Understanding Gene Therapy in Acute Respiratory Distress Syndrome

2019 ◽  
Vol 19 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Xue-Peng Zhang ◽  
Wei-Tao Zhang ◽  
Yue Qiu ◽  
Min-Jie Ju ◽  
Guo-Wei Tu ◽  
...  

Acute Respiratory Distress Syndrome (ARDS) and its complications remain lifethreatening conditions for critically ill patients. The present therapeutic strategies such as prone positioning ventilation strategies, nitric oxide inhalation, restrictive intravenous fluid management, and extracorporeal membrane oxygenation (ECMO) do not contribute much to improving the mortality of ARDS. The advanced understanding of the pathophysiology of acute respiratory distress syndrome suggests that gene-based therapy may be an innovative method for this disease. Many scientists have made beneficial attempts to regulate the immune response genes of ARDS, maintain the normal functions of alveolar epithelial cells and endothelial cells, and inhibit the fibrosis and proliferation of ARDS. Limitations to effective pulmonary gene therapy still exist, including the security of viral vectors and the pulmonary defense mechanisms against inhaled particles. Here, we summarize and review the mechanism of gene therapy for acute respiratory distress syndrome and its application.

2019 ◽  
Vol 32 (3) ◽  
pp. 347-360 ◽  
Author(s):  
Mitchell S. Buckley ◽  
Amy L. Dzierba ◽  
Justin Muir ◽  
Jeffrey P. Gonzales

Acute respiratory distress syndrome (ARDS) remains a common complication associated with significant negative outcomes in critically ill patients. Lung-protective mechanical ventilation strategies remain the cornerstone in the management of ARDS. Several therapeutic options are currently available including fluid management, neuromuscular blocking agents, prone positioning, extracorporeal membrane oxygenation, corticosteroids, and inhaled pulmonary vasodilating agents (prostacyclins and nitric oxide). Unfortunately, an evidence-based, standard-of-care approach in managing ARDS beyond lung-protective ventilation remains elusive, contributing to significant variability in clinical practice. Although the optimal therapeutic strategy for managing moderate to severe ARDS remains extremely controversial, therapies supported with more robust clinical evidence should be considered first. The purpose of this narrative review is to discuss the published clinical evidence for both pharmacologic and nonpharmacologic management strategies in adult patients with moderate to severe ARDS as well as to discuss practical considerations for implementation.


2015 ◽  
Vol 59 (6) ◽  
pp. 256
Author(s):  
Colin K. Grissom ◽  
Eliotte L. Hirshberg ◽  
Justin B. Dickerson ◽  
Samuel M. Brown ◽  
Michael J. Lanspa ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Jing Liu ◽  
David A. Dean

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.


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