It is a phase IV clinical trial: longitudinal, prospective, evaluator-blind, randomized into 2 groups of patients with chronic obstructive pulmonary disease (COPD). The intervention group was based on the administration of roflumilast 500 mcg per day on alternate days (roflumilast 500μg eod) for 2 weeks (phasing). In the control group assigned to undertake the treatment according to the standard dosage (roflumilast 500μg od).

The patient monitoring will be done by one of the sub-investigators fully independent team that started the medication keeping the pattern masking by single blind, and since it aims to assess the frequency of adverse events (AEs) in both groups were collected systematically different AEs and their characteristics at 15 days (V1), and from that moment a month (V2) and 2 months (V3). Likewise, other data collected (functional demographic, comorbidities, home treatment, anxiety and depression and quality of life).

The purpose of this study is to assess whether the administration of roflumilast by a gradual pattern varies the incidence of discontinuations due to adverse events when compared with the usual dosage.

Inclusion Criteria:

• Diagnosis of COPD in severe degree GOLD criteria, assessed by post-bronchodilator spirometry (FEV1 <50%, FEV1/Forced vital capacity (FVC) <70% of theory).
• Age over 18 years.
• Productive cough recurrently most days for at least three months a year and at least 2 consecutive years.
• History from smoking prior> 15 to 20 packs / year.
• An exacerbation in the previous year.
• Stability clinic in the last 30 days.

Exclusion Criteria:

• Pregnancy / breastfeeding.
• Acute infections.
• Patients with severe mental disorder or uncontrolled, in the opinion of the investigator, would make the patient has a higher risk due to their participation in the study, could be a confounding factor in the study's results or is likely to prevent that the patient meets the requirements of the study or to complete the study.
• Patients cachectic or the risk of cachexia.
• HIV infection.
• Severe immune Infections (systemic lupus erythematosus, multiple sclerosis, etc.).
• Gastroesophageal reflux symptoms and diagnosis established.
• Hiatal hernia.
• Peptic ulcer disease.
• Inflammatory bowel pathology.
• Neoplastic pathology: current diagnosis of cancer other than basal cell or squamous cell carcinoma of the skin.
• Moderate to severe hepatic impairment (Child-Pugh BC).
• Inability to understand / perform the techniques.
• Home treatment with theophylline, methotrexate, azathioprine, infliximab, etanercept, inducers of cytochrome P450 (eg, rifampicin, phenobarbital, carbamazepine, phenytoin),cytochrome P450 3A4 (CYP3A4) inhibitors (erythromycin and ketoconazole), oral contraceptives (gestodene and ethinyl estradiol), making prolonged oral corticosteroids, or a drug that contains fluvoxamine, enoxacin and cimetidine.