ReviewPharmacology & therapeutics2009
Attacking the multi-tiered proteolytic pathology of COPD: new insights from basic and translational studies.
Review in Pharmacology & therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 45 citations in OpenAlex.
- A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2023Trial
- Nuclear Factor Erythroid 2-Related Factor 2 in Chronic Obstructive Pulmonary Disease Progression: Regulation of Macrophage Polarization and Hyaluronic Acid Metabolism.International journal of chronic obstructive pulmonary disease · 2026Article
- Article
- Pulmonary Emphysema: Current Understanding of Disease Pathogenesis and Therapeutic Approaches.Biomedicines · 2025Review
- Therapeutic effect of two strategies directed at disruption of pathogenic neutrophil extracellular vesicles in a murine emphysema model.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- An in vivo model for extracellular vesicle-induced emphysema.JCI insight · 2022Article
- Promotion of a Protease-Antiprotease Imbalance in the Airways through Chronic Vaping.American journal of respiratory and critical care medicine · 2019Article
- Review
- Article
- Angiotensin-converting enzyme defines matrikine-regulated inflammation and fibrosis.JCI insight · 2017Article
- A Unique High-Throughput Assay to Identify Novel Small Molecule Inhibitors of Chemotaxis and Migration.Current protocols in cell biology · 2017Article
- Neutrophil Fates in Bronchiectasis and Alpha-1 Antitrypsin Deficiency.Annals of the American Thoracic Society · 2016Article
- A High-Throughput, Multi-Cell Phenotype Assay for the Identification of Novel Inhibitors of Chemotaxis/Migration.Scientific reports · 2016Article
- Disease phenotyping in chronic obstructive pulmonary disease: the neutrophilic endotype.Current opinion in pulmonary medicine · 2016Review
- The soot of all evil.eLife · 2015Article
- Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection.Nature communications · 2015Article
- Neutrophils: potential therapeutic targets in tularemia?Frontiers in cellular and infection microbiology · 2013Review
- Novel mechanism of aortic aneurysm development in mice associated with smoking and leukocytes.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Cigarette smoke enhances chemotaxis via acetylation of proline-glycine-proline.Frontiers in bioscience (Elite edition) · 2012Article
- Beyond corticosteroids: future prospects in the management of inflammation in COPD.European respiratory review : an official journal of the European Respiratory Society · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Protease activity in inflammation is complex. Proteases released by cells in response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases like chronic obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven by dysregulation of protease activity, either through hyperactivity of proteases or deficiency or dysfunction their antiprotease regulators. Animal studies demonstrate the accuracy of this hypothesis through genetic and pharmacologic tools. New work shows that ECM destruction generates peptide fragments active on leukocytes via neutrophil or macrophage chemotaxis towards collagen and elastin derived peptides respectively. Such fragments now have been isolated and characterized in vivo in each case. Collectively, this describes a biochemical circuit in which protease activity leads to activation of local immunocytes, which in turn release cytokines and more proteases, leading to further leukocyte infiltration and cyclical disease progression that is chronic. This circuit concept is well known, and is intrinsic to the protease-antiprotease hypothesis; recently analytic techniques have become sensitive enough to establish fundamental mechanisms of this hypothesis, and basic and clinical data now implicate protease activity and peptide signaling as pathologically significant pharmacologic targets. This review discusses targeting protease activity for chronic inflammatory disease with special attention to COPD, covering important basic and clinical findings in the field; novel therapeutic strategies in animal or human studies; and a perspective on the successes and failures of agents with a focus on clinical potential in human disease.
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.