INTRODUCTION Chronic obstructive pulmonary disease (COPD) is usually pro- gressive and is associated with an abnormal inflammatory re- sponse of the lung to noxious particles or gases (1). Previous studies have shown that regular treatment of COPD with an in- haled corticosteroid (ICS) improve pulmonary function and re- duces the frequency of exacerbations, even though it does not modify the long-term decline of forced expiratory volume in 1 sec (FEV1) (2, 3). Combination therapy with an ICS and a long acting β2-agonist (LABA) is better in improving lung function and health status, and reducing daily symptoms and exacerba- tions than single therapy (4, 5). COPD is a heterogeneous disease in terms of clinical, physi- ological, and pathological presentation. The chronic airflow lim- itation associated with COPD is caused by a variable contribu- tion of small airway disease (obstructive bronchiolitis) and pa- renchymal destruction (emphysema). Thus, the therapeutic re- sponse to combination treatment with an ICS and a LABA is also variable. Previous COPD guidelines recommended the use of short-term (two weeks) oral corticosteroid therapy to identify COPD patients who might benefit from long-term treatment with an ICS (6). However, it was recently shown that the response to a short-term oral corticosteroid is a poor predictor of the long- term response to an ICS (7). Currently, there are no known good predictors of the responsiveness of COPD patients to treatment with an ICS and a LABA. The aim of this study was to identify predictors of pulmonary function response to 3 months of treatment with salmeterol/ fluticasone in patients with COPD. MATERIALS AND METHODS Patients A total of 127 stable COPD patients who had been treated with salmeterol/fluticasone for 3 months were analyzed retrospec- tively. All patients were selected from the Korean Obstructive Lung Disease (KOLD) Cohort, which had 226 stable patients with obstructive lung disease (OLD) were prospectively recruit- ed from the pulmonary clinics of 11 hospitals in Korea from June 2005 to September 2009 (Fig. 1). The inclusion criteria for the KOLD cohort have been described elsewhere (8). COPD was diagnosed based on smoking history (more than 10 pack-years) and the presence of airflow limitation that was not fully revers- ible (post-bronchodilator FEV1/forced vital capacity [FVC] < 70% and post-bronchodilator FEV1 < 80% predicted). We included COPD patients who had wheezing history or who showed par- tial reversibility of airflow limitation after inhalation of salbuta- mol. Lee JS, et al. • Predictors of Treatment Response in Patients with COPD Study protocol Baseline clinical data were obtained after cessation of the fol- lowing respiratory medications: an ICS for 2 weeks, an inhaled LABA for 2 days, an inhaled short-acting β2-agonist or inhaled short-acting anti-cholinergic for 12 hr. The baseline clinical data included demographic data, smoking history, chronic bronchitis history, wheezing history, pulmonary function tests, chest radi- ography and volumetric computed tomography (CT). Chronic bronchitis was defined as cough and sputum production on most days for a minimum of 3 months per year for at least 2 yr (9). Wheezing history was obtained through the following ques- tion: “Have you had wheezing or whistling in your chest at any time in the last year?” (10) Atopic status was assessed by a skin prick test to 11 common allergens, with a 10% histamine and saline control. Patients were considered to be atopic if they re- acted with a wheal of larger than the histamine control for more than one of the allergens. After obtaining baseline data, patients were treated with a salmeterol/fluticasone propionate 50/500 µg dry powder inhaler twice per day for 3 months, and then spi - rometry and lung volume measurement were performed again after the morning medication. During the 3-month treatment period, only salbutamol was allowed as needed. Adherence to the treatment medication monitored and recorded by research coordinators. Pulmonary function tests Spirometry was performed using a Vmax 22 instrument (Sensor- Medics; Yorba Linda, CA, USA) or a PFDX machine (MedGraph- ics, St. Paul, MN, USA). To assess the post-bronchodilator change, spirometry was performed pre-bronchodilator and 15 min after 226 patients with obstructive lung disease Excluded 14 patients with post-bronchodilator FEV1/FVC ≥ 70% 12 patients with post-bronchodilator FEV1 ≥ 80% 17 patients with less than 10 pack-years smoking history 183 patients with COPD Excluded 13 patients who had taken tiotropium 17 patients who had taken combination of formoterol/ budesonide 26 patients who had lost follow-up at the point of 3-month treatment 127 patients with COPD who had taken combination of salmeterol/fluticasone were analyzed Fig. 1. Patients selection. 380 http://jkms.org DOI: 10.3346/jkms.2011.26.3.379