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Ciptapangan Visitor
Even Without a Vaccine, Existing Drugs Show Promise
posted by admin on 04/04/06

No one knows whether an avian flu pandemic will ever strike, or if a viable vaccine will be found before it does. 

But many of the life-threatening symptoms of the flu resemble other conditions that are occurring in thousands of patients now, and the drugs to treat these conditions could be used to treat the bird flu, researchers say.
 
One of those conditions is acute respiratory distress syndrome, or ARDS, a lung condition involving inflammation and fluid buildup that often follows viral pneumonia and septic infections. Drugs to treat such conditions may be useful for treating bird flu, even if vaccines and antivirals aren't available.
 
Because the avian flu virus acts much the same way as ARDS, researchers are now hard at work studying drugs currently used to treat ARDS that could have the potential to fight bird flu too. "We have a lot to offer people if the flu should strike." says Michael A. Matthay, a researcher at the University of California-San Francisco. 

Some of the drugs are exotic and experimental, used so far only on mice. Other pills are household names, such as Merck & Co.'s cholesterol drug Zocor and the generically available asthma drug albuterol. Some are in-between, like Eli Lilly & Co.'s Xigris for septic infections, which is used in emergency settings at thousands of dollars a dose. 

What these medicines have in common is the ability to fight the constellation of lethal symptoms of ARDS, which some researchers call "vascular leak" because the walls of blood vessels supplying the lungs grow inflamed and porous, causing fluid to seep into the lungs. About 75,000 Americans die annually from ARDS and related conditions, according to critical-care physicians. Researchers at leading institutions like the University of Chicago, the University of Michigan and UCSF are working on ways to treat vascular leak, partly by enhancing the walls of capillaries that supply the lungs. 

"If vaccinations do not prevent it, therapy for bird flu is no different than for the inflammatory process of ARDS," says Augustine Choi, chief of pulmonary and critical-care medicine at the University of Pittsburgh Medical Center. 

The avian flu virus has killed more than 100 humans since its detection in Hong Kong in 1997. Recent research suggests that because it mostly infects cells deep in the lung, it might be difficult for the virus to spread from person to person. However, some doctors say the deep-lung viral attack may make people cough more heavily and thus make the illness highly transmissible. The government hopes it can ward off a flu epidemic with its stockpile of antiviral drugs and with vaccines in development, but that's far from a certainty. The Asian strain of H5N1, which is known to mutate rapidly, has shown resistance in human cases to antivirals. A recent test of a vaccine in development by the U.S. government and France's Sanofi-Aventis SA had only tepid success. 

Doctors are optimistic that statins, the class of cholesterol-lowering drugs that includes Zocor and Pfizer Inc.'s Lipitor, could play a role. That's because statins also fight the inflammation that causes leaky vessels. Although these drugs aren't currently prescribed for respiratory illnesses, "statins could be part of a world-wide effort to reduce morbidity and mortality from avian flu," says Joe G.N. Garcia, chief of medicine at the University of Chicago and a leading lung-disease researcher. 

At the University of Chicago, pulmonologist and critical-care doctor Jeffrey R. Jacobson and colleagues have produced ARDS in mice, then hooked the mice up to miniature ventilators as humans with avian flu might be. The mice were then tested with treatments like Zocor, generically called simvastatin. The researchers found that simvastatin relieved vascular leakage and enhanced the artery-wall barrier keeping fluids in -- and that these findings "have broad clinical implications." 

"We've clearly demonstrated that these drugs affect blood-vessel function," Dr. Jacobson says. 

There's also evidence that statins can help in humans in respiratory distress. Doctors at Ben Gurion University in Israel found that, of patients admitted to the hospital with acute bacterial infections, use of statins made a big difference. The 2004 study of 361 patients found that 19% of the no-statin patients needed intensive care when their infections progressed to severe sepsis, versus 2.4% of those who had taken statin drugs. 

While the study involved using statins as a cholesterol drug, researchers believe giving them early in treatment could produce similar beneficial effects for respiratory illnesses. Using Zocor "would be the lowest-hanging fruit" of possible drugs for bird flu because it's relatively inexpensive, and already widely available, Dr. Garcia says. 

It also could get patients off ventilators faster. That's important because the ventilator itself can cause injury to the lungs. And if an epidemic were to strike, ventilators could become a scarce commodity. 

Dr. Garcia and colleagues have found that experimental drugs that mimic a naturally occurring compound in the body, sphingosine 1-phosphate, produced "significant decreases" in vascular leakage in animal tests. Scientists also have found that Lilly's Xigris, already on the market, appears to build up capillary walls that hold in fluid. UCSF's Dr. Matthay and colleagues are investigating the use of the asthma drug albuterol in ARDS patients. It acts, he says, by "removing fluid from the air spaces of the lungs, and it may also work by decreasing inflammation of the lungs." 

And if bird flu never strikes, much of this research will nevertheless be vital: The University of Chicago's Dr. Jacobson says that, at any given time, more than one-fourth of patients in the medical intensive-care unit are suffering from acute respiratory distress and related conditions. 

Tara Parker-Pope returns next week. Email questions to healthjournal@wsj.com, and read her responses in this section. 

Write to Thomas M. Burton at tom.burton@wsj.com

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