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Respiratory Outcomes in Preterm Infants pp 197–213Cite as

Pulmonary Hypertension in Bronchopulmonary Dysplasia

Part of the Respiratory Medicine book series (RM)

Abstract

Pulmonary vascular disease (PVD) and related pulmonary hypertension (PH) contribute significantly to the pathogenesis, cardiorespiratory morbidities, and poor outcomes in preterm infants with BPD. Past studies have shown that persistent echocardiogram evidence of PH beyond the first few months of life is associated with up to 40 % mortality in infants with BPD. The association of PH with poor survival in BPD has continued into the recent era of the “new BPD,” especially in infants with severe disease who require prolonged support with mechanical ventilation. More recent studies have shown that adverse antenatal or early postnatal stimuli impair pulmonary vascular development and function, leading to disruption of angiogenesis and distal lung airspace growth. Consensus guidelines for the diagnosis, evaluation, and management of PH in infants with established BPD have recently been published by a consensus committee; however, clinical care remains controversial due to the lack of strong evidence-based data. Overall, understanding the pathogenesis and pathobiology of early PVD in BPD continues as an important challenge and may help to improve early and late cardiopulmonary outcomes after preterm birth. Future large-scale studies of interventions for the treatment of PH in established BPD are needed. In addition, strategies that specifically target the preservation of endothelial survival and function may also lead to novel approaches for the prevention of BPD and late PH.

Keywords

  • Pulmonary arterial hypertension
  • Prematurity
  • Bronchopulmonary dysplasia
  • Pulmonary vascular disease
  • Lung vascular development
  • Inhaled nitric oxide

Funding Source 

This work was supported in part by grants from the NHLBI HL085703 (S.H.A.), HL068702 (S.H.A.), and U01 HL102235 (S.H.A.). The author has no conflicts of interest with this work, but has received grant funding from Shire Pharmaceuticals for laboratory research

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References

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

    CrossRef  PubMed  Google Scholar 

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

    CAS  CrossRef  PubMed  Google Scholar 

  3. Jobe AH. The new BPD: an arrest of lung development. Pediatr Res. 1999;46:641–3.

    CAS  CrossRef  PubMed  Google Scholar 

  4. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357(19):1946–55.

    CAS  CrossRef  PubMed  Google Scholar 

  5. Hussain AN, Siddiqui NH, Stocker JT. Pathology of arrested acinar development in postsurfactant BPD. Hum Pathol. 1998;29:710–7.

    CrossRef  Google Scholar 

  6. McEvoy C, Jain L, Schmidt B, Abman SH, Bancalari E, Aschner J. Bronchopulmonary dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc. 2014;Suppl 3:S146–53.

    CrossRef  Google Scholar 

  7. Stoll BJ, Hansen NI, Bell EF, et al. Trends in care practices, morbidity and mortality of extremely preterm neonates. JAMA. 2015;314:1039–51.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  8. Wong PM, Lees AN, Louw J, et al. Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia. Eur Respir J. 2008;32(2):321–8.

    CAS  CrossRef  PubMed  Google Scholar 

  9. Hislop AA, Haworth SG. Pulmonary vascular damage and the development of cor pulmonale following hyaline membrane disease. Pediatr Pulmonol. 1990;9:152–161.

    Google Scholar 

  10. Bush A, Busst CM, Knight WB, Hislop AA, Haworth SG, Shinebourne EA. Changes in the pulmonary circulation in BPD. Arch Dis Child. 1990;65:739–45.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  11. Fouron JC, Le Guennec JC, Villemant D, et al. Value of echocardiography in assessing the outcome of bronchopulmonary dysplasia of the newborn. Pediatrics. 1980;65(3):529–35.

    CAS  PubMed  Google Scholar 

  12. Abman SH. Pulmonary hypertension in chronic lung disease of infancy. Pathogenesis, pathophysiology and treatment. In: Bland RD, Coalson JJ, editors. Chronic lung disease of infancy. New York: Marcel Dekker; 2000. p. 619–68.

    Google Scholar 

  13. Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, Poindexter BB, Ingram DA, Abman SH. Early pulmonary vascular disease in preterm infants at risk for BPD. Am J Respir Crit Care Med. 2015;191:87–95.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  14. Mirza H, Ziegler J, Ford S, Padbury J, Tucker R, Laptook A. Pulmonary hypertension in preterm infants: prevalence and association with bronchopulmonary dysplasia. J Pediatr. 2014;165(5):909–14.e1.

    CrossRef  PubMed  Google Scholar 

  15. Khemani E, McElhinney DB, Rhein L, et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007;120(6):1260–9.

    CrossRef  PubMed  Google Scholar 

  16. Abman SH, Hansmann G, Archer S, et al. American Heart Association and American Thoracic Society Joint Guidelines for Pediatric Pulmonary Hypertension. Circulation. 2015;132:2037–99.

    CrossRef  PubMed  Google Scholar 

  17. Stenmark KR, Abman SH. Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol. 2005;67:623–61.

    CAS  CrossRef  PubMed  Google Scholar 

  18. 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.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  19. Bhatt AJ, Pryhuber GS, Huyck H, et al. Disrupted pulmonary vasculature and decreased VEGF, flt-1, and Tie 2 in human infants dying with BPD. Am J Respir Crit Care Med. 2000;164:1971–80.

    CrossRef  Google Scholar 

  20. Lassus P, Turanlahti M, Heikkila P, et al. Pulmonary vascular endothelial growth factor and Flt-1 in fetuses, in acute and chronic lung disease, and in persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1981–7.

    CAS  CrossRef  PubMed  Google Scholar 

  21. De Paepe ME, Mao Q, Powell J, et al. Growth of pulmonary microvasculature in ventilated preterm infants. Am J Respir Crit Care Med. 2006;173(2):204–11.

    CrossRef  PubMed  Google Scholar 

  22. Mourani PM, Abman SH. Pulmonary vascular disease in BPD: physiology, diagnosis and treatment. In: Abman SH, editor. Bronchopulmonary dysplasia. New York: Informa; 2010. p. 347–63.

    Google Scholar 

  23. Jakkula M, Le Cras TD, Gebb S, et al. Inhibition of angiogenesis decreases alveolarization in the developing rat lung. Am J Physiol Lung Cell Mol Physiol. 2000;279:L600–7.

    CAS  PubMed  Google Scholar 

  24. Abman SH. BPD: a vascular hypothesis. Am J Respir Crit Care Med. 2001;164:1755–6.

    CAS  CrossRef  PubMed  Google Scholar 

  25. Abman SH. Impaired vascular endothelial growth factor signaling in the pathogenesis of neonatal pulmonary vascular disease. Adv Exp Med Biol. 2010;661:323–35.

    CAS  CrossRef  PubMed  Google Scholar 

  26. Balinotti JE, Chakr VC, Tiller C, et al. Growth of lung parenchyma in infants and toddlers with chronic lung disease of infancy. Am J Respir Crit Care Med. 2010;181(10):1093–7.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  27. Hansen AR, Barnes CM, Folkman J, McElrath TF. Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr. 2010;156(4):532–6.

    CrossRef  PubMed  Google Scholar 

  28. Foidart JM, Schaaps JP, Chantraine F, Munaut C, Lorquet S. Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia – a step forward but not the definitive answer. J Reprod Immunol. 2009;82(2):106–11.

    CAS  CrossRef  PubMed  Google Scholar 

  29. Tang JR, Karumanchi SA, Seedorf G, Markham N, Abman SH. Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2012;302(1):L36–46.

    CAS  CrossRef  PubMed  Google Scholar 

  30. Li F, Hagaman JR, Kim HS, et al. eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype. J Am Soc Nephrol. 2012;23(4):652–60.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  31. Rozance PJ, Seedorf GJ, Brown A, et al. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2011;301(6):L860–71.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  32. Check J, Gotteiner N, Liu X, et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol. 2013;33:553–7.

    Google Scholar 

  33. Evans NJ, Archer LNJ. Doppler assessment of pulmonary artery pressure during recovery from hyaline membrane disease. Arch Dis Child. 1991;66:802–4.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  34. Subhedar NV, Shaw NJ. Changes in pulmonary arterial pressure in preterm infants with chronic lung disease. Arch Dis Child. 2000;82:F243–7.

    CAS  CrossRef  Google Scholar 

  35. Czernik C, Rhode S, Metze B, Schmalisch G, Buhrer C. Persistently elevated right ventricular index of myocardial performance in preterm infants with incipient bronchopulmonary dysplasia. PLoS One. 2012;7(6):e38352.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  36. Skinner JR, Boys RJ, Hunter S, Hey EN. Pulmonary and systemic arterial pressure in hyaline membrane disease. Arch Dis Child. 1992;67(4 Spec No):366–73.

    Google Scholar 

  37. Abman SH, Wolfe RR, Accurso FJ, Koops BL, Wiggins JW. Pulmonary vascular response to to oxygen in infants with severe BPD. Pediatrics. 1985;75:80–4.

    CAS  PubMed  Google Scholar 

  38. Mourani P, Ivy DD, Gao D, Abman SH. Pulmonary vascular effects of inhaled NO and oxygen tension in older children and adolescents with bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2004;170:1006–13.

    CrossRef  PubMed  Google Scholar 

  39. Galambos C, Sims-Lucas S, Abman SH. Histologic evidence of intrapulmonary arteriovenous shunt vessels in premature infants with severe bpd. Ann Am Thorac Soc. 2013;10:474–81.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  40. Abman SH, Schaffer MS, Wiggins JW, et al. Pulmonary vascular extraction of circulating norepinephrine in infants with BPD. Pediatr Pulmonol. 1987;3:386–91.

    CAS  CrossRef  PubMed  Google Scholar 

  41. An HS, Bae EJ, Kim GB, et al. Pulmonary hypertension in preterm infants with BPD. Korean Circ J. 2010;40:131–6.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  42. Slaughter JR, Pakradhi T, Lones DE et al. Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with BPD requiring prolonged positive pressure ventilation. J Perinatol. 2011;31:1–6.

    Google Scholar 

  43. Currie PJ, Seward JB, Chan KL, et al. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol. 1985;6(4):750–6.

    CAS  CrossRef  PubMed  Google Scholar 

  44. Mourani PM, Sontag MK, Younoszai A, et al. Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics. 2008;121(2):317.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  45. Drossner DM, Kim DW, Maher KO, et al. Pulmonary vein stenosis: prematurity and associated conditions. Pediatrics. 2008;122:e656–61.

    CrossRef  PubMed  Google Scholar 

  46. Mourani PM, Fagan T, Ivy DD, Rosenberg A, Abman SH. Left ventricular diastolic dysfunction in bronchopulmonary dysplasia. J Pediatr. 2008;152:291–3.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  47. Del Cerro MJ, Sabate-Rotes A, Carton A, et al. Pulmonary hypertension in BPD: clinical findings, cardiovascular abnormalities and outcomes. Pediatr Pulmonol. 2014;49:49–59.

    CrossRef  PubMed  Google Scholar 

  48. Banks BA, Seri I, Ischiropoulos H, et al. Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia. Pediatrics. 1999;103(3):610–8.

    CAS  CrossRef  PubMed  Google Scholar 

  49. Baquero H, Soliz A, Neira F, et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics. 2006;117(4):1077–83.

    CrossRef  PubMed  Google Scholar 

  50. Humpl T, Reyes JT, Holtby H, et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation. 2005;111(24):3274–80.

    CAS  CrossRef  PubMed  Google Scholar 

  51. Mourani PM, Sontag MK, Lui G, et al. Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr. 2008;121:317–25.

    Google Scholar 

  52. Rosenzweig EB, Ivy DD, Widlitz A, et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005;46(4):697–704.

    CAS  CrossRef  PubMed  Google Scholar 

  53. Brownlee JR, Beekman RH, Rosenthal A. Acute hemodynamic effects of nifedipine in infants with bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res. 1988;24(2):186–90.

    CAS  CrossRef  PubMed  Google Scholar 

  54. Johnson CE, Beekman RH, Kostyshak DA, et al. Pharmacokinetics and pharmacodynamics of nifedipine in children with bronchopulmonary dysplasia and pulmonary hypertension. Pediatr Res. 1991;29(5):500–3.

    CAS  CrossRef  PubMed  Google Scholar 

  55. Ferdman DJ, Rosenzweig EB, Zuckerman WA, Krishnan U. Subcutaneous treprostinil for pulmonary hypertension in chronic lung disease of infancy. Pediatrics. 2014;134:e274–8.

    CrossRef  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pediatric Heart Lung Center, Sections of Pediatric Pulmonary Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, 80045, USA

    Steven H. Abman MD

  2. Critical Care Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, 80045, USA

    Steven H. Abman MD

  3. Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Mail Stop B395, 13123 East 16th Avenue, Aurora, CO, 80045, USA

    Steven H. Abman MD

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  1. Steven H. Abman MD
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Correspondence to Steven H. Abman MD .

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Editors and Affiliations

  1. Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA

    Anna Maria Hibbs

  2. Department of Pediatrics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA

    Marianne S. Muhlebach

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Abman, S.H. (2017). Pulmonary Hypertension in Bronchopulmonary Dysplasia. In: Hibbs, A., Muhlebach , M. (eds) Respiratory Outcomes in Preterm Infants. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-48835-6_12

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  • DOI: https://doi.org/10.1007/978-3-319-48835-6_12

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