Lee JS, et al. • Predictors of Treatment Response in Patients with COPD inhalation of salbutamol (400 µg) through a metered-dose in - haler (MDI) with a spacer. Lung volumes were measured by body plethysmography (V6200; SensorMedics, or PFDX). Diffusing capacity for carbon monoxide (DLco) was measured by the sin- gle-breath method using a Vmax229D (Sensor-Medics) or a Mas- terlab Body (Jaeger AB, Würtsburg, Germany). The predicted values of FEV1, forced vital capacity (FVC), FEV1/FVC and DLco were calculated from Korean equations formulated using data from a healthy non-smoking population (11, 12). The predicted values of lung volumes were calculated from ECSC equations (13). All pulmonary function tests were performed as recom- mended by the American Thoracic Society/European Respira- tory Society (ATS/ERS). Computed tomography Volumetric CT scans were performed using 16-slice multi-de- tector CT (MDCT) scanners, according to previous described scanning protocols (14). Image data were stored in the Digital Imaging and Communications in Medicine (DICOM) format. Using in-house software, images of the whole lung were extract- ed automatically and the attenuation coefficient of each pixel was measured and calculated. The cutoff level between normal lung density and a low-attenuation area (LAA) was defined as -950 HU (15). From the CT data, the volume fraction of the lung below -950 HU (V950) was calculated automatically. The airway dimensions, wall area (WA), lumen area (LA) and wall area per- cent (WA%, defined as WA/[WA + LA] × 100), were measured near the origin of two segmental bronchi (right apical and left apico-posterior) selected by a consensus reading of two radiol- ogists. The software automatically detects the airway lumen and the inner and outer boundaries of the airway wall by use of a full- width-half-maximum (FWHM) method (16). The mean value of each segmental bronchus was used for analysis. Statistical analysis To investigate factors associated with the initial maximal posi- tive pulmonary function response to 3 months of treatment with salmeterol/fluticasone, changes in pre-bronchodilator FEV1, FVC and inspiratory capacity (IC)/total lung capacity (TLC) be- fore and after 3 months were used as the dependent variable in univariate and multivariate analyses. The FEV1 and FVC chang- es were expressed as % of predicted normal values (% predict- ed) to avoid the potential problem that baseline FEV1 and FVC appear to influence on FEV1 and FVC changes if expressed as % of baseline (17). Selected independent variables were sex, age, body mass index (BMI), chronic bronchitis history, wheezing history, smoking status (current or ex-smokers, smoking pack- years), pulmonary function parameters and CT parameters. For data had a normal distribution, we used Student’s t-test or a one- way analysis of variance (ANOVA) for categorical variables. For data that had a non-normal distribution, we used Mann-Whit- DOI: 10.3346/jkms.2011.26.3.379 ney U test or the Kruskall-Wallis test for categorical variables. Relationships between two continuous variables were examined by Pearson’s correlation analysis. The prediction models for pul- monary function response to 3 months of treatment with sal- meterol/fluticasone were constructed from multiple, stepwise, linear regression models. All statistical analyses were performed with the SPSS statistical package (version 12.0, SPSS Inc, Chica- go, IL, USA), and P values less than 0.05 were considered signif- icant. Ethics statement This study was approved by the Asan Medical Center institu- tional review board (Approval No. 2005-0345) and institution review boards of other10 hospitals. Written informed consent was obtained from all patients. RESULTS Patient characteristics Table 1 lists the baseline characteristics of the 127 COPD pati- ents. Of the enrolled patients, 123 (97%) were male. Mean age was 65.5 (SD: 7.6) yr, and mean smoking history was 46.3 (20.7) pack years. A total of 74 patients were classified as GOLD II (mod- erate COPD), 46 as GOLD III (severe COPD), and 7 as GOLD IV (very severe COPD). Ninety-one percent of subjects indicated that they had taken over 80% of the recommended medication dose. Table 1. Baseline characteristics of patients (N = 127) Parameters Age (yr) Male:female Body mass index (kg/m2) Current smoker:ex-smoker Smoking history (pack-years) Atopic:non-atopic (missing = 15) Pre-bronchodilator FEV1 (L) Pre-bronchodilator FEV1 (% predicted) Pre-bronchodilator FVC (L) Pre-bronchodilator FVC (% predicted) Pre-bronchodilator FEV1/FVC (%) Post-bronchodilator FEV1 change (L) Post-bronchodilator FVC change (L) TLC (% predicted) VC (% predicted) IC/TLC (%) FRC (% predicted) RV (% predicted) DLco (% of predicted) Low attenuation area (%) Wall area (%) Mean (SD) 65.5 (7.6) 123:4 23.4 (3.3) 48:79 46.3 (20.7) 8:104 1.49 (0.50) 47.9 (14.1) 3.22 (0.82) 75.3 (16.5) 46.4 (10.3) 0.170 (0.133) 0.278 (0.287) 105.6 (18.9) 92.7 (20.0) 32.2 (0.1) 131.7 (33.3) 133.4 (52.5) 74.6 (25.8) 20.2 (14.5) 66.2 (5.0) FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity; TLC, total lung capacity; VC, vital capacity; IC, inspiratory capacity; FRC, functional residual capacity; RV, residual volume; DLco, diffusing capacity for carbon monoxide; Low attenuation area, volume fraction of the lung below -950 HU at full inspiration computed tomo- graphy; Wall area, wall area/(wall area + lumen area) on computed tomography. http://jkms.org 381