Trial reportAmerican journal of respiratory and critical care medicine2014
An aberrant leukotriene A4 hydrolase-proline-glycine-proline pathway in the pathogenesis of chronic obstructive pulmonary disease.
Trial report in American journal of respiratory and critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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
43 citing papers in PubMed, 54 citations in OpenAlex.
- Genome-Wide Association Analysis of Single-Breath DlAmerican journal of respiratory cell and molecular biology · 2019Trial
- A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2015Trial
- Extracellular Matrix-Derived Matrikines: Circulating Peptides as Candidate Mediators of Lung-to-Brain Signaling.International journal of molecular sciences · 2026Review
- Rationale and Design of the Alpha-1 Biomarkers Consortium Study.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- What every clinician should know about inflammation in COPD.ERJ open research · 2024Review
- Protease-armed, Pathogenic Extracellular Vesicles Link Smoking and Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2023Article
- LC-MS/MS method for proline-glycine-proline and acetylated proline-glycine-proline in human plasma.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Diet as a Source of Acrolein: Molecular Basis of Aldehyde Biological Activity in Diabetes and Digestive System Diseases.International journal of molecular sciences · 2023Review
- Review
- Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023Article
- Substrate-dependent modulation of the leukotriene AScientific reports · 2022Article
- Extracellular Vesicles as Central Mediators of COPD Pathophysiology.Annual review of physiology · 2022Review
- Revealing lncRNA Biomarkers Related to Chronic Obstructive Pulmonary Disease Based on Bioinformatics.International journal of chronic obstructive pulmonary disease · 2022Article
- Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets.Pharmaceutics · 2021Review
- Our evolving view of neutrophils in defining the pathology of chronic lung disease.Immunology · 2021Review
- Leukotriene AFrontiers in immunology · 2020Article
- The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS.Respiratory research · 2019Observational
- Proline-Glycine-Proline Peptides Are Critical in the Development of Smoke-induced Emphysema.American journal of respiratory cell and molecular biology · 2019Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles Decrease Lung Injury in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Benzyloxycarbonyl-proline-prolinal (ZPP): Dual complementary roles for neutrophil inhibition.Biochemical and biophysical research communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
rationaleChronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated.
objectivesWe investigated changes to the leukotriene A4 hydrolase (LTA4H)-proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD.
methodsA/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis. Two human cohorts were used to analyze changes to the LTA4H-PGP pathway in never smokers, control smokers, COPD smokers, and COPD former smokers. PGP/AcPGP and LTA4H aminopeptidase activity were detected by mass spectroscopy, LTA4H amounts were detected by ELISA, and acrolein was detected by Western blot. MEASUREMENTS AND MAIN
resultsMice exposed to cigarette smoke developed emphysema with increased PGP, neutrophilic inflammation, and selective inhibition of LTA4H aminopeptidase, which ordinarily degrades PGP. We recapitulated these findings in smokers with and without COPD. PGP and AcPGP are closely associated with cigarette smoke use. Once chronic inflammation is established, changes to LTA4H aminopeptidase remain, even in the absence of ongoing cigarette use. Acrolein modifies LTA4H and inhibits aminopeptidase activity to the same extent as cigarette smoke.
conclusionsThese results demonstrate a novel pathway of aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be intimately involved in disease progression in the absence of ongoing cigarette smoke exposure. We highlight a mechanism by which acrolein potentiates neutrophilic inflammation through selective inhibition of LTA4H aminopeptidase activity. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).
Indexed as
Identifiers
What OpenQuestion holds
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.