Murder mystery solved

CHICAGO --- It was a murder mystery playing out in major cities across the country and perplexing scientists. Thousands of people were dying from strokes and heart attacks within 24 hours of a spike in microscopic pollution -- tiny particles that spew from the exhaust of diesel trucks, buses and coal-burning factories.

But scientists didn't have a smoking gun. They couldn't figure out why the pollution was triggering the deaths. All they had to go on was a vague lead: the particles -- too small to be filtered by the nose or mouth -- caused inflammation of the lungs. But what was the link between particles trapped in the lungs to the strokes and heart attacks"

New research from the gumshoes at Northwestern University’s Feinberg School of Medicine has solved a key piece of the mystery. The study identifies how these tiny pieces of soot -- called particulate matter air pollution -- kill people at risk and tells how they can protect themselves from these pollution-related strokes and heart attacks.

Northwestern researchers have discovered that this microscopic air pollution – smaller than 10 microns or less than one-tenth of the diameter of a human hair -- spurs hyperclotting of the blood. The study found that lungs inflamed by the pollution secrete a substance, interleukin-6, which causes an increased tendency for blood to coagulate or clot. This raises the risk of a fatal heart attack or stroke in people with cardiovascular disease such as coronary artery disease, congestive heart failure or a history of stroke.

Previous epidemiological research has linked the pollution to cardiovascular death and disease, but this is the first study to show how it actually happens in an animal model.

"This is a critical missing piece of the puzzle that has eluded scientists for decades," said Gokhan Mutlu, M.D., lead author of the study and assistant professor of pulmonary and critical care medicine at the Feinberg School, and a physician at Northwestern Memorial Hospital. "Now we know how the inflammation in the lungs caused by air pollutants leads to death from cardiovascular disease."

People at risk can probably help protect themselves by taking low-dose aspirin to keep their blood thin, Mutlu said.

Mutlu collaborated on the study with co-authors Scott Budinger, M.D. associate professor of pulmonary and critical care medicine, and David Green, M.D., professor of hematology and oncology, both at the Feinberg School and physicians at Northwestern Memorial Hospital.

The paper will appear on-line Sept. 20 in the Journal of Clinical Investigation and will be published in the print issue October 1.

In the study, researchers used particles of pollution collected by the United States Environmental Protection Agency, mixed them into a saline solution and injected the pollution cocktail into the lungs of mice. The blood of the mice exposed to the pollution clotted faster than mice not exposed. Researchers observed a 15-fold increase in interleukin-6 24 hours after the mice were exposed to the pollution.

In people, interleukin-6 also raises the levels of a substance called CRP, which is correlated with death from cardiovascular disease.

Particulate matter pollution is highest near expressways or truck routes. It's hard for commuters to escape. People are exposed to the pollution inside a car (even with the windows rolled up), a train or walking outdoors, Mutlu said. The only safe location with lower levels is indoors.

People with previous blockages in the coronary or carotid arteries are at the highest risk. "It's important to get screened to see if you have one of these conditions. If so, when there are high levels of particulate matter, you should try to stay indoors and limit your exposure to the outside air," Budinger said.

Exercising hikes the risk because it floods the lungs with more polluted air. "If you're sitting down, the amount of air you get into your lungs is about five to six liters per minute, but if you're running the amount is 20 to 25 liters," Mutlu noted. "If you’re close to an expressway, you're actually breathing more particulate matter into your lungs."

The doctors also warned that heart attacks and strokes occur at relatively low levels of particulate matter pollution. "We haven't found a safe level yet," Mutlu said. He hopes the study helps encourages the EPA and local regulators to reduce the limits on particulate matter levels.

The American Lung Association State of the Air: 2007 report said the most "ominous trend" in air pollution is the increase in particle pollution, particularly in the eastern United States. Among the metropolitan areas, Los Angeles has the most year-round particle pollution. Chicago ranks 11; New York, 17 and Washington D.C., 20. All received an "F" or failing grade for their pollution , which was in excess of the EPA annual average limit of 15 micrograms per cubic meter.

The risk of dying from a heart attack or ischemic stroke jumps a whopping 30 percent with each additional 10 micrograms of pollution.

While the current Northwestern study looked at the acute effects of this microscopic pollution, Mutlu also has begun to research its long-term exposure on cardiovascular health. He is piping air on the street from Huron and Lake Shore Drive in downtown Chicago into a chamber with mice. Over the next several years, he will examine the effect of breathing this air on the mice's cardiovascular health.

The National Institute of Environmental Health Sciences supported the study.

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