Physicians say that smoking is by far the biggest cause of emphysema, but why doesn't every smoker get the disease? If you asked Michael Holtzman, M.D., that question, he might answer that for most cases of emphysema you need a mix of genes, viruses and cigarettes.

Emphysema and the associated condition of chronic bronchitis are both disorders that contribute to chronic obstructive pulmonary disease (COPD), which is the fourth leading cause of death in the United States.

Research by Holtzman and his colleagues at Washington University School of Medicine in St. Louis suggests that someone destined to suffer from COPD may start with a susceptible genetic makeup and then experience a severe viral lung infection in early childhood.

The infection could "reprogram" the cells of the lung's air passages and sacs, and the reprogrammed cells could react badly if the same person took up cigarette smoking, leading to COPD some time down the road.

"Cigarette smoking has created a very large population of COPD patients worldwide," he says. "At present, we can treat them with steroids to reduce inflammation, antibiotics to suppress infections, and oxygen to help their breathlessness, but the disease will still progress until it's fatal. We need to find treatments that stop the disease progression and to do that we need a much better understanding of how COPD develops."

Now Holtzman and his colleagues at the School of Medicine have obtained funds from National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) totaling $14.9 million to establish a Specialized Center for Clinically Oriented Research (SCCOR), an ambitious type of grant program meant to foster research that can quickly apply basic science findings to clinical problems.

Holtzman's SCCOR program will take a comprehensive look at the molecular changes that occur as lungs become crippled by COPD a disease that affects at least 16 million people in the United States today.

Lungs have a tree-like structure of intricately branching airways ending in tiny sacs or alveoli, which exchange gases between the blood and the air. In chronic bronchitis, airways overproduce mucus and become inflamed, obstructing airflow. In emphysema, alveoli are destroyed so they can no longer take up oxygen from the air. COPD patients can have both problems at once, and Holtzman and his colleagues are studying both issues.

COPD Facts

• COPD is the 4th leading cause of death in the US and the 2nd leading cause of disability
• COPD kills more than 120,000 Americans each year. That's one death every 4 minutes
• More than 12 million people are diagnosed with COPD
• An additional 12 million likely have COPD and don't even know it

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Researchers will use newly developed imaging techniques, such as helium MRI, to look at the tissue of lungs removed from COPD patients undergoing lung transplants and home in on the tiny lung structures that are injured. "Then, if we find that a particular gene is overactive at a site where the disease is particularly severe, we'll analyze the normal and abnormal function of that specific gene," Holtzman says.

Holtzman notes that so far no other researchers have done this because it takes a combination of new imaging techniques, advanced gene analysis technologies and a highly active lung transplant program all of which are on hand at the School of Medicine.