Low-dose Theophylline as Anti-inflammatory Enhancer in Severe Chronic Obstructive Pulmonary Disease

The main objective of the study is to determine the effects of low-dose oral theophylline added to combination treatment with long-acting β-agonist (LABA) and inhaled corticosteroid (ICS) in patients with severe Chronic Obstructive Pulmonary Disease (COPD) on the rate of exacerbations defined as increase of symptoms that requires a change of medication (antibiotics and/or systemic glucocorticoid) or hospitalisation. DESIGN: Phase III multicenter, randomized, placebo-controlled, double blind, parallel, prospective study. Patient will be recruited during an hospitalisation due to COPD exacerbation and randomised at the time of discharge to receive theophylline 100 mg or placebo on top of combination therapy with inhaled corticosteroids and long-acting beta agonist. The rate of exacerbations will be determined every three months up to one year follow-up. Cl inic visits: every 3 months (total number of clinic visits = 4). In each of them, the following information will be obtained: * Number/severity of exacerbations or hospitalisation since last clinic visit * Compliance and side effects * Blood sample * Plasma levels of theophylline * Sputum (induced) * MMRC * SGRQ * Forced spirometry + inspiratory capacity \- At the beginning and at the end of the study * 6MWT * BMI * BODE