Investigation of steroid responsiveness in patients with chronic obstructive pulmonary disease

INTERVENTION: 188 patients with COPD, GOLD groups B‐D, are recruited within 18 months. Based on the histological analysis of endobronchial biopsies taken by flexible bronchoscopy, patients are divided into two groups. Group A includes patients with ASMC area >20% and group B includes patients with ASMC area =20%. All patients follow a run‐in period of 6 weeks on open‐label triple therapy with LAMA (aclidinium 400 mcg, bid), LABA (formoterol 12 mcg, bid) and ICS (budesonide 400 mcg, bid). Subsequently, patients from each group are randomized (1:1) to receive either: 1. Triple treatment with LAMA, LABA and ICS (groups A1 and B1) or 2. Combined bronchodilator therapy with LAMA and LABA and placebo for ICS (groups A2 and B2) Randomization will be stratified by group (A vs B), follow a block size of 4. The duration of treatment will be 12 months, with follow‐up at 3, 6, 9 and 12 months after randomization. CONDITION: Chronic obstructive pulmonary disease ; Respiratory ; Chronic obstructive pulmonary disease, unspecified PRIMARY OUTCOME: To compare the differences in the mean decrease of post‐bronchodilator FEV1 in milliliters measured using a spirometer at 12 months, between patients with low (=20%) and high (>20%) ASMC area and according to whether they received ICS or not SECONDARY OUTCOME: Immediately after the run‐in phase, at 3, 6, 9 and 12 months after randomization to compare changes in:; 1. Modified Medical Research Council (MMRC) dyspnea scale; 2. COPD assessment test (CAT); 3. Health‐related quality of life, measured using SF‐36, SGRQ; 4. Pre and post bronchodilator body plethysmography/DLCO; 5. Expiratory FeNO; 6. Single and multiple‐breath N2 wash‐out; 7. Forced impulse oscillometry; 8. 6‐minute walking distance (6MWD); 9. Movement patterns, measured using accelerometry; 10. Therapy‐related side effects (oral candidiasis, tachycardia, tremor, hoarseness, pneumonia); 11. Exacerbations rate; 12. Serum biomarkers; between patients with low (=20%) and high (>20%) ASMC area and according to whether they received ICS or not INCLUSION CRITERIA: 1. Age = 40 years 2. COPD, as defined by the GOLD Guidelines and categorization in groups B‐D 3. No acute exacerbation of COPD or any respiratory infection requiring medical attention or leading to a change in medication within the last 4 weeks 4. Unchanged respiratory medication regimen within the last 8 weeks 5. At least one exacerbation in the previous year 6. Current or ex‐smokers with smoking history of = 10 pack‐years 7. Willingness to participate in a longitudinal, cohort study 8. Capability to provide written informed consent