Table 1.

Emerging therapies for the prevention of ARDS and previous studies.

Medication	Mechanism of action	Animal Studies	Human Studies
Aspirin	Inhibition of platelet mediated cyclooxygenase metabolism involved in platelet-neutrophil-endothelial interactions.	Mice treated with aspirin have less pulmonary platelet and neutrophil sequestration. Also treated animals have improved survival and decreased lung weights.	Observational studies conflicting in terms of their findings. The largest cohort found a non-significant trend toward a protective effect. LIPS-A trial completed, awaiting results.
Systemic Corticosteroids	Multi-potent; inhibit inflammatory cytokines; induced apoptosis of macrophages; maintain endothelial cellular barrier.	Majority show improvement of hypoxemia, pulmonary vascular pressure and extra-vascular lung water.	Studies performed in the 1980s in heterogenous groups of patients showed no benefit in administering high-dose steroids. Subgroup analysis of RCT suggest using biomarkers may help with patient selection.
Inhaled Heparin	In addition to potentiating anti-thrombin-III, inhibits adhesion of neutrophils to endothelium and degrades intravascular and bronchial fibrin.	Conflicting results with improvement of hypoxemia histology scores and shunt fraction.	Suggest morbidity/mortality benefit in smoke inhalation injury patients; RCT currently enrolling patients.
Inhaled Corticosteroids	Same as systemic corticosteroids. In theory, might spare patients from hyperglycemia, myopathy, super-infection, etc.	Most studies conducted in mice indicate that physiological surrogates are improved by treatment prior to or after direct/indirect lung injury.	Subgroup analysis of LIPS-A cohort suggest protective effect of baseline ICS against development of ARDS. LIPS-B recruiting.
Inhaled Hypertonic Saline	Inhibition of neutrophil activation/chemotaxis and macrophage cytokine production	Rats with trauma show less pulmonary vascular permeability, neutrophil chemotaxis, matrix metalloprotease activity, IL-8 activity and ARDS at necroscopy.	Intravenous hypertonic saline shown to have no benefit in trauma patients, likely due to effects on coagulation cascade. Prospective study forthcoming from LIPS investigators.
Inhaled beta-agonists	Enhanced alveolar fluid clearance and inhibits neutrophil adhesion to the endothelium.	Improved pulmonary mechanics; decrease neutrophil sequestration, inflammatory cytokine concentrations and enhanced surfactant secretion.	LIPS-B ongoing; no difference in ARDS incidence but less pulmonary complications among high risk surgical patients, mainly pneumonia.
Statins	Decreases inflammatory cytokine levels, adhesion molecule expression, and neutrophil proliferation.	Improvement in oxygenation, hemodynamic surrogates, neutrophil sequestration and decreased cytokine concentration.	Human observational studies show inconsistent effects of prehospital statin use with regards to development of ARDS. Statin therapy for treatment of established ARDS has been shown to be ineffective.
Thrombolytic Therapy	More rapid resolution of pulmonary microthrombi	Rat studies showing mitigation of pulmonary microthrombus formation and decreased neutrophil chemotaxis	No human studies published to date
N-Acetyl Cysteine	Repletes intracellular stores of reduced glutathione, decreasing oxidative stress.	In vivo studies elucidating the mechanism of NAC.	Mitigated mortality and lung injury scores in patients with smoke inhalation injury.
Renin-angiotensin axis blockers	Angiotensin-2 positively modulates nuclear factor-κβ gene expression. ACE type 2 receptor with angiotensin as its ligand, prevents endothelial damage.	Effective in preventing endothelial damage and inflammatory cytokine expression.	Observational studies showed a protective effect among specific populations including Asians and diabetics
Peroxisome Proliferator Receptor agonists	Nuclear receptor superfamily related to the retinoid, steroid and thyroid receptors with three subtypes. They decrease inflammatory cytokine expression, neutrophil and macrophage chemotaxis plus inhibit oxidative burst in neutrophils.	Decreased wet to dry ratios, inflammatory cytokine expression and improved static compliance.	No human studies to date.
Curcumin	Up-regulation of PPAR-γ in various inflammatory cells (neutrophils, monocytes, T lymphocytes, endothelial and epithelial cells). Down-regulation of inflammatory transcription factors, enzymes and cytokines.	Decreased wet to dry ratios, and inflammatory cytokine secretion.	No human studies to date.