Ventilator-induced lung injury increases proinflammatory cytokines in the adult lung. We asked if positive end-expiratory pressure (PEEP) affects proinflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 +/- 3 d gestation were treated with 100 mg/kg recombinant human surfactant protein-C surfactant and ventilated for 2 or 7 h with 0, 4, or 7 cm H(2)O of PEEP. Unventilated fetal lambs were used as controls. Within 2 h of ventilation, alveolar total protein and activated neutrophils were increased and expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was increased in lung tissue of all ventilated animals relative to unventilated controls. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals than 4 PEEP animals. IL-1beta, IL-6, and IL-8 mRNAs were significantly elevated in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage fractional area of collapsed alveoli was significantly higher for 0 PEEP compared with 4 and 7 PEEP groups. Mechanical ventilation increased the expression of proinflammatory mediators in surfactant-treated preterm lungs and the use of 4 PEEP minimized this response.

BackgroundAt birth, the majority of neonates born at <30 weeks of gestation require respiratory support to facilitate transition and ensure adequate gas exchange. Although the optimal approach to the initial respiratory management is uncertain, the American Academy of Pediatrics endorses noninvasive respiratory support with nasal continuous positive airway pressure (nCPAP) for premature neonates with respiratory insufficiency. Despite evidence for its use, nCPAP failure, requiring intubation and mechanical ventilation, is common. Recently, investigators have described a novel method to deliver bubble nCPAP, termed Seattle-PAP. While preclinical and pilot studies are encouraging regarding the potential value of Seattle-PAP, a large trial is needed to compare Seattle-PAP directly with the current standard of care for bubble nCPAP (Fisher & Paykel CPAP or FP-CPAP).Methods/designWe designed a multicenter, non-blinded, randomized controlled trial that will enroll 230 premature infants (220/7 to 296/7 weeks of gestation). Infants will be randomized to receive Seattle-PAP or FP-CPAP. The primary outcome is respiratory failure requiring intubation and mechanical ventilation. Secondary outcomes include measures of short- and long-term respiratory morbidity and cost-effectiveness.DiscussionThis trial will assess whether Seattle-PAP is more efficacious and cost-effective than FP-CPAP in real-world practice among premature neonates.Trial registrationClinicalTrials.gov, NCT03085329. Registered on 21 March 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3166-6) contains supplementary material, which is available to authorized users.

Objective To test the hypothesis that infants born <30 weeks' gestation supported by Seattle-PAP will have lower rates of continuous positive airway pressure (CPAP) failure than infants supported with conventional, Fisher&Paykel-CPAP (FP-CPAP). Study design Randomized trial (3/2017-01/2019) at 5 NICUs. The primary outcome was CPAP failure; subgroup analyses (gestational age, receipt antenatal corticosteroids) were performed. Results A total of 232 infants were randomized. Infants in the Seattle-PAP and FP-CPAP groups had mean gestational ages of 27.0 and 27.2 weeks, respectively. We observed no differences in rates of treatment failure between Seattle-PAP (40/112, 35.7%) and FP-CPAP (38/120, 31.7%; risk difference, 4.1%; 95% CI, −8.1-16.2; P = 0.51). Subgroup analysis indicated no differences in rates of CPAP failure. We observed no differences between the two groups in frequencies of adverse events or duration of respiratory support. Conclusions Among infants born <30 weeks' gestation, rates of CPAP failure did not differ between Seattle-PAP and FP-CPAP.