© 2008 American Thoracic Society
Inhaled Corticosteroids Might Not Protect against Lung CancerTo the Editor:We read with interest the cohort study by Dr. Parimon and colleagues (1), which suggested a reduced risk of lung cancer among patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS). As lung cancer is the most common cause of death among patients with COPD (2–5), it might be tempting to consider ICS for chemoprevention of lung cancer. However, there may be a few concerns. A major concern was the limited number of ICS users included in the cohort study (1). In using ICS dose as a continuous categorical variable, it is conceivable that a minor decrease in lung cancer events among higher-dose ICS users, either by chance or by virtue of death from other causes, could generate an apparent protection of ICS against lung cancers by its high leverage. Another concern was the lack of a definite dose–response relationship shown by the study (1). A considerable lag period is expected between onset of early precancerous lesions (where ICS is postulated to act) and detection of lung cancer. However, the median time interval for detecting lung cancer was only 1.4 years. If we assume that current usage of ICS indicates chronic usage, it might be better to study ICS usage itself, rather than the much less stable dosage. Based on Parimon and coworkers' original data, Table 1 shows that lung cancer rates are similar for nonusers and all ICS users combined, with lower-dose ICS users actually demonstrating a higher rate than nonusers.
The investigators emphasized a similar point estimate in the adjusted hazard ratio (around 0.4) for the higher-dose ICS, despite modifying various conditions in their analysis. Again, the small number of ICS users might limit the robustness of multivariable analysis. If the protective effect were indeed so early and strong for ICS doses equivalent to 1,200 µg or more of triamcinolone per day, it would probably have been detected by a recent randomized controlled trial involving more than 3,000 patients receiving fluticasone 1,000 µg (equivalent to 4,000 µg of triamcinolone) daily, with or without salmeterol, followed up for 3 years (6).
Department of Health FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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