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Table 1 Emerging therapies for smoke inhalation injury

From: Emerging therapies for smoke inhalation injury: a review

Therapeutic strategy Type of therapeutic Model Animal Route of administration Results
Stem cell Bone marrow derived mesenchymal stem cells Smoke inhalation
Smoke inhalation
Smoke inhalation
Smoke inhalation
Smoke inhalation
Rabbit [7] IV, marginal ear vein Decreased VEGF
Decreased total lung water content
    Rabbit [14, 15] IV, marginal ear vein Decreased pro-inflammatory cytokines in serum, increased anti-inflammatory cytokines in serum
Improved histopathology
Decreased wet-to-dry ratio
    Rat [12] IV, tail vein Decreased wet-to-dry ratio
Decreased IL-8
Increased IL-10
    Rat [13] IV, tail vein Decreased wet-to-dry ratio
Improved histopathology
    Mouse [16] IV, tail vein Decreased levels of TNF-alpha
Increased migration of stem cells to lung tissue in injured mice
  Human amnion mesenchymal stem cells Smoke inhalation Rat [18] IV, tail vein Decreased wet-to-dry ratio
Improved histopathology
Improved oxygenation
Increased surfactant levels
  Adipose derived mesenchymal stem cells Smoke inhalation Sheep [19] IV, central venous infusion Decreased pulmonary vascular permeability
Decreased wet-to-dry ratio
Improved oxygenation
Anticoagulants Tissue plasminogen activator Burn and smoke inhalation Sheep [23] Aerosolized Improved airway obstruction
Decreased wet-to-dry ration
Improved vascular leakage
  Antithrombin III/heparin Burn and smoke inhalation Sheep [24]
Sheep [25]
Combined aerosolized
IV infusion- ATIII
Aerosolized- heparin
Improved airway obstruction
Improved pulmonary mechanics and oxygenation
Decreased wet-to-dry ratio
Selectin inhibition P selectin Burn and smoke inhalation Sheep [26] IV injection No pulmonary protection in injury vs. control
  L selectin Burn and smoke inhalation Sheep [28] IV injection before injury Improved microvascular permeability
No significant improvement in oxygenation
    Sheep [27] IV injection after injury Decreased systemic neutrophil infiltration
Improved vascular permeability
Decreased pulmonary edema
Immunomodulation CXCL-1 neutralization Burn and smoke inhalation Mouse [30] IV, tail vein Improved lung histopathology
Decreased wet-to-dry ratio
Decreased pro inflammatory cytokines
Decreased pulmonary neutrophil infiltration
  Puerarin Smoke inhalation Rat [31] IP injection Improved lung histopathology
Decreased neutrophil infiltration
Decreased pulmonary vascular permeability
  Perfluorohexane Burn and smoke inhalation Human [32] (RCT) Intratracheal instillation Improved pulmonary mechanics and oxygenation
Decreased neutrophil infiltration
Decreased pro inflammatory cytokines
  SOCS-1 Smoke inhalation Mouse [37] Intratracheal instillation Improved mortality
Improved lung histopathology
Decreased pro inflammatory cytokines
  Glutamine Smoke inhalation Rat [44] IV, tail vein Decreased pulmonary edema
Decreased pro inflammatory cytokines
Improved histopathology
Decreased fibrosis
Increased levels of protective heat shock proteins
Recombinant superoxide dismutase Manganese superoxide dismutase Smoke inhalation
Smoke inhalation
Sheep [51] IV bolus No significant change in oxygenation or lung lymph flow
    Sheep [52] Aerosolized No significant change in oxygenation or wet-to-dry ratio
Decreased conjugated dienes
Peroxynitrite decomposition catalyst W-85 Burn and smoke inhalation Sheep [54] Intra-arterial injection, bronchial artery Improved pulmonary oxygenation
Decreased pulmonary vascular permeability
  INO-4885 Burn and smoke inhalation Sheep [55] IV bolus followed by infusion Improved oxygenation and pulmonary mechanics
Decreased pulmonary edema
Decreased pro inflammatory cytokines
Decreased VEGF, PARP
  R-100 Smoke inhalation, bacterial injury Sheep [56] IV bolus followed by infusion Improved oxygenation and pulmonary mechanics
No change in histopathology or wet-to-dry ratio
iNOS inhibition MEG Burn and smoke inhalation Sheep [87] IV infusion Increased iNOS levels in treatment groups
Decreased pulmonary edema
Improved pulmonary vascular permeability
  BBS-2 (48 h) Burn and smoke inhalation Sheep [5Improved lung histopathology Decreased ROS, lipid peroxidation, acetylcholine esterase activity
7]
IV infusion, 48 h Improved 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 inhalation Sheep [48] IV infusion, 24 h Improved pulmonary gas exchange
Improved airway mechanics
Decreased pulmonary edema
  BME Smoke inhalation Rat [58] Oral Decreased levels of nitrite, nitrate, PARP, NF-kappa B, and neutrophil infiltration
nNOS inhibition 7-nitroindazole (7-NI) Burn and smoke inhalation Sheep [60] IV infusion, 24 h Decreased levels of PARP, pro-inflammatory cytokine IL-8, neutrophil infiltration
Improved airway obstruction
Improved oxygenation
Combined nNOS and iNOS inhibition 7-NI→BBS-2 Smoke inhalation and bacterial instillation Sheep [61] IV infusion, 12 h of 7-NI followed by 12 h of BBS-2 Improved airway obstruction
Improved pulmonary gas exchange
Decreased pulmonary VEGF, PARP, 3-NT
No change in pulmonary edema
  7-NI+BBS-2 Burn and smoke inhalation Sheep [62] IV infusion, combined Improved pulmonary oxygenation and mechanics
Decreased lung lymph flow
Decreased pulmonary edema
Hydrogen sulfide H2S Smoke inhalation Rat [67] Aerosolized Decreased MDA, NO, iNOS, and NF-kappa B levels
Improved oxidative stress
  Sodium sulfide Burn and smoke inhalation Mouse [68] Subcutaneous injection Decreased mortality
Decreased pro inflammatory IL-1 beta, increased anti-inflammatory IL-10
Improved pulmonary histopathology
  Sodium sulfide Burn and smoke inhalation Sheep [69] Bolus and IV infusion, 24 h Decreased mortality
Improved pulmonary oxygenation and mechanics
Decreased pulmonary edema
Decreased protein oxidation
HMG-CoA reductase inhibition Simvastatin Burn and smoke inhalation Rat [72] Oral Decreased iNOS
Reduction of pulmonary apoptosis
Improved pulmonary histopathology
Proton pump inhibition Esomeprazole Smoke inhalation Mouse [73] Oral Decreased levels of iNOS
Decreased fibrosis
Decreased plasma levels of pro inflammatory cytokine TNF-alpha
Solid lipid nanoparticles Carvacrol Smoke inhalation Rat [86] Aerosolized Improved histopathology, Decreased oxidative injury (although also seen in oxygen treated groups)
No change to myeloperoxidase levels