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Circulating Surfactant Protein-D for Risk Stratification in Paediatric Acute Lung Infections: A Systematic Review
Ramona Chelcea1, Ioana Mihaiela Ciuca2, Naresh Reddy Mudireddy3
1Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania.
Insights
Elevated surfactant protein-D (SP-D) in children with lung infections indicates severe disease and predicts worse outcomes. Further validation is needed, but SP-D shows promise for risk stratification in pediatric pneumonia and viral lung injury.
Area of Science:
- Pediatric Pulmonology
- Biomarkers in Infectious Disease
- Critical Care Medicine
Background:
- Surfactant protein-D (SP-D) is released into circulation upon injury to the alveolo-capillary barrier.
- Acute infectious lung diseases in children can compromise this barrier, leading to SP-D release.
Purpose of the Study:
- To synthesize evidence on the diagnostic and prognostic performance of circulating SP-D in children with acute infectious lung disease.
- To evaluate SP-D's role in differentiating disease severity and predicting outcomes in pediatric respiratory infections.
Main Methods:
- Systematic literature search of MEDLINE, Embase, and Scopus (inception-June 1, 2025) for human studies.
- Inclusion of studies on pediatric patients (<18 years) with community-acquired pneumonia (CAP), viral pneumonitis, or pediatric acute respiratory distress syndrome (PARDS).
- Narrative synthesis due to heterogeneity in assays and outcome definitions; risk of bias assessed using ROBINS-I.
Main Results:
- Five studies (n=723) reported higher admission SP-D levels in severe CAP (AUCs 0.699-0.802).
- SP-D thresholds (110-180 ng/mL) showed sensitivities of 67-85% and specificities of 45-70%.
- SP-D correlated with ventilator days (r≈0.45) and ICU stay (r≈0.44) in influenza-associated respiratory failure; each 10 ng/mL increase in SP-D associated with higher odds of severe PARDS and death (aOR 1.02).
Conclusions:
- Elevated circulating SP-D correlates with disease severity, radiographic findings, and adverse short-term outcomes in pediatric lung infections.
- SP-D shows potential as a biomarker for risk stratification in childhood pneumonia and viral lung injury.
- Assay standardization and external validation are recommended for clinical integration of SP-D into multiparametric risk algorithms.
Abstract:
Background and Objectives: Surfactant protein-D (SP-D) enters the circulation when the alveolo-capillary barrier is injured. We synthesised evidence on the diagnostic and prognostic performance of circulating SP-D in children with acute infectious lung disease. Methods: We searched MEDLINE, Embase and Scopus (inception-1 June 2025) for human studies reporting serum/plasma SP-D in patients <18 years with community-acquired pneumonia (CAP), viral pneumonitis or paediatric ARDS (PARDS). Two reviewers independently screened, extracted data and assessed risk of bias (ROBINS-I). Primary outcomes were discrimination of severe versus non-severe disease and prediction of hard outcomes (mechanical ventilation, PARDS and mortality). Heterogeneity in assays and outcome definitions precluded meta-analysis; a narrative synthesis was undertaken. Results: Five studies (n = 723) from emergency and PICU settings met inclusion criteria. Admission SP-D was consistently higher in severe versus mild CAP; reported AUCs ranged 0.699-0.802. Thresholds of 110-180 ng/mL yielded sensitivities of 67-85% and specificities of 45-70%. In influenza-associated respiratory failure, SP-D correlated with ventilator days (r ≈ 0.45) and ICU length of stay (r ≈ 0.44). In multicentre PARDS cohorts, each 10 ng/mL increase in SP-D was associated with higher odds of severe PARDS and death (adjusted OR 1.02 per 10 ng/mL). Overall risk of bias across studies was low-to-moderate, with one study rated serious due to sampling and adjustment limitations. Conclusions: Across pathogens and care settings, elevated circulating SP-D correlates with radiographic consolidation, evolving PARDS and worse short-term outcomes. Although assay standardisation and external validation are needed, current evidence supports incorporating SP-D into multiparametric, age-aware risk-stratification algorithms for childhood pneumonia and viral lung injury.
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