Pulmonary hypertension in bronchopulmonary dysplasia

Pediatr Res. 2021 Feb;89(3):446-455. doi: 10.1038/s41390-020-0993-4. Epub 2020 Jun 10.

Abstract

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / blood
  • Bronchopulmonary Dysplasia / complications*
  • Bronchopulmonary Dysplasia / diagnosis
  • Bronchopulmonary Dysplasia / physiopathology
  • Bronchopulmonary Dysplasia / therapy
  • Cardiac Catheterization
  • Cardiac Surgical Procedures
  • Echocardiography
  • Endothelin Receptor Antagonists / therapeutic use
  • Heart Failure / etiology
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / physiopathology
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / physiopathology*
  • Magnetic Resonance Imaging
  • Nitric Oxide / metabolism
  • Oxygen Inhalation Therapy
  • Prostaglandins I / therapeutic use
  • Sildenafil Citrate / therapeutic use
  • Tomography, X-Ray Computed
  • Tricuspid Valve Insufficiency / diagnostic imaging
  • Tricuspid Valve Insufficiency / etiology
  • Vascular Resistance
  • Vasodilator Agents / therapeutic use

Substances

  • Biomarkers
  • Endothelin Receptor Antagonists
  • Prostaglandins I
  • Vasodilator Agents
  • Nitric Oxide
  • Sildenafil Citrate