Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Bronchiectasis
Status:
Unknown status
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
Although relatively common, bronchiectasis is considered an orphan disease as there is little
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). Inhaled bronchodilators and corticosteroids should be used as a therapeutic test and
maintained if there is improvement of symptoms or lung function. There is no evidence to
justify the use of mucolytic agents for these patients. The treatment with greater evidence
is the use of macrolides, especially azithromycin. A meta-analysis published in 2014 showed
that there was a reduction in the number of exacerbations, an improvement in the quality of
life and a reduction in the decrease in FEV1. However, studies have shown conflicting results
regarding quality of life and pulmonary function.
Roflumilast is a phosphodiesterase-4 inhibitor with an anti-inflammatory effect in vitro and
in vivo due to the inhibition of cyclic adenosine monopostat breakdown (cAMP) to its inactive
phosphodiesterase form. As this enzyme is 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. COPD is characterized by a chronic
inflammatory process of the airways, predominantly neutrophils and high levels of
proinflammatory cytokines related to this cell, such as interleukin-8, neutrophil elastase,
tumor necrosis factor (TNF) alpha and E-selectin. The REACT study showed that roflumilast
prevents moderate and severe infectious exacerbations in addition to improved lung function
in patients with COPD who continue to exacerbate despite the use of combined bronchodilator
and inhaled corticosteroid therapy.
Since bronchiectasis and COPD are chronic inflammatory diseases, they present similar
inflammatory processes, with neutrophil as the main inflammatory cell, 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.
Phase:
Phase 2
Details
Lead Sponsor:
University of Sao Paulo General Hospital
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo