Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide

Abstract

BackgroundVentilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing.MethodsWithin a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation. TA was collected from 43 premature infants randomly assigned to receive either iNO or placebo gas (birth weight 530–1230 g, median 800 g, gestational age 24 to 28 2/7 weeks, median 26 weeks). Interleukin (IL)-1β, IL-6, IL-8, transforming growth factor (TGF)-β1, interferon γ-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, acid sphingomyelinase (ASM), neuropeptide Y and leukotriene B4 were measured in serial TA samples from postnatal day 2 to 14. Furthermore, TA levels of nitrotyrosine and nitrite were determined under iNO therapy.ResultsThe TA levels of IP-10, IL-6, IL-8, MIP-1α, IL-1β, ASM and albumin increased with advancing postnatal age in critically ill preterm infants, whereas nitrotyrosine TA levels declined in both, iNO-treated and placebo-treated infants. The iNO treatment generally increased nitrite TA levels, whereas nitrotyrosine TA levels were not affected by iNO treatment. Furthermore, iNO treatment transiently reduced early inflammatory and fibrotic markers associated with BPD development including TGF-β1, IP-10 and IL-8, but induced a delayed increase of ASM TA levels.ConclusionTreatment with iNO may have played a role in reducing several inflammatory and fibrotic mediators in TA of preterm infants compared to placebo-treated infants. However, survival without BPD was not affected in the main EUNO trial.Trial registrationNCT00551642

Effects of inhaled nitric oxide for postoperative hypoxemia in acute type A aortic dissection: a retrospective observational study

“…During iNO treatment, routine MetHb and exhaled NO 2 monitoring are required. With low-dose iNO, the concentrations of those two substances are small and stable; their safety has been confirmed in other studies of iNO in infants [22]. Another possible side-effect of iNO is that it can inhibit platelet aggregation and adhesion to the vascular endothelium, thereby prolonging bleeding time.…”

“…Studies in different animal models have demonstrated that iNO ameliorates lung injury by inhibiting inflammatory cytokines and oxidative damage [19][20][21]. A recent study on iNO-mediated prevention of bronchopulmonary dysplasia in Europe showed that iNO treatment may decrease several inflammatory and fibrotic factors in the lungs [22]. Preemptive iNO in human liver transplantation surgery led to clear anti-inflammatory effects in liver grafts which protected graft function, ameliorated pathological changes, and reduced postoperative morbidity [23].…”

Ceramide and Regulation of Vascular Tone

“…These studies consistently reported an increased in the levels of ceramide in tracheal aspirates in pediatric patients undergoing mechanical ventilation [172,173]. However, ceramide production tends to increase with postnatal development and this increase shows no or even a negative correlation with long term complications [171,172].…”

Prevention of Oxygen-Induced Inflammatory Lung Injury by Caffeine in Neonatal Rats

“…Baro- and volutrauma and oxygen toxicity are thought to be the main triggers [ 8 ]. Morphological changes due to oxidative stress result in the disruption of lung development [ 27 ], accompanied by increased proinflammatory cytokine and chemokine expression and immune cell infiltration in lung tissue [ 28 – 30 ]. Apoptosis and proliferation play an important role in normal cell turnover and tissue development.…”