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Bronchopulmonary dysplasia

Nature Reviews Disease Primers volume 5, Article number: 78 (2019) Cite this article

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Abstract

In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants.

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Fig. 1: Timeline and stages of BPD.
Fig. 2: Patterns of lung disease in premature infants.
Fig. 3: Structure of the alveolar gas exchange region.
Fig. 4: Human lung morphogenesis.
Fig. 5: Structural changes in the lung during development and in BPD.
Fig. 6: Pulmonary vascular disease in BPD.
Fig. 7: Alternative ventilation strategies in the treatment of heterogeneous lung disease in severe BPD.
Fig. 8: Structural changes in the lungs in severe BPD.
Fig. 9: Persistent subclinical pulmonary vascular disease in BPD.

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Acknowledgements

This work was supported by National Heart, Lung and Blood Institute of the US National Institutes of Health (NIH) grants (U01HL122642 and U01HL134745 to J.A.W.; RO1HL68702, R01HL145679 and U01HL12118-01 to S.H.A.; and K24 HL143283 to M.L.), and funding from the Australian National Health and Medical Research Council (NHMRC) to P.G.D. and from the Canadian Institute for Health Research, Stem Cell Network and the Ontario Institute for Regenerative Medicine to B.T. The authors thank J. Kitzmiller and C.-L. Na for their contributions in obtaining images.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Children’s Hospital of Eastern Ontario (CHEO) and CHEO Research Institute, Ottawa, Ontario, Canada

    Bernard Thébaud

  2. Ottawa Hospital Research Institute, Sinclair Centre for Regenerative Medicine, Ottawa, Ontario, Canada

    Bernard Thébaud

  3. Departments of Medicine and Pediatrics, University of Wisconsin-Madison, Madison, WI, USA

    Kara N. Goss

  4. The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Matthew Laughon

  5. Cincinnati Children’s Hospital Medical Center, Division of Neonatology, Pulmonary Biology, University of Cincinnati, Cincinnati, OH, USA

    Jeffrey A. Whitsett & Alan H. Jobe

  6. Pediatric Heart Lung Center, Section of Pulmonary Medicine, Department of Pediatrics, Children’s Hospital Colorado and the University of Colorado Denver Anschutz Medical Center, Aurora, CO, USA

    Steven H. Abman

  7. Children’s National Medical Center, Department of Pediatrics, Washington, DC, USA

    Robin H. Steinhorn

  8. Joseph M. Sanzari Children’s Hospital, Hackensack Meridian Health School of Medicine, Hackensack, NJ, USA

    Judy L. Aschner

  9. Albert Einstein College of Medicine, Bronx, NY, USA

    Judy L. Aschner

  10. The Royal Women’s Hospital, University of Melbourne, Melbourne, Victoria, Australia

    Peter G. Davis

  11. Department of Pediatrics, Eudowood Division of Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sharon A. McGrath-Morrow

  12. Department of Pediatrics, Larner School of Medicine, University of Vermont, Burlington, VT, USA

    Roger F. Soll

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Contributions

Introduction (B.T.); Epidemiology (M.L. and B.T.); Mechanisms/pathophysiology (J.A.W., S.H.A., A.H.J. and B.T.); Diagnosis, screening and prevention (R.H.S., J.L.A. and B.T.); Management (P.G.D., S.H.A. and B.T.); Quality of life (K.N.G., S.A.McG.-M. and B.T.); Outlook (R.F.S. and B.T.); Overview of the Primer (B.T.).

Corresponding author

Correspondence to Bernard Thébaud.

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Competing interests

A.H.J. consults occasionally for Chiesi Farmaceutici about BPD and surfactant. S.H.A has served as a consultant for Takeda Pharmaceuticals. R.H.S. is a consultant for Takeda Pharmaceutical Company and for Actelion Pharmaceutical Ltd. The remaining authors declare no competing interests.

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Nature Reviews Disease Primers thanks Y.S. Chang, M. Hallman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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NICHD NRN risk estimator: https://neonatal.rti.org/index.cfm

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Thébaud, B., Goss, K.N., Laughon, M. et al. Bronchopulmonary dysplasia. Nat Rev Dis Primers 5, 78 (2019). https://doi.org/10.1038/s41572-019-0127-7

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