Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening form of respiratory failure that affects a heterogeneous population of critically ill patients. Although overall mortality appears to be decreasing in recent years due to improvements in supportive care, there are presently no proven, effective pharmacological therapies to treat ARDS and prevent its associated complications. The most common cause of death in ARDS is not hypoxemia or pulmonary failure, but rather multiple organ dysfunction syndrome (MODS), suggesting that improving survival in patients with ARDS may be linked to decreasing the incidence or severity of MODS. The key to developing novel treatments depends, in part, on identifying and understanding the mechanisms by which ARDS leads to MODS, although the heterogeneity and complexity of this disorder certainly poses a challenge to investigators. Novel therapies in development for treatment of ALI/ARDS include exogenous surfactant, therapies aimed at modulating neutrophil activity, such as prostaglandin and complement inhibitors, and treatments targeting earlier resolution of ARDS, such as beta-agonists and granulocyte macrophage colony-stimulating factor. From a clinical perspective, identifying subpopulations of patients most likely to benefit from a particular therapy and recognising the appropriate stage of illness in which to initiate treatment could potentially lead to better outcomes in the short term.
Bosma
Karen J
KJ
University of Western Ontario, Division of Respirology, London Health Sciences Centre, University Hospital, 339 Windermere Road, London, Ontario, N6A 5A5, Canada. karenj.bosma@lhsc.on.ca
Lewis
James F
JF
D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D015195:Drug Design; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005466:Fluorocarbons / Q000627:therapeutic use; D006801:Humans; D006842:Hydrocarbons, Brominated; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use; D018579:Patient Selection; D011663:Pulmonary Surfactants / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015507:Drugs, Investigational; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D011663:Pulmonary Surfactants; D019141:Respiratory System Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; C003072:perflubron