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Surfactant has been administered through endotracheal tubes and also under spontaneous breathing using feeding catheters. We asked if different tube diameters and temperature may affect the amount of surfactant effectively delivered to the lungs.Bench study using high-accuracy, legal balance and tube/catheters of different diameters. We injected 200 mg of poractant alfa into the tubes followed by air boluses. Experiments were performed in triplicate, both at room temperature and at 37°C. Surfactant and phospholipid remaining in the tube were calculated.Surfactant lost into thin catheters (11 ± 0.4%) was more than that in endotracheal tubes (2-mm diameter: 3.6 ± 1.4%; 2.5-mm diameter: 3.7 ± 0.2%; 3-mm diameter: 5.2 ± 0.4%; p0.001 at post hoc test in each comparison against the thin catheter). Similar findings were found at 37°C (2-mm tube: 3.4 ± 0.4%; 2.5-mm tube: 3.8 ± 0.2%; 3-mm tube: 3.6 ± 0.4%; feeding tube: 11.5 ± 0.6%; p0.001 as above). In terms of lost phospholipids, 23 ± 0.8 mg were lost in the feeding tubes; 7.2 ± 2.9 mg (2-mm diameter), 7.4 ± 0.4 mg (2.5-mm diameter), and 10.3 ± 0.9 mg (3-mm diameter) of phospholipids remained in endotracheal tubes (p0.001 in each comparison against the feeding tube).Surfactant loss using thin catheters is around two to three times higher than using common endotracheal tubes; on average, 20 mg of phospholipids (11% of the administered dose) are lost. These data may be useful to refine surfactant dosing.

Introduction Secretory phospholipase A2 is supposed to play a role in acute lung injury but no data are available for pediatric acute respiratory distress syndrome (ARDS). It is not clear which enzyme subtypes are secreted and what the relationships are between enzyme activity, biophysical and biochemical parameters, and clinical outcomes. We aimed to measure the enzyme and identify its subtypes and to study its biochemical and biophysical effect. The secondary aim was to correlate enzyme activity with clinical outcome. Methods Bronchoalveolar lavage was performed in 24 infants with ARDS and 14 controls with no lung disease. Samples were assayed for secretory phospholipase A2 and molecules related to its activity and expression. Western blotting and captive bubble surfactometry were also performed. Clinical data were real time downloaded. Results Tumor necrosis factor-α (814 (506-2,499) vs. 287 (111-1,315) pg/mL; P = 0.04), enzyme activity (430 (253-600) vs. 149 (61-387) IU/mL; P = 0.01), free fatty acids (4.3 (2.8-8.6) vs. 2 (0.8-4.6) mM; P = 0.026), and minimum surface tension (25.6 ± 6.1 vs. 18 ± 1.8 mN/m; P = 0.006) were higher in ARDS than in controls. Phospholipids are lower in ARDS than in controls (76.5 (54-100) vs. 1,094 (536-2,907) μg/mL; P = 0.0001). Three enzyme subtypes were identified (-IIA, -V, -X), although in lower quantities in controls; another subtype (-IB) was mainly detected in ARDS. Significant correlations exist between enzyme activity, free fatty acids (ρ = 0.823; P < 0.001), and surface tension (ρ = 0.55; P < 0.028). Correlations also exist with intensive care stay (ρ = 0.54; P = 0.001), PRISM-III24 (ρ = 0.79; P< 0.001), duration of ventilation (ρ = 0.53; P = 0.002), and oxygen therapy (ρ = 0.54; P = 0.001). Conclusions Secretory phospholipase A2 activity is raised in pediatric ARDS and constituted of four subtypes. Enzyme correlates with some inflammatory mediators, surface tension, and major clinical outcomes. Secretory phospholipase A2 may be a clinically relevant target in pediatric ARDS.

Acute lung injury is a life-threatening condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing. sPLA2 activity, free fatty acids, tumour necrosis factor-α (TNF-α) and protein concentrations were measured in culture supernatants. Treatment with varespladib (p=0.019) and varespladib + surfactant (p=0.013), reduced the enzyme activity by approximately 15% from the basal level measured in the untreated cultures. Surfactant, varespladib and varespladib + surfactant, respectively decreased free fatty acids by -45% (p=0.045), - 62% (p=0.009) and -48% (p=0.015), from the baseline concentration of the untreated cultures. Varespladib and poractant- α co-administration reduces sPLA2 activity and free fatty acids release in cultured rat alveolar macrophages, although a clear drug synergy was not evident. Since co-administration may be useful to reduce inflammation and surfactant inactivation in acute lung injury, further in vivo studies are warranted to verify its clinical usefulness.