Surfactant protein D is a biomarker of influenza-related pediatric lung injury
Arindam Chakrabarti PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Arindam Chakrabarti and Allen Nguyen contributed equally as co-first author.
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorAllen Nguyen MS
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorMargaret M. Newhams MPH
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMaikke B. Ohlson PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorXiaoying Yang PhD
Biostatistics, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (equal), Formal analysis (equal), Writing - review & editing (supporting)
Search for more papers by this authorSheila Ulufatu BS
Department of Safety Assessment, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorShannon Liu BA
Department of Safety Assessment, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSummer Park MS
Translational Immunology, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMin Xu PhD
Translational Immunology, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Resources (supporting), Supervision (equal), Writing - review & editing (supporting)
Search for more papers by this authorJenny Jiang MA
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorWendy G. Halpern DVM, PhD
Department of Pathology, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorVeronica G. Anania PhD
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (equal), Funding acquisition (equal), Investigation (equal), Project administration (equal), Writing - original draft (equal)
Search for more papers by this authorJacqueline M. McBride PhD
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Conceptualization (equal), Funding acquisition (lead), Project administration (lead), Resources (equal), Supervision (equal), Writing - original draft (equal)
Search for more papers by this authorCorresponding Author
Carrie M. Rosenberger PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Carrie Rosenberger and Adrienne Randolph contributed equally as senior authors.
Correspondence Adrienne Randolph, Division of Critical Care Medicine, Boston Children's Hospital, 300 Longwood Ave, Bader 634, Boston, MA 02115, USA.
Email: [email protected]
Carrie Rosenberger, PhD, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Funding acquisition (equal), Methodology (equal), Project administration (equal), Resources (lead), Supervision (lead), Writing - original draft (lead)
Search for more papers by this authorCorresponding Author
Adrienne G. Randolph MD
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Correspondence Adrienne Randolph, Division of Critical Care Medicine, Boston Children's Hospital, 300 Longwood Ave, Bader 634, Boston, MA 02115, USA.
Email: [email protected]
Carrie Rosenberger, PhD, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (equal), Funding acquisition (lead), Investigation (lead), Methodology (lead), Project administration (lead), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorThe Pediatric Intensive Care Influenza (PICFLU) Investigators
Group coauthors listed in the acknowledgments.
Search for more papers by this authorArindam Chakrabarti PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Arindam Chakrabarti and Allen Nguyen contributed equally as co-first author.
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal)
Search for more papers by this authorAllen Nguyen MS
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorMargaret M. Newhams MPH
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMaikke B. Ohlson PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Visualization (supporting), Writing - review & editing (supporting)
Search for more papers by this authorXiaoying Yang PhD
Biostatistics, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (equal), Formal analysis (equal), Writing - review & editing (supporting)
Search for more papers by this authorSheila Ulufatu BS
Department of Safety Assessment, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorShannon Liu BA
Department of Safety Assessment, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorSummer Park MS
Translational Immunology, Genentech, Inc., South San Francisco, California, USA
Contribution: Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorMin Xu PhD
Translational Immunology, Genentech, Inc., South San Francisco, California, USA
Contribution: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Resources (supporting), Supervision (equal), Writing - review & editing (supporting)
Search for more papers by this authorJenny Jiang MA
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (supporting), Investigation (supporting), Methodology (supporting), Writing - review & editing (supporting)
Search for more papers by this authorWendy G. Halpern DVM, PhD
Department of Pathology, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (supporting)
Search for more papers by this authorVeronica G. Anania PhD
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Formal analysis (equal), Funding acquisition (equal), Investigation (equal), Project administration (equal), Writing - original draft (equal)
Search for more papers by this authorJacqueline M. McBride PhD
Biomarker Development, Genentech, Inc., South San Francisco, California, USA
Contribution: Conceptualization (equal), Funding acquisition (lead), Project administration (lead), Resources (equal), Supervision (equal), Writing - original draft (equal)
Search for more papers by this authorCorresponding Author
Carrie M. Rosenberger PhD
Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA
Carrie Rosenberger and Adrienne Randolph contributed equally as senior authors.
Correspondence Adrienne Randolph, Division of Critical Care Medicine, Boston Children's Hospital, 300 Longwood Ave, Bader 634, Boston, MA 02115, USA.
Email: [email protected]
Carrie Rosenberger, PhD, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Funding acquisition (equal), Methodology (equal), Project administration (equal), Resources (lead), Supervision (lead), Writing - original draft (lead)
Search for more papers by this authorCorresponding Author
Adrienne G. Randolph MD
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA
Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Correspondence Adrienne Randolph, Division of Critical Care Medicine, Boston Children's Hospital, 300 Longwood Ave, Bader 634, Boston, MA 02115, USA.
Email: [email protected]
Carrie Rosenberger, PhD, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (equal), Funding acquisition (lead), Investigation (lead), Methodology (lead), Project administration (lead), Supervision (lead), Writing - original draft (lead), Writing - review & editing (lead)
Search for more papers by this authorThe Pediatric Intensive Care Influenza (PICFLU) Investigators
Group coauthors listed in the acknowledgments.
Search for more papers by this authorAbstract
Background
Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes.
Methods
We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D, and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality.
Results
Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza-infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes.
Conclusions
SP-D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
DATA AVAILABILITY STATEMENT
Deidentified data are available from the investigators through collaboration with the primary authors.
Supporting Information
| Filename | Description |
|---|---|
| ppul25776-sup-0001-SurfactantFluManuscript_Influenza_Supplemental_Materials.docx17.6 KB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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