Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure-Practice Variations and Outcomes.

OBJECTIVE: Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High frequency ventilation was associated with an increased mean (SEM) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p \u3c 0.001) and an increased mean (SEM) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted

Understanding Conflict of Interest for Academic Entrepreneurs

A conflict of interest (COI) is defined as the presence of a risk for an undue influence on primary goals due to a secondary goal such as financial gain. Individuals must understand that the mere presence of the risk, and not the actual occurrence of the undue influence, constitutes a potential COI. In biomedical research, COI policies protect human subjects and research integrity while preserving public trust. Damage caused by actual research misconduct is severe and creates wide and long-lasting public mistrust. Thus, individuals should not view COI policies as burdensome and instead should consider them as preventative strategies that protect them from broader repercussions after a concern for research bias has been raised. The disclosure of individual financial relationships is a critical but limited first step in the process of identifying and managing COIs. The presence and severity of a COI in an individual’s disclosure are assessed by the insti­tution’s COI committee to determine appropriate strategies for the management of the COI, such as the need for more specific disclosure information, restriction of the individual’s role in the research, or even, in some circumstances, the elimination of a conflicting relationship

Administration of Drugs/Gene Products to the Respiratory System: A Historical Perspective of the Use of Inert Liquids

The present review is a historical perspective of methodology and applications using inert liquids for respiratory support and as a vehicle to deliver biological agents to the respiratory system. As such, the background of using oxygenated inert liquids (considered a drug when used in the lungs) opposed to an oxygen-nitrogen gas mixture for respiratory support is presented. The properties of these inert liquids and the mechanisms of gas exchange and lung function alterations using this technology are described. In addition, published preclinical and clinical trial results are discussed with respect to treatment modalities for respiratory diseases. Finally, this forward-looking review provides a comprehensive overview of potential methods for administration of drugs/gene products to the respiratory system and potential biomedical applications.</jats:p

Inhibition of β-catenin signaling improves alveolarization and reduces pulmonary hypertension in experimental bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of preterm infants. The development of pulmonary hypertension (PH) significantly increases the mortality and morbidity of this disease. β-Catenin signaling plays an important role in tissue development and remodeling. Aberrant β-catenin signaling is associated with clinical and experiment models of BPD. To test the hypothesis that inhibition of β-catenin signaling is beneficial in promoting alveolar and vascular development and preventing PH in experimental BPD, we examined the effects of ICG001, a newly developed pharmacological inhibitor of β-catenin, in preventing hyperoxia-induced BPD in neonatal rats. Newborn rat pups were randomized at postnatal day (P)2 to room air (RA) + DMSO (placebo), RA + ICG001, 90% FiO2 (O2) + DMSO, or O2 + ICG001. ICG001 (10 mg/kg) or DMSO was given by daily intraperitoneal injection for 14 days during continuous exposure to RA or hyperoxia. Primary human pulmonary arterial smooth muscle cells (PASMCs) were cultured in RA or hyperoxia (95% O2) in the presence of DMSO or ICG001 for 24 to 72 hours. Treatment with ICG001 significantly increased alveolarization and reduced pulmonary vascular remodeling and PH during hyperoxia. Furthermore, administering ICG001 decreased PASMC proliferation and expression of extracellular matrix remodeling molecules in vitro under hyperoxia. Finally, these structural, cellular, and molecular effects of ICG001 were associated with down-regulation of multiple β-catenin target genes. These data indicate that β-catenin signaling mediates hyperoxia-induced alveolar impairment and PH in neonatal animals. Targeting β-catenin may provide a novel strategy to alleviate BPD in preterm infants