Trial reportAmerican journal of respiratory and critical care medicine2015
A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.
Trial report in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 4 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2020Pooled it
- Effect of roflumilast on chronic obstructive pulmonary disease: a systematic review and meta-analysis.Irish journal of medical science · 2018Pooled it
- Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2017Pooled it
- Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta-analysis.Respiratory research · 2016Pooled it
- Association of Lung Quantitative CT Scan Textures With Systemic Inflammation and Mortality in COPD.Chest · 2025Article
- Rationale and Design of the Alpha-1 Biomarkers Consortium Study.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- Immunomodulatory Effects of Fluoroquinolones in Community-Acquired Pneumonia-Associated Acute Respiratory Distress Syndrome.Biomedicines · 2024Review
- Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome.International journal of molecular sciences · 2023Article
- cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features.Biochemistry and biophysics reports · 2023Review
- Review
- Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets.Pharmaceutics · 2021Review
- The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications.Heart, lung & circulation · 2021Review
- Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.Frontiers in pharmacology · 2021Review
- Extracellular matrix-derived peptides in tissue remodeling and fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- Roflumilast in Severely Ill Patients with Chronic Obstructive Pulmonary Disease with Frequent Exacerbations: Risk of Pneumonia Hospitalization and Severe Exacerbations.Journal of clinical medicine · 2020Article
- Role of phosphodiesterase-4 inhibitors in chronic obstructive pulmonary disease.The Korean journal of internal medicine · 2020Review
- Abnormal pro-gly-pro pathway and airway neutrophilia in pediatric cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
- Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.Frontiers in pharmacology · 2020Article
- The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.Respiratory research · 2019Observational
- NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma.Frontiers in immunology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleRoflumilast 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.
objectivesWe hypothesized that roflumilast would decrease AcPGP, halting the feed-forward cycle of inflammation.
methodsWe 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
resultsTwenty-seven patients were enrolled in the intention-to-treat analysis. Roflumilast treatment decreased sputum AcPGP by more than 50% (P < 0.01) and prolyl endopeptidase by 46% (P = 0.02), without significant improvement in leukotriene A4 hydrolase activity compared with placebo. Roflumilast also reduces other inflammatory markers. There were no significant changes in lung function, quality of life, or exercise tolerance between roflumilast- and placebo-treated groups.
conclusionsRoflumilast reduces pulmonary inflammation through decreasing prolyl endopeptidase activity and AcPGP. As expected for lower AcPGP levels, markers of neutrophilic inflammation are blunted. Inhibiting this self-propagating pathway lessens the overall inflammatory burden, which may alter the natural history of COPD, including the risk of exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT 01572948).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.