Newswise — Physicians have long known that too little oxygen (hypoxia) causes headaches, nausea, and eventually death. But too much oxygen (hyperoxia) can kill to, as evidenced in a new study by Northeastern University Professor Michail Sitkovsky, Ph.D and colleagues which has revealed that oxygen therapy aimed at helping those with acute lung inflammation breathe, instead worsens their illness. The research, performed on gene-altered mice, indicates that excess oxygen appears to thwart a natural process that limits lung tissue damage. Researchers overcame this deleterious side effect, however, by adding an inhaled anti-inflammatory drug to the oxygen therapy.
Sitkovsky, senior author of the paper published this week in the journal PLoS Biology, believes the findings could have important clinical applications. For example, acute respiratory distress syndrome (ARDS), a life-threatening inflammation of the lung following injury or infection, causes more than 50,000 deaths in the United States each year. ARDS is characterized by fluid filling the lung cells, which greatly impedes breathing.
"In cases of ARDS," Sitkovsky says, "the current practice of routinely given oxygen therapy may actually promote lung inflammation and fuel the disease process. Based on our findings, we suggest that standard protocols for ventilation and oxygenation of human patients with acute lung inflammation due to infection or other causes, such as exacerbated asthma or surgical trauma, be re-evaluated."
The research, conducted at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, was based on insights published in 2001 by Dr. Sitkovsky and colleagues into the role played by extracellular adenosine - a common cellular molecule in regulating inflammation. Now they show that it is the inflammation-associated drop in oxygen level in damaged tissues that is triggering the release of adenosine from surrounding cells. The binding of adenosine to its cellular receptor acts a a tissue-protecting stop signal, slowing the flood of damaging inflammatory molecules, the scientists found.
From these findings, they reasoned that oxygen therapy given to patients with acute lung inflammation might prevent oxygen levels from dropping enough to trigger the inflammation stop signal. To explore this possibility in an animal model, Dr. Sitkovsky and his colleagues induced lung inflammation in three groups of mice. The first group of 15 mice did not receive any supplemental oxygen. While they sustained moderate lung damage, only two died. Another group of 15 mice with acute lung inflammation were treated with either 100 percent or 60 percent oxygen for 48 hours-mimicking supplemental oxygen therapy as typically applied in a hospital. These mice suffered very extensive lung damage, and 11 of 15 mice treated with 100% oxygen died. Finally, the scientists treated another 15 mice with acute lung inflammation with a combination of oxygen and an adenosine-like drug in order to compensate for the oxygen-induced loss of adenosine. Only two mice in this group died and exacerbation of lung inflammation by oxygen was prevented. The investigators conclude that oxygen therapy without the addition of an adenosine substitute exacerbates pre-existing lung inflammation. Dr. Sitkovsky is continuing his research at the New England Inflammation and Tissue Protection Institute, a Consortium at Northeastern University in Boston.
Northeastern University, located in the heart of Boston, Massachusetts, is a world leader in practice-oriented education and recognized for its expert faculty and first-rate academic and research facilities. Northeastern integrates challenging liberal arts and professional studies with the nation's largest cooperative education program. Through co-op, Northeastern undergraduates alternate semesters of full-time study with semesters of paid work in fields relevant to their professional interests and major, giving them nearly two years of professional experience upon graduation. The majority of Northeastern graduates receive a job offer from a co-op employer. Cited for excellence three years running by U.S. News & World Report, Northeastern has quickly moved up into the top tier rankings-an impressive 30 spots in three years. In addition, Northeastern was named a top college in the northeast by the Princeton Review 2003/04. For more information, please visit http://www.northeastern.edu.
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PLoS May 3rd (3-May-2005)