Chronic obstructive pulmonary disease (COPD) is a serious public health problem that disables millions of Americans each year, yet it is one of the most understudied chronic human illness. The American Lung Association states that COPD is the fourth leading cause of death, claiming the lives of 119,524 Americans annually.

Although the incidence of COPD is rising, several major developments within the last few years have sparked new optimism for treating COPD patients. Advances in cellular and molecular immunology have given scientists new ways of looking at lung disease. Research into the human genome may help explain why some people have a higher risk of developing COPD than others. Scientists anticipate that current research will lead to new breakthroughs in the early detection and cure of COPD.

Several excellent resources are available that address current understanding of this disease. The National Heart, Lung, and Blood Institute (NHLBI) recently convened an expert group charged with recommending future directions for COPD research.

The expert panel found “encouraging indications for future COPD research” as they examined enigmas and apparent contradictions in COPD research to date. They identified promising areas of current research, including the diversity of protease functions, mucous hyper-secretion, apoptosis, the role of blood vessels, the possibility of alveolar regeneration, identification of chemical markers, the influence of heredity, developments in imaging technologies, and the potential for new pharmaceuticals. The group’s recommendations were published in the American Journal of Respiratory and Critical Care Medicine, Volume 165, Issue 6, on March 15, 2002. The results can also be found on the NHLBI website at:

 http://www.nhlbi.nih.gov/meetings/workshops/copd_wksp.htm

A National Institutes of Health publication, “Chronic Obstructive Pulmonary Disease (COPD),” provides a detailed look at COPD, including diagrams of the airways and descriptions of disease symptoms, methods of detection, and treatment. Special attention is given to ways in which patients and their families can cope with this illness and to the types of clinical research underway aimed at understanding the causes, improving treatment, and helping patients manage the disease. (Publication No. 95-2020; see http://www.nhlbi.nih.gov/health/public/lung/other/copd/index.htm)

The Medline Plus Health Information website is another source for the latest COPD news, overviews, statistics, anatomy/physiology, clinical trials, treatments/disease management,” and other resources.

http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.html

Currently prescribed medications for COPD include home oxygen therapy, bronchodilators (which help to open narrow passageways), and corticosteroids (which decrease airway inflammation). A number of therapies in clinical trials show much promise. These include muscarinic antagonists/cholinergics (e.g., Spiriva), beta 2 adrenoreceptor agonists (bronchodilators), particularly in combination with other drugs such as corticosteroids (e.g., Advair), and phosphodiesterase inhibitors (e.g., Airflo).

For a list of COPD clinical trials in the United States, visit: http://www.centerwatch.com/patient/studies/cat44.html.

LRRI Contributes to Finding a Cure

Lovelace Respiratory Research Institute (LRRI) is actively involved in many of the areas of research identified above.

LRRI is working with pharmaceutical companies to develop new chemopreventive pharmaceuticals that slow the onset of COPD, reduce the rate of decline in lung function, and possibly reverse existing damage. New drugs are best tested using an animal model that shows the same emphysematous and inflammatory changes in the lung as are seen in humans who smoke cigarettes (the main cause of emphysema). To test new therapies, Dr. Thomas March is using a mouse model of cigarette smoke-induced emphysema. Mice that inhale cigarette smoke and develop emphysema not only show the enlarged alveoli and tissue destruction seen in human emphysema, but the same chronic inflammation and deposits of tar. Drugs that are beneficial in this animal model are more likely to be effective in humans.

Doctors often prescribe corticosteroids for patients with COPD. However, a December 2000 NHLBI study concluded that inhaled corticosteroids do not slow the progression of COPD. (For more information, visit http://www.nih.gov/news/pr/dec2000/nhlbi-27.htm). Although they may not improve actual lung capacity, corticosteroids are potent anti-inflammatory agents that reduce airway inflammation, decrease mucus secretion, and reduce airway hyper-responsiveness. All of these factors contribute to the onset and progression of COPD, and suggest that use of corticosteroids might be beneficial. Dr. Floyd Frost and colleagues at the LRRI Center for Pharmacoeconomic and Outcomes Research have been conducting epidemiological studies of COPD patients to learn how different COPD treatments impact health outcomes. Their findings, presented recently at the annual meeting of the American College of Chest Physicians, indicate that inhaled corticosteroid use is associated with longer survival. Dr. Frost's team is also studying patients with a history of acute respiratory infections and antibiotic use to determine if COPD can be identified and treated in its earliest stages, before symptoms become severe.

A common feature of COPD, particularly chronic bronchitis, is the constant production of excess mucus. As a result, airflow may be restricted and an irritating cough can develop. The excess mucus also provides an ideal breeding place for infections. Controlling excess mucus production, therefore, may be one strategy for treating chronic bronchitis. Cigarette smoking and other environmental toxins can change the normal proportion of cell types in airways and lead to greater production of mucus-producing cells. At LRRI, Dr. Yohannes Tesfaigzi is exploring the use of new drug therapies, such as topically applied gamma-interferon, to help to reverse these changes and bring cell populations back to normal proportions.

The genetics of COPD are entirely unknown. Differences in genetics probably explain why only 10-20% of the people at risk for the disease will develop emphysema. Identification of “COPD genes” might help to identify susceptible individuals, and more importantly, help guide the development of more effective treatments. Dr. Tesfaigzi is using molecular biology techniques to find alternative forms of suspect genes known as genetic polymorphisms. Hundreds of smokers with and without emphysema are being screened for these gene variants. Volunteers are given a physical and have blood taken for subsequent genetic analysis. If COPD genes are found, the results might suggest gene therapies to turn off these aberrant genes or drugs that might attack the gene products directly.

These are some of the research areas that hold promise.  They cover the basic disease process involved in COPD, new ways to detect COPD sooner, better handling of clinical information about COPD patients, and better treatment options for the future.

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Last modified: 07/19/04