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 |
| Â | Â | Â | IV, marginal ear vein | Decreased pro-inflammatory cytokines in serum, increased anti-inflammatory cytokines in serum Improved histopathology Decreased wet-to-dry ratio | |
| Â | Â | Â | Rat [12] | IV, tail vein | Decreased wet-to-dry ratio Decreased IL-8 Increased IL-10 |
| Â | Â | Â | Rat [13] | IV, tail vein | Decreased wet-to-dry ratio Improved histopathology |
| Â | Â | Â | Mouse [16] | IV, tail vein | Decreased levels of TNF-alpha Increased migration of stem cells to lung tissue in injured mice |
| Â | Human amnion mesenchymal stem cells | Smoke inhalation | Rat [18] | IV, tail vein | Decreased wet-to-dry ratio Improved histopathology Improved oxygenation Increased surfactant levels |
| Â | 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 |
| Â | 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 |
| Â | L selectin | Burn and smoke inhalation | Sheep [28] | IV injection before injury | Improved microvascular permeability No significant improvement in oxygenation |
| Â | Â | Â | 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 |
| Â | Puerarin | Smoke inhalation | Rat [31] | IP injection | Improved lung histopathology Decreased neutrophil infiltration Decreased pulmonary vascular permeability |
| Â | Perfluorohexane | Burn and smoke inhalation | Human [32] (RCT) | Intratracheal instillation | Improved pulmonary mechanics and oxygenation Decreased neutrophil infiltration Decreased pro inflammatory cytokines |
| Â | SOCS-1 | Smoke inhalation | Mouse [37] | Intratracheal instillation | Improved mortality Improved lung histopathology Decreased pro inflammatory cytokines |
| Â | 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 |
| Â | Â | Â | 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 |
| Â | 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 |
| Â | 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 |
| Â | 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 |
| Â | BBS-2 (24 h) | Burn and smoke inhalation | Sheep [48] | IV infusion, 24 h | Improved pulmonary gas exchange Improved airway mechanics Decreased pulmonary edema |
| Â | 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 |
| Â | 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 |
| Â | 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 |
| Â | 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 |