our study group has shown that emphysema dominant COPD patients (LAA ≥ 20% and pre-bronchodilator FEV1 ≥ 45% pre- dicted) responded poorly to the 3 months of combination treat- ment (27). In this study, LAA had a week negative correlation with the FEV1 change after 3 months of the treatment. This re- sult might be explained as follows. For COPD patients, the ma- jor determinants of FEV1 are small airway disease and emphy- sema. If a COPD patient has a more significant emphysema com- ponent than that of small airway disease, he or she would be ex- pected to have a poorer response to pharmacologic treatments that predominantly target small airway disease. In this study, mean WA was not correlated with the FEV1 and FVC change af- ter 3 months of the treatment. A previous report showed that large airway dimension serve as a useful surrogate for small air- way remodeling (28). Nonetheless, it is possible that the lack of a significant relationship between WA and treatment response may be due to the relatively imprecise and indirect estimate of small airway wall area. There are two factors that could have po- tentially confounded our volumetric CT result. First, we used three different MDCT scanners, and different scanners may have graded the emphysema index differently. A method that cor- rects for differences between different CT scanners has not yet been established. Second, we used only two large airways to evaluate airway dimension. In this study, 19.7% of included patients had overlapping diag- noses of COPD and asthma (overlap syndrome). Those patients with overlap syndrome could affect our study results. However, subgroup analysis after excluding patients with overlap syndrome showed the similar results. Our study has two limitations. First, we did not consider airway inflammatory markers. Previous studies showed an increased number of eosinophils in bron- choalveolar lavage fluid in a subset of patients with COPD who responded to short-term administration of oral corticosteroids (29) and sputum eosinophil counts were significantly correlat- ed with reversibility in response to ICS treatment (23). If we had included airway inflammatory markers, we might have been able to develop more powerful prediction models. Second, 97% of our patients were male. Gender may have a substantial influ- ence on treatment response in COPD patients (30), so we can- not generalize our results to females. In conclusion, wheezing history, baseline pulmonary func- tion, bronchodilator responsiveness, and emphysema extent in COPD patients may be used for predicting the pulmonary func- tion response to 3 months of treatment with salmeterol/flutica- sone. Conflict of Interest Statement J. S. Lee, S.W. Ra, E. J. Chae, J-H Lee, E-K Kim, Y. K. Lee, T-H Kim, J. W. Huh, W. J. Kim, J. H. Lee, S-M Lee, S. Y. Lee, S. Y. Lim, T. R. Shin, H. I. Yoon and S. S. Sheen have no conflicts of interest to disclose. J. B. Seo has been an investigator in a government-spon- 384 http://jkms.org Lee JS, et al. • Predictors of Treatment Response in Patients with COPD sored study (2006-2008 Korea Science and Engineering Foun- dation). Y-M. Oh has been an investigator in university-sponsored studies (Asan Institute for Life Science, University of Ulsan Col- lege of Medicine) and an industry-sponsored study (MSD Ko- rea, and AstraZeneca Korea), and has participated as a speaker at scientific meetings organized and financed by various phar- maceutical companies (Handok, GlaxoSmithKline, AstraZene- ca Korea, MSD Korea, and Boehringer Ingelheim) and a maga- zine company (Korea Doctors’ Weekly). S-D. 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