Unknown

Dataset Information

0

A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.


ABSTRACT: RATIONALE:Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) pathway is a novel means of neutrophilic inflammation that is pathologic in the development of COPD. AcPGP is produced by extracellular matrix collagen breakdown with prolyl endopeptidase and leukotriene A4 hydrolase serving as the enzymes responsible for its production and degradation, respectively. OBJECTIVES:We hypothesized that roflumilast would decrease AcPGP, halting the feed-forward cycle of inflammation. METHODS:We conducted a single-center, placebo-controlled, randomized study investigating 12 weeks of roflumilast treatment added to current therapy in moderate-to-severe COPD with chronic bronchitis. Subjects underwent sputum and blood analyses, pulmonary function testing, exercise tolerance, and quality-of-life assessment at 0, 4, and 12 weeks. MEASUREMENTS AND MAIN RESULTS:Twenty-seven patients were enrolled in the intention-to-treat analysis. Roflumilast treatment decreased sputum AcPGP by more than 50% (P?

SUBMITTER: Wells JM 

PROVIDER: S-EPMC4642210 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.

Wells J Michael JM   Jackson Patricia L PL   Viera Liliana L   Bhatt Surya P SP   Gautney Joshua J   Handley Guy G   King R Wilson RW   Xu Xin X   Gaggar Amit A   Bailey William C WC   Dransfield Mark T MT   Blalock J Edwin JE  

American journal of respiratory and critical care medicine 20151001 8


<h4>Rationale</h4>Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) pathway is a novel means of neutrophilic inflammation that is pathologic in the development of COPD. AcPGP is produced by extracellular matrix collagen breakdown with prolyl  ...[more]

Similar Datasets

| S-EPMC4226028 | biostudies-literature
| S-EPMC3823967 | biostudies-literature
| S-EPMC8686853 | biostudies-literature
| S-EPMC9053004 | biostudies-literature
| S-EPMC3072752 | biostudies-literature
| S-EPMC8934583 | biostudies-literature
| S-EPMC3085868 | biostudies-literature
2003-07-16 | GSE475 | GEO
| S-EPMC6699658 | biostudies-literature
| S-EPMC8247000 | biostudies-literature