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 (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.

Keywords: ARDS; biomarker; critical illness; length of mechanical ventilation; mortality; outcome; pediatric ARDS; pediatrics; surfactant.

Figure 1

Surfactant protein-D levels across primary diagnoses. Plasma SP-D levels are significantly different across primary diagnoses (P < .0001, determined using Kruskal-Wallis test). Plasma SP-D is significantly higher in patients with pneumonia compared with those with a primary diagnosis of asthma and significantly higher in the “Other” group compared with those with a primary diagnosis of asthma or bronchiolitis. The diagnoses of those in the “Other” group and the corresponding median SP-D are shown in e-Figure 1. ∗P < .05, Dunn’s Multiple Comparisons test. The number within the bars is the number of patients in each group. SP-D = surfactant protein D.

Figure 2

Surfactant protein-D levels in the absence of PARDS and across PARDS severities. Plasma SP-D levels are significantly different between patients without PARDS and different PARDS severity levels (P = .003 determined using using Kruskal-Wallis test). Plasma SP-D is significantly higher in patients with severe PARDS compared with those with no PARDS or mild PARDS (∗P < .05, Dunn’s Multiple Comparisons test). The number within the bars is the number of patients in each group. PARDS = pediatric ARDS. See Figure 1 legend for expansion of other abbreviation.

Figure 3

Surfactant protein-D levels in survivors and nonsurvivors. Plasma SP-D levels are significantly higher in patients who died (∗P < .001, Wilcoxon Two-Sample test). The number within the bars is the number of patients in each group. See Figures 1 and 2 legends for expansions of abbreviations.