017) Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus. Acta Paediatr 106:366–374.  https://doi.org/10.1111/apa.13672CrossRefPubMedGoogle Scholar
  18. Hsiao CC, Chang JC, Tsao LY, Yang RC, Chen HN, Lee CH et al (2017) Correlates of elevated Interleukin-6 and 8-Hydroxy-2′-Deoxyguanosine levels in tracheal aspirates from very low birth weight infants who develop bronchopulmonary dysplasia. Pediatr Neonatol 58:63–69.  https://doi.org/10.1016/j.pedneo.2016.01.004CrossRefPubMedGoogle Scholar
  19. Iyengar A, Davis JM (2015) Drug therapy for the prevention and treatment of bronchopulmonary dysplasia. Front Pharmacol 6:12.  https://doi.org/10.3389/fphar.2015.00012CrossRefPubMedPubMedCentralGoogle Scholar
  20. James ML, Ross AC, Bulger A, Philips JB 3rd, Ambalavanan N (2010) Vitamin A and retinoic acid act synergistically to increase lung retinyl esters during normoxia and reduce hyperoxic lung injury in newborn mice. Pediatr Res 67:591–597.  https://doi.org/10.1203/PDR.0b013e3181dbac3dCrossRefPubMedPubMedCentralGoogle Scholar
  21. Jensen EA, Schmidt B (2014) Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol 100:145–157.  https://doi.org/10.1002/bdra.23235CrossRefPubMedGoogle Scholar
  22. Jensen EA, Wright CJ (2018) Bronchopulmonary dysplasia: the ongoing search for one definition to rule them all. J Pediatr 197:8–10.  https://doi.org/10.1016/j.jpeds.2018.02.047CrossRefPubMedGoogle Scholar
  23. Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729.  https://doi.org/10.1164/ajrccm.163.7.2011060CrossRefPubMedGoogle Scholar
  24. Jónsson B, Tullus K, Brauner A, Lu Y, Noack G (1997) 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 77:F198–F201CrossRefGoogle Scholar
  25. Joung KE, Kim HS, Lee J, Shim GH, Choi CW, Kim EK et al (2011) Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia. Free Radic Res 45:1024–1032.  https://doi.org/10.3109/10715762.2011.588229CrossRefPubMedGoogle Scholar
  26. Kalikkot Thekkeveedu R, Guaman MC, Shivanna B (2017) Bronchopulmonary dysplasia: a review of pathogenesis and pathophysiology. Respir Med 132:170–177.  https://doi.org/10.1016/j.rmed.2017.10.014CrossRefPubMedGoogle Scholar
  27. Kinsella JP, Greenough A, Abman SH (2006) Bronchopulmonary dysplasia. Lancet 367:1421–1431CrossRefGoogle Scholar
  28. Kuligowski J, Aguar M, Rook D, Lliso I, Torres-Cuevas I, Escobar J et al (2015) Urinary lipid peroxidation byproducts: are they relevant for predicting neonatal morbidity in preterm infants? Antioxid Redox Signal 23:178–184.  https://doi.org/10.1089/ars.2015.6262CrossRefPubMedPubMedCentralGoogle Scholar
  29. Leroy S, Caumette E, Waddington C, Hébert A, Brant R, Lavoie PM (2018) A time-based analysis of inflammation in infants at risk of bronchopulmonary dysplasia. J Pediatr 192:60–65.  https://doi.org/10.1016/j.jpeds.2017.09.011CrossRefPubMedGoogle Scholar
  30. Lu HY, Zhang J, Wang QX (2015) Activation of the endoplasmic reticulum stress pathway involving CHOP in the lungs of rats with hyperoxia -induced bronchopulmonary dysplasia. Mol Med Rep 2:4494–4500CrossRefGoogle Scholar
  31. Matthews MA, Aschner JL, Stark AR, Moore PE, Slaughter JC, Steele S et al (2016) Increasing F2-isoprostanes in the first month after birth predicts poor respiratory and neurodevelopmental outcomes in very preterm infants. J Perinatol 36:779–783.  https://doi.org/10.1038/jp.2016.74CrossRefPubMedPubMedCentralGoogle Scholar
  32. McEvoy CT, Aschner JL (2015) The natural history of Bronchopulmonary dysplasia: The Case for Primary Prevention. Clin Perinatol 42:911–931.  https://doi.org/10.1016/j.clp.2015.08.014CrossRefPubMedPubMedCentralGoogle Scholar
  33. Moore TA, Schmid KK, Anderson-Berry A, Berger AM (2016) Lung disease, oxidative stress, and oxygen requirements in preterm infants. Biol Res Nurs 18:322–330.  https://doi.org/10.1177/1099800415611746CrossRefPubMedGoogle Scholar
  34. Negi R, Pande D, Karki K, Kumar A, Khanna RS, Kanna HD (2014) A novel approach to study oxidative stress in neonatal respiratory distress syndrome. BBA Clin 3:65–69.  https://doi.org/10.1016/j.bbacli.2014.12.001CrossRefPubMedPubMedCentralGoogle Scholar
  35. Northway WH, Rosan RC, Porter DY (1967) Pulmonary disease following respirator therapy of hyaline-membrane disease. N Engl J Med 276:357–368CrossRefGoogle Scholar
  36. Nozik-Grayck E, Suliman HB, Majka S, Albietz J, Van Rheen Z, Roush K et al (2008) Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodelling. Am J Physiol Lung Cell Mol Physiol 295:L422–L430.  https://doi.org/10.1152/ajplung.90293.2008CrossRefPubMedPubMedCentralGoogle Scholar
  37. Perrone S, Negro S, Tataranno ML, Buonocore G (2010) Oxidative stress and antioxidant strategies in newborns. J Matern Fetal Neonatal Med Suppl 3:63–65.  https://doi.org/10.3109/14767058.2010.509940CrossRefGoogle Scholar
  38. Perrone S, Tataranno ML, Buonocore G (2012) Oxidative stress and bronchopulmonary dysplasia. J Clin Neonatol 1:109–114.  https://doi.org/10.4103/2249-4847.101683CrossRefPubMedPubMedCentralGoogle Scholar
  39. Perrone S, Santacroce A, Longini M, Proietti F, Bazzini F, Buonocore G (2018) The free radical diseases of prematurity: from cellular mechanism to bedside. Oxidative Med Cell Longev 2018:7483062.  https://doi.org/10.1155/2018/7483062CrossRefGoogle Scholar
  40. Poggi C, Dani C (2014) Antioxidant strategies and respiratory disease of the preterm newborn: an update. Oxidative Med Cell Longev 2014:721043.  https://doi.org/10.1155/2014/721043CrossRefGoogle Scholar
  41. Ryan RM, Ahmed Q, Lakshminrusimha S (2008) Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia. Clin Rev Allergy Immunol 34:174–190.  https://doi.org/10.1007/s12016-007-8031-4CrossRefPubMedGoogle Scholar
  42. Sampath V, Garland JS, Helbling D, Dimmock D, Mulrooney NP, Simpson PM et al (2015) Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants. Pediatr Res 77:477–483.  https://doi.org/10.1038/pr.2014.200CrossRefPubMedGoogle Scholar
  43. Sandal G, Mutlu B, Uras N, Erdeve O, Oguz SS, Dilmen U (2013) Evaluation of treatment with hydrocortisone on oxidant/antioxidant system in preterm infants with BPD. Eur Rev Med Pharmacol Sci 17:2594–2597PubMedGoogle Scholar
  44. Saugstad OD (2003) Bronchopulmonary dysplasia-oxidative stress and antioxidants. Semin Neonatol 8:39–49CrossRefGoogle Scholar
  45. Shah VS, Ohlsson A, Halliday HL (2017a) Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates. Cochrane Database Syst Rev 1:CD001969PubMedGoogle Scholar
  46. Shah SSL, Ohlsson A, Halliday HL (2017b) Inhaled versus systemic corticosteroids for the treatment of bronchopulmonary dysplasia in ventilated very low birth weight preterm infants. Cochrane Database Syst Rev 10:CD002057PubMedGoogle Scholar
  47. Suresh GK, Davis JM, Soll RF (2001) Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants. Cochrane Database Syst Rev 2001(1):CD001968.  https://doi.org/10.1002/14651858.CD001968CrossRefGoogle Scholar
  48. Vento M, Aguar M, Escobar J, Arduini A, Escig R, Brugada M et al (2009) Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. Antioxid Redox Signal 11:2945–2955.  https://doi.org/10.1089/ars.2009.2671CrossRefPubMedGoogle Scholar
  49. Wang J, Dong W (2018) Oxidative stress and bronchopulmonary dysplasia. Gene 678:177–183.  https://doi.org/10.1016/j.gene.2018.08.031CrossRefPubMedGoogle Scholar
  50. Wardle SP, Hughes A, Chen S, Shaw NJ (2001) Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease. Arch Dis Child Fetal Neonatal Ed 84:F9–F13CrossRefGoogle Scholar
  51. Wilborn AM, Evers LB, Canada AT (1996) Oxygen toxicity to the developing lung of the mouse: role of reactive oxygen species. Pediatr Res 10:225–232.  https://doi.org/10.1203/00006450-199608000-00007CrossRefGoogle Scholar
  52. Zhang L, Zhao S, Yuan L, Wu H, Jiang H, Zhao SM et al (2015) Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells. Mol Cell Biochem 408:181–189.  https://doi.org/10.1007/s11010-015-2494-zCrossRefPubMedGoogle Scholar
  53. Zhang L, Zhao S, Yuan L, Wu H, Jiang H, Luo G (2016) Hyperoxia-mediated LC3B activation contributes to the impaired transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs). Clin Exp Pharmacol Physiol 43(9):834–843.  https://doi.org/10.1111/1440-1681.12592CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Serafina Perrone
    • 1
  • Elisa Laschi
    • 1
  • Elisabetta Grande
    • 1
  • Giuseppe Buonocore
    • 1
  1. 1.Department of Molecular and Developmental MedicineUniversity of SienaSienaItaly

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