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Published on: April 7, 2021
Surfactant protein D is a biomarker of influenza-related pediatric lung injury
Arindam Chakrabarti1, Allen Nguyen2, Margaret M Newhams3
1Biomarker Discovery, Genentech, Inc., South San Francisco, California, USA.
Insights
Surfactant protein D (SP-D) may help identify children with severe influenza lung infections. However, bacterial pneumonia can affect SP-D
Area of Science:
- Pediatric Pulmonology
- Infectious Diseases
- Biomarker Discovery
Background:
- Influenza virus lower respiratory infections in children can lead to severe lung damage.
- Identifying biomarkers for risk stratification is crucial for targeted interventions.
- Early detection of lung injury may predict worse outcomes.
Purpose of the Study:
- To evaluate surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16) as biomarkers in children with influenza-associated acute respiratory failure.
- To assess the relationship between these protein levels and disease severity.
Main Methods:
- A mouse model of influenza infection was used to study lung pathophysiology.
- Plasma levels of SP-D, SP-A, and CC16 were measured in 94 children with influenza-associated acute respiratory failure (PICFLU cohort).
- Associations between protein levels and clinical outcomes (e.g., ARDS, mechanical ventilation, ICU days) were analyzed.
Main Results:
- In mice, SP-D increased with alveolar-vascular permeability after influenza infection.
- In children, higher SP-D levels correlated with moderate-severe ARDS, mechanical ventilation, and longer hospital/ICU stays, particularly without bacterial coinfection.
- SP-D levels were lower in children with secondary bacterial pneumonia and did not correlate with outcomes in this subgroup.
Conclusions:
- SP-D shows potential as an early circulating biomarker for influenza-induced lung damage in children.
- The presence of secondary bacterial pneumonia can impact the performance of SP-D as a biomarker.
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.
