Limits...
Alcoholic lung disease.

Kershaw CD, Guidot DM - Alcohol Res Health (2008)

Bottom Line: This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality.However, there have been no systems biological approaches to the study of the alcoholic lung to date.However, the alcoholic lung represents a clear example of environment-host interactions that should be well suited for such applications.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia.

ABSTRACT
In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality. Experimental and clinical studies are shedding light on the basic mechanisms by which alcohol abuse predisposes some people to both acute lung injury and pneumonia. At the same time, novel therapeutic targets could be utilized in treating these uniquely vulnerable people. However, there have been no systems biological approaches to the study of the alcoholic lung to date. This is in part because the association between alcohol abuse and acute lung injury was made relatively recently and remains largely unrecognized, even by lung researchers. In parallel, efforts to study complex diseases such as acute lung injury and pneumonia using a genomics and/or proteomics approach, which involves the study of an organism's genes and/or proteins, still are in their infancy. However, the alcoholic lung represents a clear example of environment-host interactions that should be well suited for such applications.

Show MeSH

Related in: MedlinePlus

Proposed pathophysiological sequence by which alcohol abuse renders the lung susceptible during acute inflammatory stresses such as infection (i.e., sepsis) and trauma. Alcohol abuse activates the renin-angiotensin system1 which, via its active mediator angiotensin II, increases the expression and activity of the enzyme NADPH oxidase, a potent generator of highly reactive and damaging free radicals known as reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide. In parallel to, and perhaps as a consequence of, the increased ROS production, the levels of the protective antioxidant, glutathione (GSH), are decreased by as much as 80 to 90 percent in the air sacs of the lung (i.e., alveoli). As a consequence, the expression of a protein involved in immune system regulation, transforming growth factor β (TGFβ), is increased. When activated in the alveoli (particularly during acute inflammatory stresses), TGFβ disrupts the normally tight alveolar epithelial barrier that allows the alveoli to remain air-filled. The net result is a marked increase in the leakage of protein and fluid into the alveolar space and the development of respiratory failure.1 The renin-angiotensin system is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3860447&req=5

f2-arh-31-1-66: Proposed pathophysiological sequence by which alcohol abuse renders the lung susceptible during acute inflammatory stresses such as infection (i.e., sepsis) and trauma. Alcohol abuse activates the renin-angiotensin system1 which, via its active mediator angiotensin II, increases the expression and activity of the enzyme NADPH oxidase, a potent generator of highly reactive and damaging free radicals known as reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide. In parallel to, and perhaps as a consequence of, the increased ROS production, the levels of the protective antioxidant, glutathione (GSH), are decreased by as much as 80 to 90 percent in the air sacs of the lung (i.e., alveoli). As a consequence, the expression of a protein involved in immune system regulation, transforming growth factor β (TGFβ), is increased. When activated in the alveoli (particularly during acute inflammatory stresses), TGFβ disrupts the normally tight alveolar epithelial barrier that allows the alveoli to remain air-filled. The net result is a marked increase in the leakage of protein and fluid into the alveolar space and the development of respiratory failure.1 The renin-angiotensin system is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.

Mentions: As noted previously, alcohol-induced oxidative stress impairs multiple critical cellular functions within the lung. In particular, the critical barrier function within the alveolar epithelium is compromised. Under normal conditions, the alveolar epithelium is a tight barrier that allows the alveoli to remain air filled despite their close proximity to the lung’s small blood vessels (i.e., capillaries), through which the entire cardiac output courses. This dynamic barrier physically restricts the leakage of fluid into the alveolar space but also actively transports sodium and fluid out of the alveolar space in order to maintain this gas exchange unit. In light of the effects of alcohol on alveolar epithelial viability reported above, it is not surprising that chronic alcohol ingestion increases alveolar epithelial protein leakage and decreases the lungs’ ability to remove liquid in the rat model in vivo (Guidot et al. 2000). Again consistent with the gene expression data reported above, recent findings suggest that TGFβ1 mediates many of these effects. Chronic alcohol ingestion, via the sequential actions of angiotensin II and glutathione depletion, markedly increases the expression of TGFβ1 in the rat lung (Bechara et al. 2004, 2005). During acute inflammatory stresses such as sepsis and trauma, TGFβ1 is released and activated in the alveolar space, where it can cause the alveolar epithelial barrier dysfunction described above (Bechara et al. 2004). Therefore, the experimental findings to date implicate the pathophysiological sequence in the alcoholic lung shown in figure 2.


Alcoholic lung disease.

Kershaw CD, Guidot DM - Alcohol Res Health (2008)

Proposed pathophysiological sequence by which alcohol abuse renders the lung susceptible during acute inflammatory stresses such as infection (i.e., sepsis) and trauma. Alcohol abuse activates the renin-angiotensin system1 which, via its active mediator angiotensin II, increases the expression and activity of the enzyme NADPH oxidase, a potent generator of highly reactive and damaging free radicals known as reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide. In parallel to, and perhaps as a consequence of, the increased ROS production, the levels of the protective antioxidant, glutathione (GSH), are decreased by as much as 80 to 90 percent in the air sacs of the lung (i.e., alveoli). As a consequence, the expression of a protein involved in immune system regulation, transforming growth factor β (TGFβ), is increased. When activated in the alveoli (particularly during acute inflammatory stresses), TGFβ disrupts the normally tight alveolar epithelial barrier that allows the alveoli to remain air-filled. The net result is a marked increase in the leakage of protein and fluid into the alveolar space and the development of respiratory failure.1 The renin-angiotensin system is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860447&req=5

f2-arh-31-1-66: Proposed pathophysiological sequence by which alcohol abuse renders the lung susceptible during acute inflammatory stresses such as infection (i.e., sepsis) and trauma. Alcohol abuse activates the renin-angiotensin system1 which, via its active mediator angiotensin II, increases the expression and activity of the enzyme NADPH oxidase, a potent generator of highly reactive and damaging free radicals known as reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide. In parallel to, and perhaps as a consequence of, the increased ROS production, the levels of the protective antioxidant, glutathione (GSH), are decreased by as much as 80 to 90 percent in the air sacs of the lung (i.e., alveoli). As a consequence, the expression of a protein involved in immune system regulation, transforming growth factor β (TGFβ), is increased. When activated in the alveoli (particularly during acute inflammatory stresses), TGFβ disrupts the normally tight alveolar epithelial barrier that allows the alveoli to remain air-filled. The net result is a marked increase in the leakage of protein and fluid into the alveolar space and the development of respiratory failure.1 The renin-angiotensin system is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.
Mentions: As noted previously, alcohol-induced oxidative stress impairs multiple critical cellular functions within the lung. In particular, the critical barrier function within the alveolar epithelium is compromised. Under normal conditions, the alveolar epithelium is a tight barrier that allows the alveoli to remain air filled despite their close proximity to the lung’s small blood vessels (i.e., capillaries), through which the entire cardiac output courses. This dynamic barrier physically restricts the leakage of fluid into the alveolar space but also actively transports sodium and fluid out of the alveolar space in order to maintain this gas exchange unit. In light of the effects of alcohol on alveolar epithelial viability reported above, it is not surprising that chronic alcohol ingestion increases alveolar epithelial protein leakage and decreases the lungs’ ability to remove liquid in the rat model in vivo (Guidot et al. 2000). Again consistent with the gene expression data reported above, recent findings suggest that TGFβ1 mediates many of these effects. Chronic alcohol ingestion, via the sequential actions of angiotensin II and glutathione depletion, markedly increases the expression of TGFβ1 in the rat lung (Bechara et al. 2004, 2005). During acute inflammatory stresses such as sepsis and trauma, TGFβ1 is released and activated in the alveolar space, where it can cause the alveolar epithelial barrier dysfunction described above (Bechara et al. 2004). Therefore, the experimental findings to date implicate the pathophysiological sequence in the alcoholic lung shown in figure 2.

Bottom Line: This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality.However, there have been no systems biological approaches to the study of the alcoholic lung to date.However, the alcoholic lung represents a clear example of environment-host interactions that should be well suited for such applications.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia.

ABSTRACT
In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality. Experimental and clinical studies are shedding light on the basic mechanisms by which alcohol abuse predisposes some people to both acute lung injury and pneumonia. At the same time, novel therapeutic targets could be utilized in treating these uniquely vulnerable people. However, there have been no systems biological approaches to the study of the alcoholic lung to date. This is in part because the association between alcohol abuse and acute lung injury was made relatively recently and remains largely unrecognized, even by lung researchers. In parallel, efforts to study complex diseases such as acute lung injury and pneumonia using a genomics and/or proteomics approach, which involves the study of an organism's genes and/or proteins, still are in their infancy. However, the alcoholic lung represents a clear example of environment-host interactions that should be well suited for such applications.

Show MeSH
Related in: MedlinePlus