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Effect of roflumilast on quality of life, lung function and mucus characteristics in patients with non-cystic fibrosis bronchiectasis: a cross-over, unicentric, double-blind and placebo-controlled study


Bronchiectasis is a chronic disease characterized by the destruction of the structural components of the bronchial wall and consequent irreversible dilation of the bronchi. Its prevalence has increased in recent years but it is not known whether the number of patients with bronchiectasis has increased or whether there has been a greater diagnosis of the disease due to the wider use of high resolution computed tomography (HRCT) in medicine. Among the causes of bronchiectasis non-cystic fibrosis (non-CF), we can mention post-infectious, autoimmune diseases, immunodeficiencies, ciliary diseases and idiopathic abnormalities (30-50%). It is manifested as dyspnea, chronic cough, with frequent production of secretion and recurrent respiratory infections. The diagnosis is made with HRCT and subsequent etiological investigation. Although relatively common, bronchiectasis is considered an orphan disease as there is little strong evidence for adequate treatment, most of the therapeutic options are extrapolated from studies with patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). The treatment with greater evidence is the use of macrolides, especially azithromycin due to the dosage easiness. Roflumilast is a phosphodiesterase-4 inhibitor with an anti-inflammatory effect in vitro and in vivo due to the inhibition of cyclic adenosine monophosphate (cAMP) to its inactive phosphodiesterase form. As this is an enzyme expressed in high concentrations in leukocytes and other inflammatory cells responsible for the pathogenesis of pulmonary diseases such as COPD, it has been studied and used for this disease. Since bronchiectasis and COPD are chronic inflammatory diseases, they have similar inflammatory processes, it is expected that the use of roflumilast also has an anti-inflammatory effect in bronchiectasis. In addition, since bronchiectasis is a disease with poor evidence for pharmacological treatment, it is necessary to search for new therapeutic possibilities.A double-blind, placebo-controlled clinical trial with a total of 30 patients from the bronchiectasis non-cystic fibrosis outpatient clinic of the Pulmonology Division of the Hospital das Clínicas of the São Paulo Medical School (HCFMUSP) will be conducted. The sample calculation was based on the preliminary results of an ongoing study in Korea that showed improvement in quality of life in patients who used roflumilast. Patients will be randomized to intervention group, who will receive roflumilast at a dose of 500mcg on alternate days for 4 weeks, then increase the dose to 500mcg 1x a day for another 8 weeks, and placebo group, who will receive tablets similar to the medication tested, including in the dosage previously explained. After 12 weeks of follow-up, there will be a 2-week washout period and subsequent exchange of the medication received for a further 12 weeks of follow-up, for a total of 26 weeks. (AU)