© 2008 American Thoracic Society doi: 10.1164/rccm.200806-902ED
The Partners—Airflow Obstruction, Emphysema, and Lung Cancer
Jonsson Comprehensive Cancer Center Lung cancer is the world's leading cause of cancer death. Many recent investigations focus attention on the molecular pathogenesis of the disease, risk assessment, and chemoprevention (1). Advances in clinical and genetic risk assessment for lung cancer are central to the progress of research in the areas of pathogenesis and chemoprevention. Although chronic obstructive pulmonary disease (COPD) has long been well established to be associated with lung cancer risk (2), it is not yet known which aspects of this risk can be attributed to cooperative or shared genetic susceptibility and/or activation of inflammatory pathways. In this issue of the Journal (pp. 738–744), Wilson and colleagues provide additional, important information regarding the association of radiographic emphysema and airflow obstruction with lung cancer (3).
The article by Wilson and coworkers is interesting from several perspectives. First, they confirm a previous report (4) that showed that the presence of emphysema detected by a screening low-dose thoracic computed tomography (CT) is a risk factor for lung cancer independent of smoking history and airflow obstruction. It is also noteworthy that a large proportion (42.6%) of the study subjects of middle-aged to elderly current or former smokers (>10 cigarettes/d for Wilson and colleagues used visual semiquantitative assessment to score emphysema severity (3). Quantitative CT is less operator dependent than visual grading of the severity of emphysema, and appears to provide a more accurate and reproducible assessment of emphysema when comparing CT results with macroscopic pathology (6). With the advent of high-resolution volumetric CT, the airways are also amenable to quantitative analysis, and CT has become the technique of choice for characterizing COPD in vivo. Although Wilson and colleagues did not observe sex differences in lung cancer risk, sex was significantly associated with visual scores of emphysema on CT. This may be due to a sex-based differential phenotype of COPD, because CT studies suggest that men appear to exhibit more emphysema at all stages of COPD than women (7, 8). Airflow limitation in COPD is caused by a mixture of parenchymal destruction (emphysema) and airway obstruction (obstructive bronchiolitis). Pathologic studies have informed the pathogenesis of COPD by showing that small airways of 2 mm internal diameter or less (ranging from the 4th to 14th airway generations) are a major site of airway obstruction due to the effects of remodeling and thickening of the airway walls and luminal occlusion by mucus and inflammatory exudates (9). Using contemporary volumetric CT, airways to the eighth generation can be segmented. Quantitative analysis has been used to derive reproducible measures of airway disease on bronchi as small as 2 mm. Several investigators have found significant correlations between physiologic airflow obstruction and both airway wall thickness and airway luminal area (10, 11). These correlations increase as airway size decreases (10). No formal studies have been done to assess the relationships between lung cancer and radiographic evidence of airway abnormalities, but it is possible that such relationships exist, given the greater tendency of airway abnormalities to accompany physiologic obstruction in women. Such studies will be important to more fully characterize COPD and the individual contributions of emphysema and airway obstruction to lung cancer risk. In keeping with the authors' highlighting of inflammation as a potential central shared pathway in the pathogenesis of COPD and lung cancer, recent studies emphasize the integral role of inflammation in this relationship (12). Particularly intriguing is the possible lung cancer chemopreventive capacity of agents that limit inflammation in patients with COPD (13). Although significant questions remain, the work by Wilson and colleagues adds to the body of knowledge requisite for advances in clinical, imaging, and genetic risk assessment for lung cancer. Radiographic evidence of emphysema as well as airflow obstruction will be a topic for further investigation in the assessment of lung cancer risk. Of particular interest will be those studies that incorporate clinical (14), inflammatory (15), genetic (16), and imaging parameters for lung cancer risk assessment. FOOTNOTES Conflict of Interest Statement: S.M.D. serves on the Scientific Advisory Board for Tragara Pharmaceuticals; he attended a meeting sponsored by AstraZeneca and was reimbursed for travel in 2008. D.R.A. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.P.T. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.T.M. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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25 yr) met spirometric criteria for COPD and that a similar proportion (42.5%) of this study cohort had visually scored CT evidence of at least trace emphysema. Although only a minority (11%) of the subjects with emphysema had no airflow obstruction, a majority (62.6%) of those with airflow obstruction had emphysema. These findings indicate a higher burden of COPD, in general, and of emphysema, in particular, than has been recognized among middle-aged to older long-term smokers/ex-smokers (
