Medical Edge Newspaper Column

Emphysema Research: Proceeding Along Multiple Lines

Jan. 7, 2007
Dear Mayo Clinic:
Is research producing any results for the treatment or cure of emphysema -- for example, by regenerating alveoli? I have about 25 percent lung function due to damaged alveoli. -- Henderson, Nev.

Answer:
Funding for research in emphysema has increased dramatically in recent years, and results have been encouraging. They include the example you suggest, which derives from the 1997 finding that retinoic acid, a derivative of vitamin A, reverses emphysema in the lungs of laboratory rats by regenerating the lungs' tiny air sacs (alveoli).

That study prompted further inquiry, most notably the Feasibility of Retinoic Acid Treatment in Emphysema (FORTE) study sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The particular agent used in the study, called "all-trans retinoic acid," did not produce a measurable benefit in emphysema patients, but vitamin A derivatives nevertheless have shown promise.

Emphysema is a chronic condition in which the fragile walls of the alveoli are damaged by inflammation and other factors. They lose their oxygen-absorption ability and also their elasticity. Air becomes trapped in the alveoli, overstretching the lungs and compromising breathing. As emphysema progresses, shortness of breath and reduced exercise capacity become more severe.

Because the major cause of emphysema is smoking, the most effective prevention and treatment is to not smoke or quit smoking. Until recently, the best available drug for smoking cessation was bupropion (brand names are Wellbutrin and Zyban) in combination with nicotine replacement and counseling. Newer research has produced an even more effective medication -- varenicline (brand name Chantix) -- which was recently approved by the U.S. Food and Drug Administration. This medication prevents the craving for nicotine by binding to the brain's nicotine receptors, tricking them into "thinking" they've received nicotine.

An important area of emphysema research involves the surgical procedure called lung volume reduction surgery (LVRS), though a major national study concluded that it only helps certain subgroups of patients. LVRS is invasive, and the benefit rather modest, so demand for it in the last few years was lower than expected.

A less invasive alternative, bronchoscopic lung volume reduction, is now being pursued. It involves placing one-way valves in the bronchial tubes to help reduce areas of overinflation within the lungs most severely affected by emphysema (as opposed to removing damaged tissue from the lungs by means of LVRS). Several companies are working on such devices, which are in various stages of development.

New kinds of drugs are also being developed. While some emphysema drugs aim to prevent damage to lung tissue by blocking inflammation, a new approach is to turn off apoptosis -- programmed cell death -- to prevent the disease's progression. Inhibitors of the enzyme histone deacetylase, for example, are among the most promising agents.

There are many exciting developments in research that may translate into more effective treatments in the future. Meanwhile, it is important for patients to be sure that they are benefiting from well-established and effective therapies. These are specified in the guidelines for treatment of Chronic Obstructive Pulmonary Disease (COPD) -- which includes emphysema -- published by the American Thoracic Society, the NHLBI, and the World Health Organization. Unfortunately, many emphysema patients are not being treated according to the COPD guidelines.

For example, bronchodilators, which help relieve symptoms by opening constricted airways, are currently the mainstay of therapy. Long-acting bronchodilators, taken once or twice a day, provide base protection, while short-acting bronchodilators are quick relief medications to be taken only as needed. Yet many COPD patients who should have prescriptions for long-acting bronchodilators do not have them. Meanwhile, inhaled corticosteroids, by themselves, are overused. While indicated for patients with moderate to severe obstruction and frequent exacerbations, they are often given to other patients, with little positive effect.

Influenza immunization is very effective but underutilized, as are exercise rehabilitation programs, which improve quality of life scores and exercise tolerance, and may reduce hospitalization rates.

Patients should discuss the guidelines with their doctors to be sure they are receiving the best currently available care before exploring experimental therapy.

-- Paul D. Scanlon, M.D., Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minn.