By Valerie Gregg • Illustration by Christopher Hickey
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The genteel professor was admitted to the ER wearing the academic uniform of a bygone era—bow tie, suspenders, and suit coat. He had suffered a heart attack, and by the second day of his hospitalization, it became apparent that something else was seriously wrong. The gentleman’s trembling hands and agitated affect worried the physicians caring for him. But until his wife acknowledged her prominent husband’s drinking problem, they didn’t know for sure that the patient was suffering from alcohol withdrawal.
That omission could have cost the patient his life. “It’s important for us to know if someone has a chronic drinking problem when they come to the hospital for any reason,” says David Guidot, director of the Emory Alcohol and Lung Biology Center at the Atlanta Veterans Affairs Medical Center (VAMC). “When alcoholics are in septic shock or have suffered severe trauma, they are far more likely to develop acute respiratory distress syndrome (ARDS).”
About half of ARDS patients die, their condition usually deteriorating until they end up on ventilators in intensive care. ARDS is deadly for anyone. But clinical studies at Emory and elsewhere have shown that, overall, the risk of developing and therefore dying of this severe form of lung injury is four times higher for alcoholics than non-alcoholics.
“And these alcoholics die young,” says Guidot. “The average age of death from ARDS related to underlying alcohol abuse is about 30, even among otherwise healthy people. By contrast, the average age of death from alcohol-related cirrhosis is 60 to 65.”
Alcoholism is well known for its role in cirrhosis of the liver, pancreatitis, gout, brain damage, and other ailments that usually develop after many years of alcohol abuse. The little known truth is that more alcoholics may die from lung injury than liver damage, Guidot notes. The reason: too much alcohol depletes the lungs of the vital antioxidant glutathione.
Exactly how much does moderate daily drinking deplete glutathione? Does sporadic binge drinking affect glutathione levels? How exactly should alcoholism be defined?
All of these questions require further study. In the meantime, Guidot knows that much more should be done to treat the medical complications of alcoholism, especially in emergency situations. That is certain to change, as researchers at Emory and elsewhere work to understand the immediate and long-term effects of alcoholism.
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Humanity’s dependence on alcohol didn’t develop overnight. Anthropologists believe people enjoyed alcohol during the Stone Age. it’s going to take a lot of work to learn more fully how a legal substance as widely abused as alcohol inflicts its damage. | |
Wine, beer, hard cider, whiskey, vodka, gin, tequila, rum—it doesn’t matter how the ethanol molecule enters the body. The process of getting drunk is the same. About 20% of the drink swallowed enters the bloodstream from the small intestine. The amount entering the small intestine is controlled by the pyloric valve, which closes when the stomach is full of food. That’s why “drinking your dinner” is a faster way to feel alcohol’s effects.
The immediate process of getting drunk is well documented. Ethanol impacts the brain severely, impeding coordination and judgment. With heavy drinking, the brain stem is affected, producing an effect similar to general anesthesia. A bout of heavy drinking can leave the brain dehydrated, like an old dishrag—hence the dread hangover headache.
Guidot studies what happens when getting drunk becomes a habit. Being a pulmonologist, he concentrates on the long-term health of drinkers’ lungs.
“The lungs are especially vulnerable because chronic drinking depletes them of glutathione, and the alveoli and small airways are very dependent on it,” he says. “Normally, they have 1,000 times more glutathione than other parts of the body. Chronic alcoholics have extremely low levels of glutathione in the lungs.” The alcohol itself doesn’t cause these changes. “It causes oxidative stress, which depletes glutathione in the lung.”
In 1996, results of a landmark study published in JAMA from University of Colorado scientists established a relationship between chronic alcohol abuse and ARDS. Marc Moss, the lead author on the study, joined the Emory medical faculty just before the study was published. Together, Moss, Guidot, and Lou Ann Brown in pediatrics began a collaboration that resulted in the formation of the Emory Alcohol and Lung Biology Center. To study the mechanisms underlying this newly recognized association between alcohol abuse and ARDS, they fed alcohol to rats and discovered that the glutathione levels in their lungs plummeted within just four to six weeks.“Nobody knew drinking had any effect on the lungs,” says Guidot, who has led numerous related studies at Emory for more than a decade.
Since 2003, the Emory Alcohol and Lung Biology Center has received $1.8 million annually from the NIH to investigate alcoholism’s relationship to lung disease. In all, 25 Emory faculty in fields such as neonatology, physiology, and pulmonary and critical care medicine are engaged in related research at Grady Hospital, on the Emory campus, and at the VAMC. Center researchers are competing for an additional five years of NIH funding for the center.
“Emory is the hot spot for the alcohol and lung disease connection,” Guidot says. “It’s an important public health issue, and we put it on the map.”
Guidot and his colleagues hope to lessen the risk of ARDS for alcoholics suffering from trauma. Goals include finding better ways to identify alcoholics when they arrive in emergency departments and developing drugs to increase glutathione levels in patients before they develop ARDS. Researchers also are studying how alcohol abuse intersects with asthma, pneumonia, HIV, and lung transplantation.
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The little known truth is that more alcoholics may die from lung injury than liver damage. The reason: too much alcohol depletes the lungs of the vital antioxidant glutathione. | |
The dangers of alcohol abuse can be as big as a 20-car interstate pileup or as small as a molecular doorway. When drinking heavily becomes a habit, it takes a lot longer than a day to recover physically.
In a clinical study involving the VAMC alcohol inpatient detoxification program, Guidot’s team evaluated otherwise healthy drinkers to examine the effects of alcohol on their lungs before trauma or illness occurred. Glutathione levels in the lungs of these adults were decreased by 80% to 90% compared with healthy nonalcoholics, closely mimicking results from Guidot’s rat studies. Researchers chose young people with normal nutrition (relatively functional alcoholics), waited two to three days after their last drink, made sure they were medically stable, and then measured the glutathione levels in their lungs. After the subjects had gone a week without alcohol, researchers again measured their glutathione levels, which remained very low. Exactly how long it takes the lungs of a chronic drinker to normalize after quitting remains unknown.
In another study, Guidot and colleagues performed a weeklong prospective multicenter study involving hospitals in Atlanta, Denver, and Seattle. The patients studied had been admitted with septic shock, critical blood pressure problems, or other life-threatening conditions. Researchers interviewed patients and their families using standardized questionnaires to identify which patients were alcoholics.
“We followed the alcoholic patients to see how many developed ARDS, and it turned out that the relative risk of ARDS for those with alcohol abuse was closer to 4 to 1 than the 2 to 1 risk that was identified in the original 1996 study,” says Guidot. “The results were dramatic.”
Based on his own recent studies and confirmatory results from other investigators, Guidot estimates that tens of thousands of people in the United States die prematurely every year because of lung injury related to alcohol abuse. The public health ramifications are enormous and have gone largely unrecognized because drinking, like smoking, is a legal choice for people. Studies like Guidot’s make a good case for devoting more federal research dollars to alcohol-related illness. “The people in our studies wouldn’t have developed ARDS in the first place if they were not problem drinkers,” he says.
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Tens of thousands of people in the United States die prematurely every year because of lung injury related to alcohol abuse. The public health ramifications are enormous. | |
Interestingly, Guidot’s animal studies show that alcoholic rats fed with dietary glutathione supplements no longer are susceptible to changes in their lungs, even with continued ingestion of alcohol. The implications of these findings could be enormous if they translate to humans. In particular, glutathione and other nutritional supplements may prove effective in preventing ARDS or other serious alcohol-related problems. However, once acute illnesses from trauma or septic shock come into play, glutathione supplements may not work.
Guidot’s rat studies also have shown that alcoholism affects the body’s absorption of zinc and thiamin as well as glutathione.
“We’re making a good case for providing people in detox with vitamins,” he says. “There’s a very specific protein in the lining of the intestines that helps cells absorb zinc. It’s like a doorway that zinc goes through. Chronic alcohol ingestion suppresses expression of that protein. If that proves to be the case in humans, even if you try to have a good diet, some of the consequences on immune function could be dire.”
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“For alcoholics, the only available treatment is to tell them to stop drinking. We’ve done nothing to minimize the medical complications. ”—VAMC researcher David Guidot |
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A long and mysterious history
Humanity’s dependence on alcohol didn’t develop overnight. Anthropologists believe people enjoyed alcohol during the Stone Age. Even so, knowledge about how to drink alcohol safely is still relatively nonspecific. The National Institute of Alcohol Abuse and Alcoholism states that two drinks a day for men and one for women are safe minus any complicating factors. But assessing an individual’s response to chronic drinking is fuzzy at best.
“It’s very difficult to know based on grams of alcohol how much is too much,” says Guidot. “We know from experience that if someone is getting into car accidents while drunk, having DUIs, going into detox—they’re at a higher risk of developing medical problems.”
To complicate the scenario, people metabolize alcohol at different rates, and many people cannot metabolize alcohol at all. For example, some Asians have enzyme insufficiencies, making them less able to digest alcohol. Smaller women generally are more vulnerable to the effects of alcohol than men.
“That’s an important distinction that our research addresses,” says Guidot. “A person doesn’t have to be drunk at the time of an auto accident to develop ARDS. The effects on the lung from chronic drinking are not from the alcohol molecule itself but rather from the metabolic consequences.”
Much work remains to learn more fully how a legal substance as widely abused as alcohol inflicts its damage. For example: Results of a study using a rat model of lung transplants, published recently in the American Journal of Respiratory and Critical Care Medicine, show that chronic alcohol consumption by the donor promotes scarring and airway injury after transplantation. Guidot’s findings prompted doctors at Emory to begin a clinical study of the post-transplant effects of heavy alcohol use among human lung donors.
“We need to figure out what doctors can do to restore recovering alcoholics to health,” says Guidot. “We don’t wait for people to lose weight and exercise to treat their high blood pressure or their diabetes. For alcoholics, the only available treatment is to tell them to stop drinking. We’ve done nothing to minimize the medical complications. We hope work like ours will help change the situation.”
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© 2008. Emory University, All rights reserved.