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Review
. 2010 Jul 9;70(10):1255-82.
doi: 10.2165/10898570-000000000-00000.

Pharmacotherapy for prevention and treatment of acute respiratory distress syndrome: current and experimental approaches

Karen J Bosma  1 , Ravi Taneja, James F Lewis
Affiliations
Review

Pharmacotherapy for prevention and treatment of acute respiratory distress syndrome: current and experimental approaches

Karen J Bosma et al. Drugs. .

Abstract

The acute respiratory distress syndrome (ARDS) arises from direct and indirect injury to the lungs and results in a life-threatening form of respiratory failure in a heterogeneous, critically ill patient population. Critical care technologies used to support patients with ARDS, including strategies for mechanical ventilation, have resulted in improved outcomes in the last decade. However, there is still a need for effective pharmacotherapies to treat ARDS, as mortality rates remain high. To date, no single pharmacotherapy has proven effective in decreasing mortality in adult patients with ARDS, although exogenous surfactant replacement has been shown to reduce mortality in the paediatric population with ARDS from direct causes. Several promising therapies are currently being investigated in preclinical and clinical trials for treatment of ARDS in its acute and subacute, exudative phases. These include exogenous surfactant therapy, beta(2)-adrenergic receptor agonists, antioxidants, immunomodulating agents and HMG-CoA reductase inhibitors (statins). Recent research has also focused on prevention of acute lung injury and acute respiratory distress in patients at risk. Drugs such as captopril, rosiglitazone and incyclinide (COL-3), a tetracycline derivative, have shown promising results in animal models, but have not yet been tested clinically. Further research is needed to discover therapies to treat ARDS in its late, fibroproliferative phase. Given the vast number of negative clinical trials to date, it is unlikely that a single pharmacotherapy will effectively treat all patients with ARDS from differing causes. Future randomized controlled trials should target specific, more homogeneous subgroups of patients for single or combination therapy.

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Figures

Table I
Table I
Direct and indirect causes of acute lung injury/acute respiratory distress syndrome
Fig. 1
Fig. 1
‘Multiple hit’ theory of acute respiratory distress syndrome (ARDS) progression. The ‘first hit’ to the lung incites a pulmonary inflammatory response, which, when coupled with repeated ‘hits’ to the lung from injurious mechanical ventilation or other secondary insults, may lead to the pathological manifestations of ARDS. The most common cause of death in ARDS is multiple organ dysfunction syndrome (reproduced from Bosma et al.[7] [2007], with permission).
Table II
Table II
Pathophysiology of acute respiratory distress syndrome (ARDS)a
Fig. 2
Fig. 2
Progression of acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Initially, inflammatory damage to the alveolar-capillary barrier results in increased vascular permeability, leading to interstitial and alveolar oedema as proteinaceous fluid fills the alveolar space. There, the proteinaceous fluid interferes with the function and metabolism of the endogenous surfactant system. Coupled with this, neutrophils that infiltrate lungs are subsequently activated and represent an important source of inflammatory mediators and oxygen free radicals, inducing further epithelial and endothelial cell damage and an altered host immune response. Newly secreted mediators and/or spill-over of inflammatory mediators from the lung into the systemic circulation ultimately contribute to the development of MOF. Inflammatory mediators released from organs such as the liver, heart and kidney return to the lung via the systemic circulation and may contribute to further pulmonary inflammation. Thus, each new insult to the pulmonary system accelerates the acute lung injury cycle (reproduced from Bosma et al.[7] [2007], with permission).
Table III
Table III
Clinical trial acronyms
Table IV
Table IV
Pharmacotherapy studied for prevention or treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)a
Table IV
Table IV
Pharmacotherapy studied for prevention or treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)a
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