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Table 1 Emerging therapies for smoke inhalation injury

From: Emerging therapies for smoke inhalation injury: a review

Therapeutic strategyType of therapeuticModelAnimalRoute of administrationResults
Stem cellBone marrow derived mesenchymal stem cellsSmoke inhalation
Smoke inhalation
Smoke inhalation
Smoke inhalation
Smoke inhalation
Rabbit [7]IV, marginal ear veinDecreased VEGF
Decreased total lung water content
   Rabbit [14, 15]IV, marginal ear veinDecreased pro-inflammatory cytokines in serum, increased anti-inflammatory cytokines in serum
Improved histopathology
Decreased wet-to-dry ratio
   Rat [12]IV, tail veinDecreased wet-to-dry ratio
Decreased IL-8
Increased IL-10
   Rat [13]IV, tail veinDecreased wet-to-dry ratio
Improved histopathology
   Mouse [16]IV, tail veinDecreased levels of TNF-alpha
Increased migration of stem cells to lung tissue in injured mice
 Human amnion mesenchymal stem cellsSmoke inhalationRat [18]IV, tail veinDecreased wet-to-dry ratio
Improved histopathology
Improved oxygenation
Increased surfactant levels
 Adipose derived mesenchymal stem cellsSmoke inhalationSheep [19]IV, central venous infusionDecreased pulmonary vascular permeability
Decreased wet-to-dry ratio
Improved oxygenation
AnticoagulantsTissue plasminogen activatorBurn and smoke inhalationSheep [23]AerosolizedImproved airway obstruction
Decreased wet-to-dry ration
Improved vascular leakage
 Antithrombin III/heparinBurn and smoke inhalationSheep [24]
Sheep [25]
Combined aerosolized
IV infusion- ATIII
Aerosolized- heparin
Improved airway obstruction
Improved pulmonary mechanics and oxygenation
Decreased wet-to-dry ratio
Selectin inhibitionP selectinBurn and smoke inhalationSheep [26]IV injectionNo pulmonary protection in injury vs. control
 L selectinBurn and smoke inhalationSheep [28]IV injection before injuryImproved microvascular permeability
No significant improvement in oxygenation
   Sheep [27]IV injection after injuryDecreased systemic neutrophil infiltration
Improved vascular permeability
Decreased pulmonary edema
ImmunomodulationCXCL-1 neutralizationBurn and smoke inhalationMouse [30]IV, tail veinImproved lung histopathology
Decreased wet-to-dry ratio
Decreased pro inflammatory cytokines
Decreased pulmonary neutrophil infiltration
 PuerarinSmoke inhalationRat [31]IP injectionImproved lung histopathology
Decreased neutrophil infiltration
Decreased pulmonary vascular permeability
 PerfluorohexaneBurn and smoke inhalationHuman [32] (RCT)Intratracheal instillationImproved pulmonary mechanics and oxygenation
Decreased neutrophil infiltration
Decreased pro inflammatory cytokines
 SOCS-1Smoke inhalationMouse [37]Intratracheal instillationImproved mortality
Improved lung histopathology
Decreased pro inflammatory cytokines
 GlutamineSmoke inhalationRat [44]IV, tail veinDecreased pulmonary edema
Decreased pro inflammatory cytokines
Improved histopathology
Decreased fibrosis
Increased levels of protective heat shock proteins
Recombinant superoxide dismutaseManganese superoxide dismutaseSmoke inhalation
Smoke inhalation
Sheep [51]IV bolusNo significant change in oxygenation or lung lymph flow
   Sheep [52]AerosolizedNo significant change in oxygenation or wet-to-dry ratio
Decreased conjugated dienes
Peroxynitrite decomposition catalystW-85Burn and smoke inhalationSheep [54]Intra-arterial injection, bronchial arteryImproved pulmonary oxygenation
Decreased pulmonary vascular permeability
 INO-4885Burn and smoke inhalationSheep [55]IV bolus followed by infusionImproved oxygenation and pulmonary mechanics
Decreased pulmonary edema
Decreased pro inflammatory cytokines
Decreased VEGF, PARP
 R-100Smoke inhalation, bacterial injurySheep [56]IV bolus followed by infusionImproved oxygenation and pulmonary mechanics
No change in histopathology or wet-to-dry ratio
iNOS inhibitionMEGBurn and smoke inhalationSheep [87]IV infusionIncreased iNOS levels in treatment groups
Decreased pulmonary edema
Improved pulmonary vascular permeability
 BBS-2 (48 h)Burn and smoke inhalationSheep [5Improved lung histopathology Decreased ROS, lipid peroxidation, acetylcholine esterase activity
7]
IV infusion, 48 hImproved oxygenation and pulmonary mechanics
Decreased pulmonary shunt fraction
Improved lung lymph flow
Decreased pulmonary edema
Improved airway obstruction
 BBS-2 (24 h)Burn and smoke inhalationSheep [48]IV infusion, 24 hImproved pulmonary gas exchange
Improved airway mechanics
Decreased pulmonary edema
 BMESmoke inhalationRat [58]OralDecreased levels of nitrite, nitrate, PARP, NF-kappa B, and neutrophil infiltration
nNOS inhibition7-nitroindazole (7-NI)Burn and smoke inhalationSheep [60]IV infusion, 24 hDecreased levels of PARP, pro-inflammatory cytokine IL-8, neutrophil infiltration
Improved airway obstruction
Improved oxygenation
Combined nNOS and iNOS inhibition7-NI→BBS-2Smoke inhalation and bacterial instillationSheep [61]IV infusion, 12 h of 7-NI followed by 12 h of BBS-2Improved airway obstruction
Improved pulmonary gas exchange
Decreased pulmonary VEGF, PARP, 3-NT
No change in pulmonary edema
 7-NI+BBS-2Burn and smoke inhalationSheep [62]IV infusion, combinedImproved pulmonary oxygenation and mechanics
Decreased lung lymph flow
Decreased pulmonary edema
Hydrogen sulfideH2SSmoke inhalationRat [67]AerosolizedDecreased MDA, NO, iNOS, and NF-kappa B levels
Improved oxidative stress
 Sodium sulfideBurn and smoke inhalationMouse [68]Subcutaneous injectionDecreased mortality
Decreased pro inflammatory IL-1 beta, increased anti-inflammatory IL-10
Improved pulmonary histopathology
 Sodium sulfideBurn and smoke inhalationSheep [69]Bolus and IV infusion, 24 hDecreased mortality
Improved pulmonary oxygenation and mechanics
Decreased pulmonary edema
Decreased protein oxidation
HMG-CoA reductase inhibitionSimvastatinBurn and smoke inhalationRat [72]OralDecreased iNOS
Reduction of pulmonary apoptosis
Improved pulmonary histopathology
Proton pump inhibitionEsomeprazoleSmoke inhalationMouse [73]OralDecreased levels of iNOS
Decreased fibrosis
Decreased plasma levels of pro inflammatory cytokine TNF-alpha
Solid lipid nanoparticlesCarvacrolSmoke inhalationRat [86]AerosolizedImproved histopathology, Decreased oxidative injury (although also seen in oxygen treated groups)
No change to myeloperoxidase levels