Blast Lung Injury Research Articles

Single-cell proteomics delineates murine systemic immune response to blast lung injury

Victims of explosive events frequently suffer from blast lung injuries. Immune system has been implicated in the pathogenesis of this disease. However, systemic immune responses underlying the progression and recovery of injury repair remain poorly understood. Here, we depict the systemic landscape of immune dysregulation during blast lung injury and uncover immune recovery patterns. Single-cell analyses reveal dramatic changes in neutrophils, macrophages, monocytes, dendritic cells, and eosinophils after a gas explosion, along with early involvement of CD4 T, CD8 T, and Th17 cells. We demonstrate that myeloid cells primarily exert functions during the acute phase, while the spleen serves as an alternative source of granulocytes. Granulopoiesis is initiated in the bone marrow at a later stage during blast lung injury recovery, rather than at the acute stage. These findings contribute to a better understanding of the pathogenesis and provide valuable insights for potential immune interventions in blast lung injury.

The dynamic response of human lungs due to underwater shock wave exposure.

Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the most vulnerable organs, namely the lungs, existing criteria are highly variable due to insufficient human data and the corresponding inability to understand the underlying injury mechanisms. This study presents an experimental characterization of isolated human lung dynamics during simulated exposure to underwater shock waves. We found that the large acoustic impedance at the surface of the lung severely attenuated transmission of the shock wave into the lungs. However, the shock wave initiated large bulk pressure-volume cycles that are distinct from the response of the solid organs under similar loading. These pressure-volume cycles are due to compression of the contained gas, which we modeled with the Rayleigh-Plesset equation. The extent of these lung dynamics was dependent on physical confinement, which in real underwater blast conditions is influenced by factors such as rib cage properties and donned equipment. Findings demonstrate a potential causal mechanism for implosion injuries, which has significant implications for the understanding of primary blast lung injury due to underwater blast exposures.

Esophageal pressure monitoring and its clinical significance in severe blast lung injury.

The incidence of blast lung injury (BLI) has been escalating annually due to military conflicts and industrial accidents. Currently, research into these injuries predominantly uses animal models. Despite the availability of various models, there remains a scarcity of studies focused on monitoring respiratory mechanics post-BLI. Consequently, our objective was to develop a model for monitoring esophageal pressure (Pes) following BLI using a biological shock tube (BST), aimed at providing immediate and precise monitoring of respiratory mechanics parameters post-injury. Six pigs were subjected to BLI using a BST, during which Pes was monitored. We assessed vital signs; conducted blood gas analysis, hemodynamics evaluations, and lung ultrasound; and measured respiratory mechanics before and after the inflicted injury. Furthermore, the gross anatomy of the lungs 3h post-injury was examined, and hematoxylin and eosin staining was conducted on the injured lung tissues for further analysis. The pressure in the experimental section of the BST reached 402.52 ± 17.95KPa, with a peak pressure duration of 53.22 ± 1.69ms. All six pigs exhibited an anatomical lung injury score ≥3, and pathology revealed classic signs of severe BLI. Post-injury vital signs showed an increase in HR and SI, along with a decrease in MAP (p < 0.05). Blood gas analyses indicated elevated levels of Lac, CO2-GAP, A-aDO2, HB, and HCT and reduced levels of DO2, OI, SaO2, and OER (p < 0.05). Hemodynamics and lung ultrasonography findings showed increased ELWI, PVPI, SVRI, and lung ultrasonography scores and decreased CI, SVI, GEDI, and ITBI (p < 0.05). Analysis of respiratory mechanics revealed increased Ppeak, Pplat, Driving P, MAP, PEF, Ri, lung elastance, MP, Ptp, Ppeak - Pplat, and ΔPes, while Cdyn, Cstat, and time constant were reduced (p < 0.05). We have successfully developed a novel respiratory mechanics monitoring model for severe BLI. This model is reliable, repeatable, stable, effective, and user-friendly. Pes monitoring offers a non-invasive and straightforward alternative to blood gas analysis, facilitating early clinical decision-making. Our animal study lays the groundwork for the early diagnosis and management of severe BLI in clinical settings.

Profile of bomb blast injuries

Bomb blast injuries in India have unfortunately been a recurring and tragic reality, stemming from acts of terrorism and insurgency that have targeted various regions of the country. These incidents have resulted in significant loss of life, severe injuries, and lasting trauma for those affected. The impact of bomb blast injuries in India is not only physical but also psychological, affecting individuals, families, and communities at large.The injuries sustained in bomb blasts can vary in severity and type, depending on factors such as the type of explosive device used, the location of the blast, and the proximity of individuals to the explosion. Common injuries include shrapnel wounds, burns, fractures, traumatic amputations, and head injuries. The force of the blast can cause extensive damage to internal organs, leading to conditions such as blast lung injury, abdominal trauma, and hearing loss. The pattern of injuries due to bomb blast on the victims. Identification of the dead body of the deceased victims. To ascertain the distance of the victim from the blast from nature of injuries. Eardrum injuries sustained and mental trauma to live victims. To ascertain the presence of foreign bodies, primary and secondary missiles and there by assisting in investigations. The present study “The Profile of Bomb Blast Injuries’’ has been carried out in the one of the Major Medical College and Hospital in Maharashtra State. The present study has been carried out during the period of January 2003 to July 2004, During this study total cases studied were sixty nine (69), they are grouped as A &amp; B. A : - 32 cases died due to bomb blast has been meticulously studied. B: - 37 injured persons ( clinical cases) due to bomb blast has been studied in the different wardsof hospital. In the present work total 69 cases were studied by group A &amp; B i.e group A: 32 cases brought dead in the hospital, while group B:37 cases admitted in the hospital and following conclusion are derived :-1. Maximum affected persons from group A: deaths as well as from group B : clinical cases injured in bomb blast, were in the age group of 11 to 40 years. 2. Maximum cases from group A (brought dead to the hospital) as well as clinical cases from group B admitted in the hospital are much higher in males as compared to females. 3. The persons died, group A and injured cases (clinical) group B, during bomb blast in present study was mainly belong to Hindu religion as compared to other religions. 4. It was found in the present study that the persons died in bomb blast were mostly the residents of Mumbai city in comparison with those who are residing outside of Mumbai.

Explainable tele-ultrasound diagnosis of blast lung injury via incremental multimodal multistage fusion and video transformer

Blast lung injury (BLI) is a significant concern in cases of explosive events and can have severe consequences for victims. The injury is often irreversible, emphasizing the need for early symptom confirmation and intervention. Tele-ultrasound (Tele-US) is a novel approach that enables healthcare professionals to remotely interpret US images and provide diagnostic assessments, which can offer timely and accurate assessments for BLI. In this study, we propose an explainable two-stream tele-US diagnosis method for BLI, which is an incremental multimodal multistage fusion method (IM3S-Fusion). This method is the first deep learning-based diagnosis method for BLI and, specifically, the first exploration of video Transformers in this field. It integrates optical flow into US videos, enhancing model interpretability and improving diagnostic accuracy. By integrating incremental broad learning system (IBLS), IM3S-Fusion can incrementally update its parameters with new samples in a lifelong learning fashion, especially for those misdiagnosed samples. The results show its superiority in diagnosing BLI with (87.50 ± 2.76)%, (89.06 ± 2.71)%, (88.09 ± 5.26)%, (85.71 ± 7.14)% and (88.43 ± 2.24)% in accuracy, recall, precision, specificity and F1-score, respectively. Explanatory assistance including fused US video with optical flow, class activation map videos and confidence scores, is provided for doctors to facilitate their diagnosis.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics

PurposeTo identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. MethodsThis is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. ResultsObservations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. ConclusionsAnterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Identification of potentially functional circRNAs and prediction of the circRNA-miRNA-hub gene network in mice with primary blast lung injury

ObjectivesPrimary blast lung injury (PBLI) is the main cause of death in blast injury patients, and is often ignored due to the absence of a specific diagnosis. Circular RNAs (circRNAs) are becoming recognized as new regulators of various diseases, but the role of circRNAs in PBLI remain largely unknown. This study aimed to investigate PBLI-related circRNAs and their probable roles as new regulators in PBLI in order to provide new ideas for PBLI diagnosis and treatment.MethodsThe differentially expressed (DE) circRNA and mRNA profiles were screened by transcriptome high-throughput sequencing and validated by quantitative real-time PCR (qRT-PCR). The GO and KEGG pathway enrichment was used to investigate the potential function of DE mRNAs. The interactions between proteins were analyzed using the STRING database and hub genes were identified using the MCODE plugin. Then, Cytoscape software was used to illustrate the circRNA-miRNA-hub gene network.ResultsA total of 117 circRNAs and 681 mRNAs were aberrantly expressed in PBLI, including 64 up-regulated and 53 down-regulated circRNAs, and 315 up-regulated and 366 down-regulated mRNAs. GO and KEGG analysis revealed that the DE mRNAs might be involved in the TNF signaling pathway and Fanconi anemia pathway. Hub genes, including Cenpf, Ndc80, Cdk1, Aurkb, Ttk, Aspm, Ccnb1, Kif11, Bub1 and Top2a, were obtained using the MCODE plugin. The network consist of 6 circRNAs (chr18:21008725–21020999 + , chr4:44893533–44895989 + , chr4:56899026–56910247-, chr5:123709382–123719528-, chr9:108528589–108544977 + and chr15:93452117–93465245 +), 7 miRNAs (mmu-miR-3058-5p, mmu-miR-3063-5p, mmu-miR-668-5p, mmu-miR-7038-3p, mmu-miR-761, mmu-miR-7673-5p and mmu-miR-9-5p) and 6 mRNAs (Aspm, Aurkb, Bub1, Cdk1, Cenpf and Top2a).ConclusionsThis study examined a circRNA-miRNA-hub gene regulatory network associated with PBLI and explored the potential functions of circRNAs in the network for the first time. Six circRNAs in the circRNA-miRNA-hub gene regulatory network, including chr18:21008725–21020999 + , chr4:44893533–44895989 + , chr4:56899026–56910247-, chr5:123709382–123719528-, chr9:108528589–108544977 + and chr15:93452117–93465245 + may play an essential role in PBLI.

Blast Lung Injury in Children: Injury Patterns and Associated Organ Injuries.

Bombings are the most common cause of civilian deaths in wars, and unfortunately, a large proportion of civilian victims are children. This study aimed to evaluate the frequency of blast lung injury (BLI), to evaluate lung injury patterns on tomographic images, and to document the relationship between blast lung and mortality in children exposed to the blast effect. Thirty-six children (25.3% of pediatric patients brought to our hospital with blast injury) with BLI were included in the study. The pediatric trauma score evaluations made in the emergency department in the first admission were recorded. Lung injury findings in the computed tomography images of the patients were examined, and injuries detected in other systems were recorded. The most common lung injury pattern was contusion (right: 69.4%, left: 80.6%). The incidence of brain damage (52.4%) and intra-abdominal injury (76.2%) in children with low pediatric trauma score value was statistically significantly higher ( P = 0.049, P = 0.017, respectively). There was no statistically significant correlation between the presence of lung injury, injury patterns, and mortality. The incidence of brain damage in deceased patients (61.5%) was statistically significantly higher than the incidence of brain damage in surviving patients (26.1%) ( P = 0.036). Low pediatric trauma score was observed in 11 (84.6%) of the deceased children and in 10 (43.5%) of the survivors ( P = 0.016). The mean age of children with hemothorax in the right lung was statistically significantly lower than those without ( P = 0.014). Our findings revealed that pediatric BLI is common after a blast, that it is associated with other system injuries, and that a multimodal radiological approach is required in child victims.

Characteristics of inflammatory response and repair after experimental blast lung injury in rats.

Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator. Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile. After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h. Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury.

Non-penetrating combat-related thoracic trauma (review)

Combat-related thoracic trauma is a significant cause of morbidity and mortality in all military opera­tions. Penetrating, blunt, and explosive wounds are the most common mechanisms of injury. Visualization diagnosis plays a key role in the treatment. This review discusses the visualization signs of chest injuries from blunt trauma and blast trauma. Objective was to study in detail the mechanisms and visualization signs of non-penetrating combat-related thoracic trauma. 235 literature sources were found in the PubMed system by the query Thoracic AND Trauma AND Combat, 34 of which were selected for further detailed study. In modern warfare, thoracic trauma accounts for 8.6—16.0 % of casualties. Chest X-ray and CT are the visualization methods most commonly used in the evaluation of polytrauma patients from combat and peacetime. Chest X-ray can be quickly obtained in a patient with blunt trauma and emergency conditions that include tension pneumothorax, large hemothorax, chest compression, and others. Chest CT is an important component of trauma visualization. Compared to chest X-ray, chest CT identifies 20 % more pathology, and occult chest trauma due to blunt force trauma can be identified in 71 % of patients. CT provides 38—81 % additional diagnoses compared to chest X-ray.Thoracic trauma is often diagnosed in places of combat. As medical imaging technology moves closer to combat areas, this tool is becoming increasingly available to aid in the diagnosis and rapid treatment of combat-related thoracic trauma. Clinical and surgical management of the traumatized patient relies on skills learned in modern civilian training and honed in war. However, imaging of blunt and explosive injuries may be different in civilian and military settings. The distinct injury pattern and atypical imaging findings of blunt trauma and blast lung injury are important to recognize at an early stage because of the severity of this pathology and the impact of an accurate diagnosis on clinical management.We present our own observations of patients who were treated at the Military Medical Clinical Center of the Northern Region (Kharkiv) in 2022 for non­penetrating combat­related thoracic trauma.

Crosstalk between Inflammation and Hemorrhage/Coagulation Disorders in Primary Blast Lung Injury.

Primary blast lung injury (PBLI), caused by exposure to high-intensity pressure waves from explosions in war, terrorist attacks, industrial production, and life explosions, is associated with pulmonary parenchymal tissue injury and severe ventilation insufficiency. PBLI patients, characterized by diffused intra-alveolar destruction, including hemorrhage and inflammation, might deteriorate into acute respiratory distress syndrome (ARDS) with high mortality. However, due to the absence of guidelines about PBLI, emergency doctors and rescue teams treating PBLI patients rely on experience. The goal of this review is to summarize the mechanisms of PBLI and their cross-linkages, exploring potential diagnostic and therapeutic targets of PBLI. We summarize the pathophysiological performance and pharmacotherapy principles of PBLI. In particular, we emphasize the crosstalk between hemorrhage and inflammation, as well as coagulation, and we propose early control of hemorrhage as the main treatment of PBLI. We also summarize several available therapy methods, including some novel internal hemostatic nanoparticles to prevent the vicious circle of inflammation and coagulation disorders. We hope that this review can provide information about the mechanisms, diagnosis, and treatment of PBLI for all interested investigators.

Establishment and evaluation of an in vitro blast lung injury model using alveolar epithelial cells.

Gas explosion is a fatal disaster commonly occurred in coal mining and often causes systematic physical injuries, of which blast lung injury is the primary one and has not yet been fully investigated due to the absence of disease models. To facilitate studies of this field, we constructed an in vitro blast lung injury model using alveolar epithelial cells. We randomly divided the alveolar epithelial cells into the control group and blast wave group, cells in the blast wave group were stimulated with different strengths of blast wave, and cells in the control group received sham intervention. Based on the standards we set up for a successful blast injury model, the optimal modeling conditions were studied on different frequencies of blast wave, modeling volume, cell incubation duration, and cell density. The changes of cell viability, apoptosis, intracellular oxidative stress, and inflammation were measured. We found that cell viability decreased by approximately 50% at 6 h after exposing to 8 bar energy of blast wave, then increased with the extension of culture time and reached to (74.33 ± 9.44) % at 12 h. By applying 1000 ~ 2500 times of shock wave to 1 ~ 5 × 105 cells /ml, the changes of cell viability could well meet the modeling criteria. In parallel, the content of reactive oxide species (ROS), malonaldehyde (MDA), interleukin 18 (IL-18), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β) increased in the blast wave group, while superoxide dismutase (SOD) and Glutathione -S- transferase (GST) decreased, which were highly consistent with that of human beings with gas explosion-induced pulmonary injury. An in vitro blast lung injury model is set up using a blast wave physiotherapy under 8 bar, 10 Hz blast wave on (1 ~ 5) ×105 alveolar epithelial cells for 1 000 times. This model is flexible, safe, and stable, and can be used for studies of lung injury caused by gas explosion and blast-associated other external forces.

Proteomic global proteins analysis in blast lung injury reveals the altered characteristics of crucial proteins in response to oxidative stress, oxidation-reduction process and lipid metabolic process

ABSTRACT Background: Blast lung injury (BLI) is the most common fatal blast injury induced by overpressure wave in the events of terrorist attack, gas and underground explosion. Our previous work revealed the characteristics of inflammationrelated key proteins involved in BLI, including those regulating inflammatory response, leukocyte transendothelial migration, phagocytosis, and immune process. However, the molecular characteristics of oxidative-related proteins in BLI ar still lacking. Methods: In this study, protein expression profiling of the blast lungs obtained by tandem mass tag (TMT) spectrometry quantitative proteomics were re-analyzed to identify the characteristics of oxidative-related key proteins. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h and 1 w after blast exposure. The differential protein expression was identified by bioinformatics analysis and verified by western blotting. Results: The results demonstrated that thoracic blast exposure induced reactive oxygen species generation and lipid peroxidation in the lungs. Analysis of global proteins and oxidative-related proteomes showed that 62, 59, 73, 69, 27 proteins (accounted for 204 distinct proteins) were identified to be associated with oxidative stress at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. These 204 distinct proteins were mainly enriched in response to oxidative stress, oxidation-reduction process and lipid metabolic process. We also validated these results by western blotting. Conclusions: These findings provided new perspectives on blast-induced oxidative injury in lung, which may potentially benefit the development of future treatment of BLI.

Single and Multiplex Immunohistochemistry to Detect Platelets and Neutrophils in Rat and Porcine Tissues.

Platelet–neutrophil complexes (PNCs) occur during the inflammatory response to trauma and infections, and their interactions enable cell activation that can lead to tissue destruction. The ability to identify the accumulation and tissue localisation of PNCs is necessary to further understand their role in the organs associated with blast-induced shock wave trauma. Relevant experimental lung injury models often utilise pigs and rats, species for which immunohistochemistry protocols to detect platelets and neutrophils have yet to be established. Therefore, monoplex and multiplex immunohistochemistry protocols were established to evaluate the application of 22 commercially available antibodies to detect platelet (nine rat and five pig) and/or neutrophil (four rat and six pig) antigens identified as having potential selectivity for porcine or rat tissue, using lung and liver sections taken from models of polytrauma, including blast lung injury. Of the antibodies evaluated, one antibody was able to detect rat neutrophil elastase (on frozen and formalin-fixed paraffin embedded (FFPE) sections), and one antibody was successful in detecting rat CD61 (frozen sections only); whilst one antibody was able to detect porcine MPO (frozen and FFPE sections) and antibodies, targeting CD42b or CD49b antigens, were able to detect porcine platelets (frozen and FFPE and frozen, respectively). Staining procedures for platelet and neutrophil antigens were also successful in detecting the presence of PNCs in both rat and porcine tissue. We have, therefore, established protocols to allow for the detection of PNCs in lung and liver sections from porcine and rat models of trauma, which we anticipate should be of value to others interested in investigating these cell types in these species.

Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter

PurposeHigh explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. MethodsGoats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). ResultsIn total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 – 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. ConclusionThe main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.

Combat Trauma-Related Acute Respiratory Distress Syndrome: A Scoping Review.

Pubmed was searched from 1969 to April 2022. Studies were included if they examined ALI/ARDS or related entities (blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces). Study years, design, location, number of patients, target outcomes as related to ALI/ARDS or related entities, and results were collected. The initial search yielded 442 studies, with 22 ultimately included. Literature on ALI/ARDS comes mostly from retrospective data and case studies, with limited prospective studies. The incidence and prevalence of ALI/ARDS range from 3% to 33%, and mortality 12.8% to 33%. BLI, a known antecedent to ALI/ARDS, has an incidence and mortality ranging from 1.4% to 40% and 11% to 56%, respectively. Risk factors for ALI/ARDS include pulmonary injury, inhalation injury, blunt trauma, pneumonia, higher military injury severity score, higher injury severity score, higher fresh frozen plasma volumes, higher plasma and platelet volumes, the use of warm fresh whole blood, female sex, low blood pressure, and tachycardia. Literature has demonstrated the effectiveness in transportation of these patients and the utility of extracorporeal life support. ALI/ARDS incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%. ALI/ARDS has been associated with injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Studies are limited to mostly retrospective data, and more data are needed to better characterize these conditions.

Metformin mitigates gas explosion‑induced blast lung injuries through AMPK‑mediated energy metabolism and NOX2‑related oxidation pathway in rats

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

DDAH1 Promotes Lung Endothelial Barrier Repair by Decreasing Leukocyte Transendothelial Migration and Oxidative Stress in Explosion-Induced Lung Injury

Explosion-induced injury is the most commonly encountered wound in modern warfare and incidents. The vascular inflammatory response and subsequent oxidative stress are considered the key causes of morbidity and mortality among those in blast lung injury. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in explosion-induced injury remains to be explained. To explore the mechanism of vascular injury in blast lung, 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly equally divided into control group and blast group, respectively. Body weight, lung weight, and dry weight of the lungs were recorded. Diffuse vascular leakage was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and ADMA level were determined through ELISA. Hematoxylin-eosin staining and ROS detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, cell adhesion molecules and leukocyte transendothelial migration, vascular injury, endothelial barrier dysfunction, and the DDAH1/ADMA/eNOS signaling pathway. We found that DDAH1 deficiency aggravated explosion-induced body weight reduction, lung weight promotion, diffuse vascular leakage histopathological changes, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA, and IRE-1α expression. Regarding vascular endothelial barrier dysfunction, DDAH1 deficiency increased the expression of ICAM-1, Itgal, Rac2, VEGF, MMP9, vimentin, and N-cadherin, while lowering the expression of occludin, CD31, and dystrophin. DDAH1 deficiency also exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Our results indicated that explosion could induce severe lung injury and pulmonary vascular insufficiency, whereas DDAH1 could promote lung endothelial barrier repair and reduce inflammation and oxidative stress by inhibiting ADMA signaling which in turn increased eNOS activity.

Ventilating the blast lung: Exploring ventilation strategies in primary blast lung injury

Introduction Primary blast lung injury (PBLI) is the most common and fatal of all primary blast injuries. The majority of those with PBLI will require early intubation and mechanical ventilation, and thus, ventilation strategy forms a crucial part of any management plan. Methods: A comprehensive, but not systematic, PubMed and Google Scholar database search identified articles that contribute to our current understanding of ventilation strategies in PBLI for a narrative educational review. Results A PBLI ventilation strategy must strive to minimise all four of ventilator-associated lung injury (VALI), volutrauma, barotrauma and biotrauma. The three main ventilation strategies available are conventional low tidal volume (LTV) ventilation, airway pressure release ventilation (APRV) and high frequency oscillatory ventilation (HFOV). Conventional LTV ventilation together with a variable positive end-expiratory pressure (PEEP) and permissive hypercapnia has demonstrated reduced inflammation and mortality with a greater number of ventilator-free days. APRV has the potential to reduce dynamic strain, PaO2/FiO2 ratios, levels of applied mechanical power and extravascular lung water while encouraging spontaneous breathing. HFOV is able to effectively avoid VALI while curbing inflammation and histological lung injury, though not necessarily mortality. Conclusions: Presently, PBLI should largely be managed with conventional LTV ventilation alongside a variable PEEP and permissive hypercapnia with APRV and HFOV reserved as rescue strategies for where conventional LTV ventilation fails. Clinicians should additionally consider supplementing their strategy with adjunctive therapies such as prone positioning, inhaled nitric oxide and extracorporeal membrane oxygenation that may further reduce mortality and combat severe respiratory and/or cardiac failure.

A novel animal model of primary blast lung injury and its pathological changes in mice.

Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1β, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue.