Roflumilast Safety Administered Once a Day on Alternate Days for Two Weeks Compared to the Usual Dosage Once Daily

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.