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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.

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Related in: MedlinePlus

Schematic illustration of the mechanisms by which alcohol abuse increases the risk of pneumonia. In addition to altering the normal microbes from the upper part of the throat (i.e., oropharyngeal flora), alcohol abuse impairs both physical barriers to bacterial entry into the lower airways (by diminishing cough and gag reflexes as well as mucus-facilitated [i.e., mucociliary] clearance from the large airways in the chest) and innate immune barriers to airway pathogens. For example, alcohol abuse impairs pathogen ingestion (i.e., phagocytosis) by white blood cells in the air sacs of the lungs (i.e., alveolar macrophages) and other infection-fighting white blood cells (i.e., neutrophils).NOTE: Aspiration: the entry of secretions or foreign material into the trachea and lungs. Chemokines: small proteins involved in immune function. Chemotaxis: directed movement.
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f1-arh-31-1-66: Schematic illustration of the mechanisms by which alcohol abuse increases the risk of pneumonia. In addition to altering the normal microbes from the upper part of the throat (i.e., oropharyngeal flora), alcohol abuse impairs both physical barriers to bacterial entry into the lower airways (by diminishing cough and gag reflexes as well as mucus-facilitated [i.e., mucociliary] clearance from the large airways in the chest) and innate immune barriers to airway pathogens. For example, alcohol abuse impairs pathogen ingestion (i.e., phagocytosis) by white blood cells in the air sacs of the lungs (i.e., alveolar macrophages) and other infection-fighting white blood cells (i.e., neutrophils).NOTE: Aspiration: the entry of secretions or foreign material into the trachea and lungs. Chemokines: small proteins involved in immune function. Chemotaxis: directed movement.

Mentions: Perhaps the most prominent effects on host defense involve the macrophages present in the air sacs, or alveoli, of the lungs (i.e., alveolar macrophages), the first cellular line of defense against pathogens within the lower airways. In experimental models, chronic alcohol ingestion suppresses the responses of small proteins involved in immune function (i.e., chemokines) as well as the pathogen-clearing and immune responses of alveolar macrophages (Arbabi et al. 1999; Boe et al. 2003; D’Souza et al. 1995; Standiford and Danforth 1997; Zhang et al. 1999, 2002a,b; Mason et al. 2000) and even increases experimental tuberculosis in mice (Mason et al. 2004). Such controlled laboratory studies support the evolving recognition that alcohol abuse has specific effects on innate immune function within the lower airways and that the increased risk of pneumonia in alcoholics cannot be ascribed solely to factors such as malnutrition, aspiration, or poor oral hygiene. Alcohol-induced defects in alveolar macrophage function and other components of the lung’s innate immune defenses suggest that alcoholics cannot mount an appropriate response to infections, as evidenced by decreased levels of important molecules in the immune system (i.e., interleukins) at the onset of pneumonia and septic shock, a condition that occurs when infection leads to low blood pressure in alcoholics (von Dossow et al. 2004). The combination of impaired innate and adaptive immune responses within the airways is exacerbated by decreased white blood cells (i.e., lymphocytes) within the body’s immune system tissues (i.e., lymphoid tissue) in alcoholics, further stressing an already suboptimal response to infection (Gamble et al. 2006; Happel and Nelson 2005; Nelson and Kolls 2002). Overall, alcohol abuse alters the host immune defenses from the mouth to the alveolar space and increases the risk for bacterial pneumonia as well as tuberculosis. Some of the major mechanisms by which alcohol abuse renders individuals susceptible to pneumonia are illustrated in figure 1.


Alcoholic lung disease.

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

Schematic illustration of the mechanisms by which alcohol abuse increases the risk of pneumonia. In addition to altering the normal microbes from the upper part of the throat (i.e., oropharyngeal flora), alcohol abuse impairs both physical barriers to bacterial entry into the lower airways (by diminishing cough and gag reflexes as well as mucus-facilitated [i.e., mucociliary] clearance from the large airways in the chest) and innate immune barriers to airway pathogens. For example, alcohol abuse impairs pathogen ingestion (i.e., phagocytosis) by white blood cells in the air sacs of the lungs (i.e., alveolar macrophages) and other infection-fighting white blood cells (i.e., neutrophils).NOTE: Aspiration: the entry of secretions or foreign material into the trachea and lungs. Chemokines: small proteins involved in immune function. Chemotaxis: directed movement.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f1-arh-31-1-66: Schematic illustration of the mechanisms by which alcohol abuse increases the risk of pneumonia. In addition to altering the normal microbes from the upper part of the throat (i.e., oropharyngeal flora), alcohol abuse impairs both physical barriers to bacterial entry into the lower airways (by diminishing cough and gag reflexes as well as mucus-facilitated [i.e., mucociliary] clearance from the large airways in the chest) and innate immune barriers to airway pathogens. For example, alcohol abuse impairs pathogen ingestion (i.e., phagocytosis) by white blood cells in the air sacs of the lungs (i.e., alveolar macrophages) and other infection-fighting white blood cells (i.e., neutrophils).NOTE: Aspiration: the entry of secretions or foreign material into the trachea and lungs. Chemokines: small proteins involved in immune function. Chemotaxis: directed movement.
Mentions: Perhaps the most prominent effects on host defense involve the macrophages present in the air sacs, or alveoli, of the lungs (i.e., alveolar macrophages), the first cellular line of defense against pathogens within the lower airways. In experimental models, chronic alcohol ingestion suppresses the responses of small proteins involved in immune function (i.e., chemokines) as well as the pathogen-clearing and immune responses of alveolar macrophages (Arbabi et al. 1999; Boe et al. 2003; D’Souza et al. 1995; Standiford and Danforth 1997; Zhang et al. 1999, 2002a,b; Mason et al. 2000) and even increases experimental tuberculosis in mice (Mason et al. 2004). Such controlled laboratory studies support the evolving recognition that alcohol abuse has specific effects on innate immune function within the lower airways and that the increased risk of pneumonia in alcoholics cannot be ascribed solely to factors such as malnutrition, aspiration, or poor oral hygiene. Alcohol-induced defects in alveolar macrophage function and other components of the lung’s innate immune defenses suggest that alcoholics cannot mount an appropriate response to infections, as evidenced by decreased levels of important molecules in the immune system (i.e., interleukins) at the onset of pneumonia and septic shock, a condition that occurs when infection leads to low blood pressure in alcoholics (von Dossow et al. 2004). The combination of impaired innate and adaptive immune responses within the airways is exacerbated by decreased white blood cells (i.e., lymphocytes) within the body’s immune system tissues (i.e., lymphoid tissue) in alcoholics, further stressing an already suboptimal response to infection (Gamble et al. 2006; Happel and Nelson 2005; Nelson and Kolls 2002). Overall, alcohol abuse alters the host immune defenses from the mouth to the alveolar space and increases the risk for bacterial pneumonia as well as tuberculosis. Some of the major mechanisms by which alcohol abuse renders individuals susceptible to pneumonia are illustrated in figure 1.

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