ArticleThe journal of trauma and acute care surgery2017
Mitochondrial DNA damage associated molecular patterns in ventilator-associated pneumonia: Prevention and reversal by intratracheal DNase I.
Article in The journal of trauma and acute care surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04445285 (Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure), which is not on this map. Cited by 23 papers, 1 of them a synthesis 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.
Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Pooled it
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 2: implementation strategies.Frontiers in transplantation · 2025Review
- Mitochondria of lung venular capillaries mediate lung-liver cross talk in pneumonia.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Mitochondria as mediators of systemic inflammation and organ cross talk in acute kidney injury.American journal of physiology. Renal physiology · 2022Review
- Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal.Military Medical Research · 2021Article
- Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Mitochondrial Fission Mediated Cigarette Smoke-induced Pulmonary Endothelial Injury.American journal of respiratory cell and molecular biology · 2020Article
- The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach.Life sciences · 2020Review
- PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort.JCI insight · 2020Article
- Plasma Transfusion Products and Contamination with Cellular and Associated Pro-Inflammatory Debris.Journal of the American College of Surgeons · 2019Article
- Can We DAMPen the Cross-Talk between the Lung and Kidney in the ICU?American journal of respiratory and critical care medicine · 2018Article
- The Role of Danger Signals in the Pathogenesis and Perpetuation of Critical Illness.American journal of respiratory and critical care medicine · 2018Review
- Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA.Scientific reports · 2018Article
- Immunothrombotic Activity of Damage-Associated Molecular Patterns and Extracellular Vesicles in Secondary Organ Failure Induced by Trauma and Sterile Insults.Frontiers in immunology · 2018Review
- Peritoneal cavity lavage reduces the presence of mitochondrial damage associated molecular patterns in open abdomen patients.The journal of trauma and acute care surgery · 2017Observational
- New and revisited approaches to preserving the reperfused myocardium.Nature reviews. Cardiology · 2017Review
Corrections and comments
- Commented on by
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPrevious studies in isolated perfused rat lungs have revealed that endothelial barrier disruption after intratracheal administration of Pseudomonas aeruginosa (strain 103; PA103) only occurs after accumulation of extracellular mitochondrial DNA (mtDNA) damage-associated molecular patterns (DAMPs) in the perfusate and is suppressed by addition of DNase to the perfusion medium. Herein, we tested the hypothesis that intratracheal DNase-a route of administration readily translatable to patient with ventilator-associated pneumonia (VAP)-also enhances degradation of mtDNA and prevents bacteria-induced lung injury.
methodsIntratracheal DNase was administered to isolated rat lungs either before or after intratracheal challenge with PA103 to determine if bacteria-induced mtDNA DAMP-dependent lung injury could be prevented or reversed by enhanced mtDNA degradation. To explore whether this concept is translatable to patients with VAP, consecutive patients suspected of VAP were prospectively enrolled. All patients suspected of VAP received a bronchoalveolar lavage (BAL) with quantitative culture for the diagnosis of VAP. Mitochondrial and nuclear DNAs were measured from the BAL. MtDNA DAMPs (i.e., ND6) were measured from serum at time of suspected diagnosis and at 24 to 48 hours afterward.
resultsIntratracheal PA103 caused significantly increased the vascular filtration coefficient (Kf) and perfusate mtDNA DAMPs. In contrast, lungs pretreated or posttreated with intratracheal DNase were protected from increases in Kf and mtDNA DAMPs. Patients with the diagnosis of VAP had significantly higher mtDNA DAMPs in the BAL (248.70 ± 109.7 vs. 43.91 ± 16.61, p < 0.05, respectively) and in the serum at 24 hours (159.60 ± 77.37 vs. 10.43 ± 4.36, p < 0.05; respectively) when compared with patients that did not have VAP.
conclusionThese findings in isolated perfused rat lungs and a cohort of severely injured patients reveal an association between bacterial pneumonia and accumulation of mtDNA DAMPs in the lung and serum. Furthermore, administration of intratracheal DNase I prevented and reversed pulmonary endothelial dysfunction evoked by PA103.
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.