title: Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS.
abstract: BACKGROUND
  Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants.
  
  
  METHODS
  Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination.
  
  
  RESULTS
  SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant.
  
  
  CONCLUSIONS
  These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant.
authors: Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. marla.wolfson@temple.edu
authors: Marla R
authors: MR
authors: Wolfson
authors: Jichuan
authors: J
authors: Wu
authors: Terrence L
authors: TL
authors: Hubert
authors: Timothy J
authors: TJ
authors: Gregory
authors: Jan
authors: J
authors: Mazela
authors: Thomas H
authors: TH
authors: Shaffer
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology*; D005865:Gestational Age; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011506:Proteins / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D012127:Respiratory Distress Syndrome, Newborn / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012756:Sheep; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D015415:Biomarkers; D004338:Drug Combinations; D005233:Fatty Alcohols; D018836:Inflammation Mediators; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011506:Proteins; D011663:Pulmonary Surfactants; C502722:lucinactant; C068291:poractant alfa; C072197:beractant