Lee JS, et al. • Predictors of Treatment Response in Patients with COPD Table 4. Multiple linear regression models for pulmonary function response to 3 months of treatment with salmeterol/fluticasone Variables β 95% CI R FEV1 change (% predicted) Constant 8.98 2.70-15.22 0.578 Wheezing history 3.54 1.18-5.90 Pre-bronchodilator FEV1 (% predicted) -0.13 -0.22--0.04 Post-bronchodilator FEV1 change (% predicted) 0.55 0.26-0.84 Low attenuation area (%) -0.09 -0.18--0.01 FVC change (% predicted) Constant 12.27 5.34-19.20 0.533 Pre-bronchodilator FVC (% predicted) -0.15 -0.23--0.06 Post-bronchodilator FVC change (% predicted) 0.55 0.34-0.76 IC/TLC (%) Constant 8.42 4.04-12.80 0.401 Pre-bronchodilator IC/TLC (%) -0.23 -0.36--0.11 Post-bronchodilator FEV1 change (% predicted) 0.34 0.10-0.58 FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity; IC/TLC, inspiratory capacity/total lung capacity; Low attenuation area, volume fraction of the lung below -950 HU at full inspiration computed tomography; β, unconditioned coefficient; CI, confidence interval. chodilator FEV1 change, and LAA were independently associat- ed with the FEV1 change after 3 months of the treatment (R = 0.578). Multiple, stepwise, linear regression analysis also showed that two variables, pre-bronchodilator FVC and post-broncho- dilator FVC change were independently associated with FVC change after the 3-month treatment (R = 0.533), and pre-bron- chodilator IC/TLC and post-bronchodilator FEV1 change were independently associated with IC/TLC change after 3 months of the treatment (R = 0.401, Table 4). DISCUSSION Our results show that wheezing history, baseline pulmonary function, bronchodilator responsiveness, and emphysema ex- tent on CT could be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. This allowed us to make a significant pre- diction model for FEV1, FVC and IC/TLC changes after 3 months of treatment. The response of pulmonary function to an ICS and a LABA in COPD patients has been well established in previous studies (4, 5). Current guidelines recommend combination of an ICS and a LABA for symptomatic COPD patients with post-bronchodilator FEV1 < 50% predicted and repeated exacerbation (1). However, clinical benefits from combination pharmacotherapy are not re- stricted to patients of severe stage of disease (18, 19). It has been difficult to predict which patients will show better responses to an ICS and a LABA. In this study, COPD patients with wheezing history, lower baseline lung function, larger bronchodilator re- sponsiveness and lower LAA on CT responded better to the treat- ment with salmeterol and fluticasone. This combination would be expected to be more effective in improving the small airway component (chronic obstructive bronchiolitis) of COPD. Wheezing is the most common symptom reported by asth- matic patients, but is also commonly reported by COPD pati- ents (20). Marini et al. (21) reported that wheezing patients with chronic airflow obstruction differed from non-wheezing pa- tients with chronic airflow obstruction by their bronchodilator DOI: 10.3346/jkms.2011.26.3.379 response. Our results showed the COPD patients with a wheez- ing history had a significantly higher mean FEV1 and FVC chang- es after bronchodilator and 3 months of treatment than those without such a history. Our study also showed a positive corre- lation between bronchodilator responsiveness (post-broncho- dilator FEV1 and FVC changes) and the FEV1 and FVC changes after 3 months of treatment. Previous studies showed that corti- costeroid reversibility in COPD patients was related to features of asthma (22). Recently, Kitaguchi et al. (23) also reported that wheezing and bronchodilator responsiveness were significant determinant for the reversibility in response to an ICS. This study also showed that COPD patients with lower pre- bronchodilator FEV1 and FVC have better responses to our com- bination treatment. On the contrary, there was no significant effect of post-bronchodilator FEV1 on the response to combina- tion treatment. A post-hoc analysis in the TORCH study showed similar results in that the severity of COPD which was assessed by post-bronchodilator FEV1 was not related to the FEV1 improve- ments after a combination treatment (19). This result might be explained as follows. The lack of a relation between COPDse- verity and treatment responsiveness may be caused by the fact that pre-bronchodilator FEV1 and post-bronchodilator FEV1 change relate to treatment responsiveness. The post-broncho- dilator FEV1 and FVC (which is unrelated to responsiveness) are the sum of the value of pre-bronchodilator FEV1 and FVC (which is related to responsiveness) and the post-bronchodila- tor FEV1 and FVC changes (which is related to responsiveness). CT provided an objective method for measuring the extent and severity of emphysema (15, 24). Several recent studies indi- cated that it is possible to separate COPD patients into emphy- sema-dominant and airway-dominant phenotypes by use of high resolution CT (HRCT) (23, 25, 26). Kitaguchi et al. (23) re- ported that lower total LAA score and the grade of bronchial wall thickening were significant determinants for bronchodila- tor responsiveness and for the responsiveness to the treatment with an ICS. However, other two studies found no significant dif- ferences in bronchodilator responsiveness among groups clas- sified according to severity of emphysema (25, 26). Previously, http://jkms.org 383