Abstract
Bronchopulmonary dysplasia (BPD) is the most common respiratory consequence of premature birth and contributes to significant short- and long-term morbidity, mortality and resource utilization. Initially defined as a radiographic, clinical and histopathological entity, the chronic lung disease known as BPD has evolved as obstetrical and neonatal care have improved the survival of lower gestational age infants. Now, definitions based on the need for supplementary oxygen at 28 days and/or 36 weeks provide a useful reference point in the neonatal intensive-care unit (NICU), but are no longer based on histopathological findings, and are neither designed to predict longer term respiratory consequences nor to study the evolution of a multifactorial disease. The aims of this review are to critically examine the evolution of the diagnosis of BPD and the challenges inherent to current classifications. We found that the increasing use of respiratory support strategies that administer ambient air without supplementary oxygen confounds oxygen-based definitions of BPD. Furthermore, lack of reproducible, genetic, biochemical and physiological biomarkers limits the ability to identify an impending BPD for early intervention, quantify disease severity for standardized classification and approaches and reliably predict the long-term outcomes. More comprehensive, multidisciplinary approaches to overcome these challenges involve longitudinal observation of extremely preterm infants, not only those with BPD, using genetic, environmental, physiological and clinical data as well as large databases of patient samples. The Prematurity and Respiratory Outcomes Program (PROP) will provide such a framework to address these challenges through high-resolution characterization of both NICU and post-NICU discharge outcomes.
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Acknowledgements
Supported by U01 HL101794 to B Schmidt, U01 HL101456 to JL Aschner, U01 HL101798 to PL Ballard and RL Keller, U01 HL101813 to GS Pryhuber, R Ryan and T Mariani, U01 HL101465 to A Hamvas and T Ferkol, U01 HL101800 to AH Jobe and CA Chougnet and 5R01HL105702 to CM Cotton, SD Davis and JA Voynow. In addition to the Principal Investigators, We acknowledge the following PROP Investigators for input into the manuscript: James Kemp, MD and Clement Ren, MD. We also acknowledge Carol J. Blaisdell, MD of NHLBI for her guidance and review of the manuscript and Lynn Taussig for his contributions as Chair of the PROP Steering Committee.
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Appendix 1
Appendix 1
Investigators and Research Staff
Cincinnati Children's Hospital Medical Center
Investigators
Claire Chougnet, PhD
Robert Frenk, MD
James M. Greenberg, MD
William Hardie, MD
Alan H. Jobe, MD, PhD
Karen McDowell, MD
Research Staff
Barbara Alexander, RN
Tari Gratton, PA
Cathy Grigsby, BSN, CCRC
Beth Koch, BHS, RRT, RPFT
Kelly Thornton, BS
Washington University School of Medicine site
Investigators
Thomas Ferkol, MD
Aaron Hamvas, MD2
Mark R. Holland, PhD
James Kemp, MD
Philip T. Levy, MD
Phillip Tarr, MD
Gautam K. Singh, MD
Barbara Warner, MD
Research Staff
Pamela Bates, CRT, RPFT, RPSGT
Claudia Cleveland, RRT
Julie Hoffmann, RN
Laura Linneman, RN
Jayne Sicard-Su, RN
Gina Simpson, RRT, CPFT
2Northwestern University Feinberg School of Medicine
University of California San Francisco site
Investigators
Philip L. Ballard, MD, PhD
Roberta A. Ballard, MD
David J. Durand, MD2
Eric C. Eichenwald, MD4
Roberta L. Keller, MD
Amir M. Khan, MD4
Leslie Lusk, MD
Jeffrey D. Merrill, MD3
Dennis W. Nielson, MD, PhD
Elizabeth E. Rogers, MD
Research Staff
Jeanette M. Asselin, MS RRT-NPS2
Samantha Balan
Katrina Burson, RN, BSN4
Cheryl Chapin
Erna Josiah-Davis, RN, NP3
Carmen Garcia, RN, CCRP4
Hart Horneman
Rick Hinojosa, BSRT, RRT, CPFT-NPS4
Christopher Johnson, MBA, RRT4
Susan Kelley, RRT
Karin L. Knowles
M. Layne Lillie, RN, BSN4
Karen Martin, RN4
Sarah Martin, RN, BSN;
Julie Arldt-McAlister, RN, BSN4
Georgia E. McDavid, RN4
Lori Pacello, RCP2
Shawna Rodgers, RN, BSN4
Daniel K. Sperry, RN4
2Children's Hospital and Research Center Oakland, Oakland, CA
3Alta Bates Summit Medical Center, Berkeley, CA
4University of Texas Health Science Center- Houston, Houston, TX
Vanderbilt University Medical Center site
Investigators
Judy Aschner, MD2
Candice Fike, MD
Scott Guthrie, MD3
Tina Hartert, MD
Nathalie Maitre, MD
Paul Moore, MD
Marshall Summar, MD4
Research Staff
Amy B Beller, BSN
Mark O’ Hunt
Theresa J. Rogers, RN
Odessa L. Settles, RN, MSN, CM
Steven Steele, RN
Sharon Wadley, BSN, RN, CLS3
2Albert Einstein College of Medicine, Bronx, NY
3Jackson-Madison County General Hospital, Jackson, TN
4Children’s National Health System, Washington, DC
University of Rochester Medical Center/University of Buffalo NY site
Investigators
Carl D’Angio, MD
Vasanth Kumar, MD
Tom Mariani, PhD
Gloria Pryhuber, MD
Clement Ren, MD
Anne Marie Reynolds, MD, MPH
Rita M. Ryan, MD1
Kristin Scheible, MD
Timothy Stevens, MD, MPH
Research Staff
Shannon Castiglione, RN
Aimee Horan, LPN
Deanna Maffet, RN
Jane O’Donnell, PNP
Michael Sacilowski, MAT
Tanya Scalise, RN, BSN
Elizabeth Werner, MPH
Jason Zayac, BS
Heidie Huyck, BS
Valerie Lunger, MS
Kim Bordeaux, RRT
Pam Brown, RRT
Julia Epping, AAS, RT
Lisa Flattery-Walsh, RRT
Donna Germuga, RRT, CPFT
Nancy Jenks, RN
Mary Platt, RN
Eileen Popplewell, RRT
Sandra Prentice, CRT
1Medical University of South Carolina, Charleston, SC
Duke Investigators
C. Michael Cotten, MD
Kim Fisher, PhD
Jack Sharp, MD
Judith A. Voynow, MD2Research Staff
Kim Ciccio, RN
2Virginia Commonwealth University
Indiana Investigators
Stephanie Davis, MD
Brenda Poindexter, MD, MS2Research Staff
Charles Clem, RRT
Susan Gunn, NNP, CCRC
Lauren Jewett, RN, CCRC
2Cincinnati Children's Hospital Medical Center
University of Pennsylvania, Perelman School of Medicine, DCC site
Investigators
Jonas Ellenberg, PhD
Rui Feng, PhD
Melissa Fernando, MPH
Howard Panitch, MD
Barbara Schmidt, MD, MSc
Pamela Shaw, PhD
Research Staff
Ann Tierney, BA, MS
Maria Blanco, BS
Denise Cifelli, MS
Sara DeMauro, MD
University of Denver, Steering Committee Chair
Lynn M. Taussig, MD
NHLBI Program Officer
Carol J. Blaisdell, MD
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Maitre, N., Ballard, R., Ellenberg, J. et al. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol 35, 313–321 (2015). https://doi.org/10.1038/jp.2015.19
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DOI: https://doi.org/10.1038/jp.2015.19
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