Abstract
Background
Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain.
Methods
Tracheal aspirates were collected from 209 treated and control infants enrolled at 7–14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant.
Results
At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p < 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p < 0.00001) and inversely related to total protein (r = 0.39, p < 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant.
Conclusions
We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant.
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Acknowledgements
We thank the TOLSURF and PROP Investigators, study coordinators, physicians, nurses, respiratory therapists, and the families who participated in the studies. This study was supported by grants from the National Health, Lung, and Blood Institute (NHLBI, U01 HL094338, U01 HL094355, U01 HL101798). Ikaria Inc. and ONY Inc. provided drug for the conduct of the parent TOLSURF trial, but neither company had input into study design, data collection, analysis and interpretation, or manuscript preparation.
Author contributions
Study design: P.B., R.K., W.T., R.B.; sample and data acquisition: all authors; data interpretation: P.B., R.K., W.T., R.B.; draft manuscript: P.B.; statistics: M.S.; review and approve manuscript: all authors; accountability for work: all authors.
Members of the TOLSURF Study Group
In addition to the authors, the following members of the TOLSURF Study Group participated in the parent trial: University of California San Francisco—Elizabeth E. Rogers, M.D., Dennis M. Black, Ph.D., Lisa Palermo, M.S., S. Hamilton Strong, J. Immamura-Ching, M. Orfanos-Villalobos, C. Williams; Alta Bates Summit Medical Center, Berkeley CA and Children’s Hospital and Research Center Oakland, Oakland CA - Jeffrey D. Merrill, M.D., David J. Durand, M.D, Jeanette M. Asselin R.T., D. Horton, L. Pacello, A. Willard; 4University of Texas Health Science Center – Houston, Houston, TX—Eric C. Eichenwald, C. Garcia M.D., G. McDavid, K. Burson, R. Hinojosa; C. Johnson, K. Miller, S. Rogers, S. Wright; Children’s Mercy Hospital, Kansas City MO—C. Gauldin, A. Holmes, P. Johnson, K. Meinert; Women and Children’s Hospital of Buffalo, Buffalo, NY—A.M. Reynolds, M.D., J. Lucie, P. Conway, M.l. Sacilowski, M. Leadersdorff, P. Orbank, K. Wynn; Anne and Robert H. Lurie Children’s Hospital/Northwestern University, Chicago IL—Robin H. Steinhorn, M.D., Nicolas F. Porta, M.D., M. deUngria, M.D., J. Khan, M.D., K. Hamann, M. Schau, B. Hopkins, J. Jenson; Stonybrook University Hospital, Stonybrook, NY—J. Shariff, R. McGovern, J. Adelman, A. Combs, M. Tjersland; University of Washington, Seattle, WA—Dennis E. Mayock, M.D., S. Walker, E. Howland, J. Longoria, H. Meo; University of Florida College of Medicine – Jacksonville, UF Jacksonville and Wolfson Children’s Hospital, Jacksonville, FL—Mark L. Hudak, M.D., K. Barnette, A. Kellum, M. Burke, C. Hayes, S. Chadwick, D. Howard, C. Kennedy, R. Prince; Wake Forest School of Medicine and Forsyth Medical Center, Winston-Salem, NC—B. Stefanescu, M.D., J. Helderman, M.D., K. Warden, P. Brown, J. Griffin, L. Conley; University of Minnesota Children’s Hospital, Minneapolis, MN—Catherine M. Bendel, M.D., M. Georgieff, M.D., B. Davern, M. Mills, S. Ritter; Medical University of South Carolina, Charleston, SC—Rita M. Ryan, M.D., Frances R. Koch, M.D., C. Wagner, M.D., D. Fanning, J. Roberson; Children’s Hospitals and Clinics of Minnesota, St. Paul, MN—Mark C. Mammel, M.D., A. Lampland, M.D., P. Meyers, A. Brey; Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN—Ellen M. Bendel-Stenzel, M.D., C. Worwa, P. Dixon, G. Ebert, C. Hejl, M. Maxwell, K. McCullough; University of Tennessee Health Science Center, Memphis TN—Ramasubbareddy Dhanireddy, M.D., MT. El Abiad, M.D., A. Talati, M.D., S. Dempsey, K. Gammage, G. Gower, K. James, P. LeNoue; all Children’s Hospital, St. Petersburg, FL—Dennis E. Mayock, M.D., S. Bell, D. Bruton, M. Beaulieu, R. Williams; Florida Hospital for Children, Orlando FL—Rajan Wadhawan, M.D., T. Michael O’Shea, M.D., R. Barron-Nelson, S. Taylor; Arkansas Children’s Hospital and University of Arkansas Medical Sciences, Little Rock, AK—Sherry E. Courtney, M.D., N. C. Sikes, G. Lowe, B. Proffitt; Clinical Coordinating Center: University of California San Francisco Department of Pediatrics—C. Chapin, H. Horneman, K. Hamann, S. Kelley; Data Coordinating Center: University of California San Francisco, Department of Epidemiology and Biostatistics—E. Vittinghoff Ph.D., J. Hietpas, L. Denton, L. Wu; Data Safety Monitoring Board: Cincinnatti Children’s Hospital Medical Center, Cincinnati, OH—A. Jobe, M.D. (Chair 2009–2010); UH Rainbow Babies and Children’s Hospital, Cleveland, OH—A. Fanaroff, M.D. (Chair 2010–2014); EMMES Corporation, Rockville, MD—T. Clemons; Boston University School of Public Health, Boston, MA—L. Glantz; Wake Forest School of Medicine, Winston-Salem, NC—D. Reboussin; Stanford University, Stanford CA—K. Van Meurs MD (2009–2010); Johns Hopkins University, Baltimore MD—M. Allen, M.D. (2010–2014) Women and Infants Hospital, Providence, RI—B. Vohr MD; Clinical Steering Committee: R. Ballard, M.D., P. Ballard, M.D., Ph.D., C. Blaisdell, M.D., D. Durand, M.D., D. Black, Ph.D., E. Eichenwald, M.D., R. Keller, M.D., M. Mammel, M.D., J. Merrill, M.D., E. Rogers, M.D., R. Ryan, M.D., W. Truog, M.D., J. Asselin, N. Newton.
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Ballard, P.L., Keller, R.L., Truog, W.E. et al. Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment. Pediatr Res 85, 305–311 (2019). https://doi.org/10.1038/s41390-018-0144-3
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DOI: https://doi.org/10.1038/s41390-018-0144-3
