High-dose inhaled corticosteroid use for COPD could cut risk of lung cancer

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David H. Au, M.D., M.S., of the Veterans Administration Puget Sound Health Care System in Seattle, along with five associates found that among 10,474 patients with COPD, 517 were considered regular users of ICS.

Among users of more than 1,200 micrograms of ICS per day, the relative risk for lung cancer was lowered to 0.39. For users of less than 1,200 micrograms per day, the relative risk was 1.13. (A relative risk of 1 means there is no difference in risk between two groups.)

Over the next four years, the researchers found that among a total of 9,957 nonusers of ICS, 402 developed lung cancer. For 298 users of ICS at a level below 1,200 micrograms per day, 16 developed lung cancer. Among 219 patients who used over 1,200 micrograms per day, five developed lung cancer.

"Lung cancer is the most common cause of cancer-related death in the United States and accounts for more deaths each year than breast, prostate and colon-rectal cancer combined," said Dr. Au. "Studies such as the Lung Health Study have demonstrated that the most common cause of death among subjects with COPD is lung cancer."

In 2004, more than 11 million U.S. adults were estimated to suffer from COPD, which results from chronic bronchitis and emphysema, two inflammatory lung diseases that frequently co-exist and interfere with normal breathing. Smoking is the primary cause of COPD.

"Tobacco smoke is a well-recognized stimulant of systemic and local inflammation and the role of inflammation in the causal pathway for both lung cancer and COPD has been suggested," said Dr. Au.

The researchers noted that ICS have been shown in prospective studies to suppress systemic markers of inflammation such as C-reactive protein and to reduce airway inflammation.

They hypothesized that higher doses of ICS among the male veterans reduced such factors as local airway inflammation, cell turnover, and the propagation of genetic errors. Consequently, these effects could lead to a subsequent reduction in lung cancer risk.

In an editorial on the research in the same issue of the journal, York E. Miller, M.D., of the Denver Veterans Affairs Medical Center, and Robert L. Keith, M.D., of the University of Colorado Cancer Center, Denver, wrote:

"Although the data at present are certainly not definitive, inhaled corticosteroids deserve further consideration for lung cancer chemoprevention. Adequately powered, prospective, controlled trials with prolonged follow-up to capture effects on a carcinogenic process that progresses over years will ultimately be needed to determine efficacy. If these could be designed to capture outcomes of interest relevant to both lung cancer and COPD, joint funding by the National Cancer Institute and the National Heart Lung Blood Institute would then be desirable."

"The risk reduction suggested by the studies discussed would be a clinically significant achievement, particularly in light of the continued lung cancer epidemic," the editorialists continued. "Many additional agents are undergoing evaluation for lung cancer chemoprevention, including micronutrients, tyrosine kinase inhibitors, and blockers or agonists of signaling pathways as reviewed. It is hoped, within the next decade, that chemoprevention of lung cancer in high-risk individuals (beyond smoking cessation) will be standard in pulmonary and primary care settings as is influenza vaccination or cardiac risk factor modification. The potential for benefit is just as great."

American Thoracic Society