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Fabien Maldonado, MD; James R. Jett, MD; Paul A. Decker, MSc
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From the Department of Pulmonary and Critical Care Medicine (Dr Maldonado), Mayo Clinic College of Medicine; and Thoracic Diseases (Dr Jett), and Biostatistics (Mr Decker), Mayo Clinic.

Correspondence to: Fabien Maldonado, MD, Department of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, 200 1st St SW, Rochester, MN 55905; e-mail: Maldonado.Fabien@mayo.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):1259-1260. doi:10.1378/chest.11-0011
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To the Editor:

We appreciate Dr Smith’s very insightful comments on our data recently published in CHEST (December 2010)1 on the relationship between radiographic evidence of emphysema and risk of lung cancer. As mentioned, our results contrast with those of two independent retrospective studies using qualitative or semiquantitative visual assessment of emphysema as opposed to the automated CT scan quantification based on threshold detection techniques used in our study.2,3

The conventional wisdom is that, in the majority of cases, continuous data should be analyzed as continuous because conversion to categoric variables will almost systematically result in loss of power. As such, we analyzed the quantity of emphysema as a risk factor for lung cancer as a continuous variable, with adjunct analyses of emphysema as a discrete variable. We agree, however, that should an all-or-none effect of emphysema on lung cancer risk be confirmed, analyzing our data as a dichotomous variable (emphysema vs no emphysema) could theoretically make sense and could unmask a signal not otherwise evident. Indeed, the crude OR calculated by Dr Smith using a threshold of 5% is 1.7 (1.0-2.9). The use of a density threshold method makes a comparison between emphysema and nonemphysema groups impossible (because having no voxel < −900 Hounsfield units is improbable in any data set), but using an arbitrarily defined threshold of 5%, the adjusted OR is 1.85 (1.05-3.26), P = .034.

This result seems to support Dr Smith’s suggestion and would be consistent with previously published results by Wilson et al3 (whose data do suggest an absence of “dose-effect” between emphysema and lung cancer) and de Torres et al2 (who analyzed radiographic evidence of emphysema as a dichotomous variable). Another explanation for this result could be that reclassifying subjects with <5% emphysema as “no emphysema” improves the signal/noise ratio by eliminating a number of false positives (subjects without emphysema but with the presence of low-density voxels “read” as emphysema by our automated emphysema quantification system). Obviously, this result may also be spurious, a consequence of multiple hypothesis testing, or the result of chance alone.

Automated quantitative analysis of emphysema is a powerful tool, yet it still requires standardization. However, it does eliminate the risk of observer bias, a potential issue with the two mentioned studies. We agree that the relationship between radiographic evidence of emphysema and risk of lung cancer remains to be clarified, and that further research, using both visual assessment and automated CT scan quantification, is warranted.

Maldonado F, Bartholmai BJ, Swensen SJ, Midthun DE, Decker PA, Jett JR. Are airflow obstruction and radiographic evidence of emphysema risk factors for lung cancer? A nested case-control study using quantitative emphysema analysis. Chest. 2010;1386:1295-1302. [CrossRef] [PubMed]
 
de Torres JP, Bastarrika G, Wisnivesky JP, et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest. 2007;1326:1932-1938. [CrossRef] [PubMed]
 
Wilson DO, Weissfeld JL, Balkan A, et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med. 2008;1787:738-744. [CrossRef] [PubMed]
 

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References

Maldonado F, Bartholmai BJ, Swensen SJ, Midthun DE, Decker PA, Jett JR. Are airflow obstruction and radiographic evidence of emphysema risk factors for lung cancer? A nested case-control study using quantitative emphysema analysis. Chest. 2010;1386:1295-1302. [CrossRef] [PubMed]
 
de Torres JP, Bastarrika G, Wisnivesky JP, et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest. 2007;1326:1932-1938. [CrossRef] [PubMed]
 
Wilson DO, Weissfeld JL, Balkan A, et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med. 2008;1787:738-744. [CrossRef] [PubMed]
 
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