Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure

Mary K. Dahmer; Heidi Flori; Anil Sapru; Joseph Kohne; Heidi M. Weeks; Martha A.Q. Curley; Michael A. Matthay; Michael W. Quasney; Scot T. Bateman; M. D. Berg; Santiago Borasino; G. Kris Bysani; Allison S. Cowl; Cindy Darnell Bowens; E. Vincent S. Faustino; Lori D. Fineman; A. J. Godshall; Ellie Hirshberg; Aileen L. Kirby; Gwenn E. McLaughlin; Shivanand Medar; Phineas P. Oren; James B. Schneider; Adam J. Schwarz; Thomas P. Shanley; Lauren R. Sorce; Edward J. Truemper; Michele A. Vander Heyden; Kim Wittmayer; Athena Zuppa; David Wypij

doi:10.1016/j.chest.2020.03.041

Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure

Mary K. Dahmer, Heidi Flori, Anil Sapru, Joseph Kohne, Heidi M. Weeks, Martha A.Q. Curley, Michael A. Matthay, Michael W. Quasney^*, Scot T. Bateman, M. D. Berg, Santiago Borasino, G. Kris Bysani, Allison S. Cowl, Cindy Darnell Bowens, E. Vincent S. Faustino, Lori D. Fineman, A. J. Godshall, Ellie Hirshberg, Aileen L. Kirby, Gwenn E. McLaughlinShivanand Medar, Phineas P. Oren, James B. Schneider, Adam J. Schwarz, Thomas P. Shanley, Lauren R. Sorce, Edward J. Truemper, Michele A. Vander Heyden, Kim Wittmayer, Athena Zuppa, David Wypij

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? Study Design and Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay. Results: Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (r_s = 0.16, P = .002). Interpretation: Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.

Original language	English (US)
Pages (from-to)	1027-1035
Number of pages	9
Journal	CHEST
Volume	158
Issue number	3
DOIs	https://doi.org/10.1016/j.chest.2020.03.041
State	Published - Sep 2020

Funding

FUNDING/SUPPORT: This study was funded by a grant from the NIH awarded to Drs. Dahmer, Flori and Quasney (R01HL095410). The parent study was supported by grants from the NIH awarded to Drs. Curley and Wypij (U01HL086622, U01 HL086649). Author contributions: M. K. D. had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. M. K. D. H. F. A. S. M. W. Q. and M. A. M. contributed to study concept and design. M. K. D. H. F. A. S. J. K. and M. A. Q. contributed to data collection. H. M. W. and J. K. did the statistical analysis with input from M. K. D. and H. F. All authors were involved with interpretation of data. M. K. D. H. F. J. K. H. M. W. and M. W. Q. were involved with drafting of the manuscript. All authors critically edited the manuscript for important intellectual content. All authors approved the final version before submission. Financial/nonfinancial disclosures: None declared. ?BALI and RESTORE Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Collaborators: We acknowledge the contribution of the subgroup of PALISI members who were BALI study investigators at the sites that participated in the RESTORE study, including: Scot T. Bateman (University of Massachusetts Memorial Children's Medical Center, Worcester, MA), M. D. Berg (University of Arizona Medical Center, Tucson, AZ), Santiago Borasino (Children's Hospital of Alabama, Birmingham, AL), G. Kris Bysani (Medical City Children's Hospital, Dallas, TX), Allison S. Cowl (Connecticut Children's Medical Center, Hartford, CT), Cindy Darnell Bowens (Children's Medical Center of Dallas, Dallas, TX), E. Vincent S. Faustino (Yale-New Haven Children's Hospital, New Haven, CT), Lori D. Fineman (University of California San Francisco Benioff Children's Hospital at San Francisco, San Francisco, CA), A. J. Godshall (Florida Hospital for Children, Orlando, FL), Ellie Hirshberg (Primary Children's Medical Center, Salt Lake City, UT), Aileen L. Kirby (Oregon Health & Science University Doernbecher Children's Hospital, Portland, OR), Gwenn E. McLaughlin (Holtz Children's Hospital, Jackson Health System, Miami, FL), Shivanand Medar (Cohen Children's Medical Center of New York, Hyde Park, NY), Phineas P. Oren (St. Louis Children's Hospital, St. Louis, MO), James B. Schneider (Cohen Children's Medical Center of New York, Hyde Park, NY), Adam J. Schwarz (Children's Hospital of Orange County, Orange, CA), Thomas P. Shanley (C. S. Mott Children's Hospital at the University of Michigan, Ann Arbor, MI), Lauren R. Sorce (Ann & Robert H. Lurie, Children's Hospital of Chicago, Chicago, IL), Edward J. Truemper (Children's Hospital and Medical Center, Omaha, NE), Michele A. Vander Heyden (Children's Hospital at Dartmouth, Dartmouth, NH), Kim Wittmayer (Advocate Hope Children's Hospital, IL), Athena Zuppa (Children's Hospital of Philadelphia, Philadelphia, PA) and the RESTORE data coordination center led by David Wypij, PhD (Department of Biostatistics, Harvard School of Public Health, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, Boston, MA). Role of sponsors: The sponsor had no role in the design, data collection, analyses, interpretation of data, writing of the manuscript, or the decision to submit the study for publication. Other contributions: We thank the study participants and their families and guardians for their participation in this study. Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: This study was funded by a grant from the NIH awarded to Drs. Dahmer, Flori and Quasney (R01HL095410). The parent study was supported by grants from the NIH awarded to Drs. Curley and Wypij (U01HL086622, U01 HL086649).

Keywords

ARDS
biomarker
critical illness
length of mechanical ventilation
mortality
outcome
pediatric ARDS
pediatrics
surfactant

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine
Cardiology and Cardiovascular Medicine

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10.1016/j.chest.2020.03.041

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Dahmer, M. K., Flori, H., Sapru, A., Kohne, J., Weeks, H. M., Curley, M. A. Q., Matthay, M. A., Quasney, M. W., Bateman, S. T., Berg, M. D., Borasino, S., Bysani, G. K., Cowl, A. S., Bowens, C. D., Faustino, E. V. S., Fineman, L. D., Godshall, A. J., Hirshberg, E., Kirby, A. L., ... Wypij, D. (2020). Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure. CHEST, 158(3), 1027-1035. https://doi.org/10.1016/j.chest.2020.03.041

@article{78f5ad5a78cf49ae9d680cda82677d5a,

title = "Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure",

abstract = "Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? Study Design and Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay. Results: Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rs = 0.16, P = .002). Interpretation: Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.",

keywords = "ARDS, biomarker, critical illness, length of mechanical ventilation, mortality, outcome, pediatric ARDS, pediatrics, surfactant",

author = "Dahmer, {Mary K.} and Heidi Flori and Anil Sapru and Joseph Kohne and Weeks, {Heidi M.} and Curley, {Martha A.Q.} and Matthay, {Michael A.} and Quasney, {Michael W.} and Bateman, {Scot T.} and Berg, {M. D.} and Santiago Borasino and Bysani, {G. Kris} and Cowl, {Allison S.} and Bowens, {Cindy Darnell} and Faustino, {E. Vincent S.} and Fineman, {Lori D.} and Godshall, {A. J.} and Ellie Hirshberg and Kirby, {Aileen L.} and McLaughlin, {Gwenn E.} and Shivanand Medar and Oren, {Phineas P.} and Schneider, {James B.} and Schwarz, {Adam J.} and Shanley, {Thomas P.} and Sorce, {Lauren R.} and Truemper, {Edward J.} and {Vander Heyden}, {Michele A.} and Kim Wittmayer and Athena Zuppa and David Wypij",

note = "Publisher Copyright: {\textcopyright} 2020 American College of Chest Physicians",

year = "2020",

month = sep,

doi = "10.1016/j.chest.2020.03.041",

language = "English (US)",

volume = "158",

pages = "1027--1035",

journal = "CHEST",

issn = "0012-3692",

publisher = "Elsevier Inc.",

number = "3",

}

Dahmer, MK, Flori, H, Sapru, A, Kohne, J, Weeks, HM, Curley, MAQ, Matthay, MA, Quasney, MW, Bateman, ST, Berg, MD, Borasino, S, Bysani, GK, Cowl, AS, Bowens, CD, Faustino, EVS, Fineman, LD, Godshall, AJ, Hirshberg, E, Kirby, AL, McLaughlin, GE, Medar, S, Oren, PP, Schneider, JB, Schwarz, AJ, Shanley, TP , Sorce, LR, Truemper, EJ, Vander Heyden, MA, Wittmayer, K, Zuppa, A & Wypij, D 2020, 'Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure', CHEST, vol. 158, no. 3, pp. 1027-1035. https://doi.org/10.1016/j.chest.2020.03.041

TY - JOUR

T1 - Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure

AU - Dahmer, Mary K.

AU - Flori, Heidi

AU - Sapru, Anil

AU - Kohne, Joseph

AU - Weeks, Heidi M.

AU - Curley, Martha A.Q.

AU - Matthay, Michael A.

AU - Quasney, Michael W.

AU - Bateman, Scot T.

AU - Berg, M. D.

AU - Borasino, Santiago

AU - Bysani, G. Kris

AU - Cowl, Allison S.

AU - Bowens, Cindy Darnell

AU - Faustino, E. Vincent S.

AU - Fineman, Lori D.

AU - Godshall, A. J.

AU - Hirshberg, Ellie

AU - Kirby, Aileen L.

AU - McLaughlin, Gwenn E.

AU - Medar, Shivanand

AU - Oren, Phineas P.

AU - Schneider, James B.

AU - Schwarz, Adam J.

AU - Shanley, Thomas P.

AU - Sorce, Lauren R.

AU - Truemper, Edward J.

AU - Vander Heyden, Michele A.

AU - Wittmayer, Kim

AU - Zuppa, Athena

AU - Wypij, David

PY - 2020/9

Y1 - 2020/9

N2 - Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? Study Design and Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay. Results: Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rs = 0.16, P = .002). Interpretation: Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.

AB - Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? Study Design and Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay. Results: Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rs = 0.16, P = .002). Interpretation: Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.

KW - ARDS

KW - biomarker

KW - critical illness

KW - length of mechanical ventilation

KW - mortality

KW - outcome

KW - pediatric ARDS

KW - pediatrics

KW - surfactant

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ER -

Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure

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