BLAST LUNG INJURY: OUR EXPERIENCE AT A TERTIARY CARE MILITARY HOSPITAL

Objective: To study the management and mortality in patients with blast lung injury at a tertiary care military hospital. Study Design: Prospective, observational study. Place and Duration of Study: Intensive Care Unit, Combined Military Hospital, Peshawar, from Jan 2013 to Dec 2014. Methodology: After approval from Hospital Ethics Committee, 38 patients diagnosed with blast lung injury who were admitted to intensive care unit were included in our study. Results: The mean age was 29.68 ± 4.3 years and all the patients were male. The incidence of blast lung injury in trauma patients was 38 (10.2%). Most of the patients 18 (47.4%) had severe ARDS due to blast wave and most of the patients 28 (73.6%) required mechanical ventilation with lung protective strategy. The mortality in patients diagnosed with blast lung injury was 2 (5.2%). Conclusion: Blast lung injury is a common complication in survivors of bomb blast. As military doctors who treat both armed forces as well civilian casualties from blast injuries; the physician treating blast injury should be conscious of risk of patient developing blast lung injury; so that early recognition and prompt management with lung protective strategy can prevent increased morbidity and mortality.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats’ lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

Use of a Shock Tube Platform in the Replication of Blast Lung Injury

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).

Author Correction: Simulation of blast lung injury induced by shock waves of five distances based on finite element modeling of a three-dimensional rat

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pulmonary injury risk curves and behavioral changes from blast overpressure exposures of varying frequency and intensity in rats

At present, there are no set guidelines establishing cumulative limits for blast exposure numbers and intensities in military personnel, in combat or training operations. The objective of the current study was to define lung injury, pathology, and associated behavioral changes from primary repeated blast lung injury under appropriate exposure conditions and combinations (i.e. blast overpressure (BOP) intensity and exposure frequency) using an advanced blast simulator. Male Sprague Dawley rats were exposed to BOP frontally and laterally at a pressure range of ~ 8.5–19 psi, for up to 30 daily exposures. The extent of lung injury was identified at 24 h following BOP by assessing the extent of surface hemorrhage/contusion, Hematoxylin and Eosin staining, and behavioral deficits with open field activity. Lung injury was mathematically modeled to define the military standard 1% lung injury threshold. Significant levels of histiocytosis and inflammation were observed in pressures ≥ 10 psi and orientation effects were observed at pressures ≥ 13 psi. Experimental data demonstrated ~ 8.5 psi is the threshold for hemorrhage/contusion, up to 30 exposures. Modeling the data predicted injury risk up to 50 exposures with intensity thresholds at 8 psi for front exposure and 6psi for side exposures, which needs to be validated further.

Gas explosion-induced acute blast lung injury assessment and biomarker identification by a LC-MS-based serum metabolomics analysis

The objective of this study was to evaluate the histopathological effect of gas explosion on rats, and to explore the metabolic alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment using metabolomics analyses. All rats were exposed to the gas explosion source at different distance points (160 m and 240 m) except the control group. Respiratory function indexes were monitored and lung tissue analysis was performed to correlate histopathological effect to serum metabolomics. Their sera samples were collected to measure the metabolic alterations by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). HE staining in lung showed that the gas explosion caused obvious inflammatory pulmonary injury, which was consistent with respiratory function monitoring results and the serum metabolomics analysis results. The metabolomics identified 9 significantly metabolites different between the control- and ABLI rats. 2-aminoadipic acid, L-methionine, L-alanine, L-lysine, L-threonine, cholic acid and L-histidine were significantly increased in the exposed groups. Citric acid and aconitic acid were significantly decreased after exposure. Pathway analyses identified 8 perturbed metabolic pathways, which provided novel potential mechanisms for the gas explosion-induced ABLI. Therefore, metabolomics analysis identified both known and unknown alterations in circulating biomarkers, adding an integral mechanistic insight into the gas explosion-induced ABLI in real roadway environment.

Damage-Associated Molecular Patterns and Their Signaling Pathways in Primary Blast Lung Injury: New Research Progress and Future Directions

Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1β, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI.