Jumat , 14 Jan 2022 12:44:55
Characterisation of paediatric pulmonary hypertensive vascular disease from the PPHNet Registry


Steven H. Abman, Mary P. Mullen, Lynn A. Sleeper, Eric D. Austin, Erika B. Rosenzweig, John P. Kinsella, Dunbar Ivy, Rachel K. Hopper, J. Usha Raj, Jeffrey Fineman, Roberta L. Keller, Angela Bates, Usha S. Krishnan, Catherine M. Avitabile, Alexander Davidson, Marc D. Natter, Kenneth D. Mandl for the Pediatric Pulmonary Hypertension Network

European Respiratory Journal 2022 59: 2003337; DOI: 10.1183/13993003.03337-2020

Extract

Background There are limited data about the range of diseases, natural history, age-appropriate end-points and optimal care for children with pulmonary hypertension (PH), including the need for developing high-quality patient registries of children with diverse forms of PH to enhance care and research. Our objective was to characterise the distribution and clinical features of diseases associated with paediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the World Symposium on Pulmonary Hypertension (WSPH) classification.

Methods 1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of eight interdisciplinary PH programmes.

Results WSPH Groups 1 (pulmonary arterial hypertension (PAH)) and 3 (lung or hypoxia-related PH) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were bronchopulmonary dysplasia and congenital diaphragmatic hernia. Group 1 disease was predominantly associated with congenital heart disease (60% of Group 1 cases) and idiopathic PAH (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (hazard ratio 3.1; p<0.001), tended to be younger at diagnosis (median (interquartile range) age 0.3 (0.0–0.6) versus 1.6 (0.1–6.9) years; p<0.001) and were more often male (57% versus 45%; p<0.001). Down syndrome, the most common genetic syndrome in the PPHNet Registry, constituted 11% of the entire PH cohort.

Conclusions We find a striking proportion of paediatric PH patients with Group 3 disorders, reflecting the growing recognition of PH in diverse developmental lung diseases. Greater precision of clinical phenotyping based on disease-specific characterisation may further enhance care and research of paediatric PH.

To characterise the clinical features of diseases associated with paediatric pulmonary hypertension, including natural history, evaluation and therapeutic interventions, longitudinal data from 1500 children from major PH programmes were analysed https://bit.ly/3ff3zjV

Acknowledgements

We are grateful for contributions of other members of the Pediatric Pulmonary Hypertension Network (PPHNet), including: Allan Everett and Lew Romer (Johns Hopkins University Medical School), Delphine Yung (University of Washington School of Medicine), Stephanie Handler (University of Wisconsin Milwaukee), Nidhy Varghese (Texas Children's Hospital), Russel Hirsch (Cincinnati Children's Hospital and Medical Center), Robin Steinhorn (University of California San Diego), Rolf Berger (University Medical College, Groningen, The Netherlands), Wendy Chung (Columbia University School of Medicine), David Cornfield (Stanford University School of Medicine), Csaba Galambos (University of Colorado) and Minmin Lu (Boston Children's Hospital).

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Conflict of interest: S.H. Abman has nothing to disclose.

  • Conflict of interest: M.P. Mullen reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study; personal fees from Actelion, outside the submitted work.

  • Conflict of interest: L.A. Sleeper reports grants from the National Heart, Lung, and Blood Institute (subcontract from University of Colorado), during the conduct of the study.

  • Conflict of interest: E.D. Austin has nothing to disclose.

  • Conflict of interest: E.B. Rosenzweig reports grants from the National Institutes of Health, during the conduct of the study.

  • Conflict of interest: J.P. Kinsella has nothing to disclose.

  • Conflict of interest: The University of Colorado contracts with Actelion, Bayer, Gilead and United Therapeutics for D. Ivy to be a consultant and preform clinical research trials.

  • Conflict of interest: R.K. Hopper has nothing to disclose.

  • Conflict of interest: J.U. Raj has nothing to disclose.

  • Conflict of interest: J. Fineman has nothing to disclose.

  • Conflict of interest: R.L. Keller reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study.

  • Conflict of interest: A. Bates has nothing to disclose.

  • Conflict of interest: U.S. Krishnan has nothing to disclose.

  • Conflict of interest: C.M. Avitabile has nothing to disclose.

  • Conflict of interest: A. Davidson has nothing to disclose.

  • Conflict of interest: M.D. Natter reports grants from the National Heart, Lung, and Blood Institute, during the conduct of the study.

  • Conflict of interest: K.D. Mandl reports no specific conflicts, however in the interest of full disclosure, reports personal fees from Merck, and philanthropy from Eli Lily to his lab, during the conduct of the study.

  • Support statement: This work was supported by grant U01 HL12118 (Data Fusion: A Sustainable, Open Source Registry Advancing Pediatric Pulmonary Vascular Disease Research; K.D. Mandl and S.H. Abman) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or NIH. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received September 12, 2020.
  • Accepted May 15, 2021.
  • Copyright ©The authors 2022. For reproduction rights and permissions contact