Between 3 and 7 million Americans are currently diagnosed with chronic obstructive pulmonary disease (COPD), and the true prevalence is probably greater than 16 million (1). Many of these individuals suffer years of progressive discomfort and disability. With the number of deaths per year attributed to this disease at approximately 100,000 and increasing, COPD is now the fourth leading cause of death in this country (2) and is expected to be third by the year 2020. Cigarette smoking is firmly established as the major cause of COPD, but approximately one-quarter of Americans continue to smoke, despite aggressive smoking prevention and cessation efforts. Better means are clearly needed for the prevention and treatment of COPD, and more scientific research is needed to enable improvements in its clinical management. Unfortunately, research progress in this field has been slow. Most basic scientific research over the past 35 years has focused on the pathogenetic roles of cigarette smoke, inflammation, and protease/antiprotease balance, based on the association of COPD with cigarette smoking and the early discovery that a subgroup of patients with emphysema is genetically deficient in an inhibitor of a neutrophil protease (3). Although the cigarette–inflammation–protease theory captures key features of COPD epidemiology and pathology, this approach has not yet led to a reduction in COPD prevalence or morbidity, to the development of any therapy proven to modify the disease process itself, or to an adequate understanding of how risk factors other than cigarette smoking may contribute to COPD pathogenesis.

However, there are encouraging indications for future COPD research. Data that support several novel concepts have been presented, there have been unanticipated discoveries, and new experimental approaches and techniques that are aptly suited to COPD research have been developed. Furthermore, elucidation of cellular pathways that are critically involved in COPD pathogenesis may lead rapidly to clinical trials of potential therapeutics, given the improving capabilities of the pharmaceutical industry for development of mechanism-specific drugs.