Smoke Inhalation in Veterinary Patients: Pathophysiology, Diagnosis, and Management.

Smoke contains a mixture of harmful gases, chemicals, and superheated particles. Inhalation of smoke causes generalized hypoxia and airway inflammation due to impaired oxygen transport and utilization, as well as thermal and chemical injury in the airways. Generally, treatment is supportive with oxygen therapy and airway management, including chest physiotherapy, bronchodilators, and nebulization. Immediate oxygen therapy is mandatory for all suspected smoke inhalation patients and should not be delayed pending diagnostic test results or due to "normal" oxygen saturation readings that can be falsely elevated in carbon monoxide intoxication. Smoke inhalation patients with mild clinical signs who respond well to initial stabilization generally have a favorable prognosis. However, patients with severe signs or progression despite initial stabilization may require more advanced or intensive care.

Bone marrow mesenchymal stromal cells attenuate smoke inhalation injury by regulating the M1/M2-Th17/Treg immune homeostasis axis.

Smoke inhalation injury (SII) is the leading cause of death in fire burn patients. The inflammatory response induced by smoke inhalation is a significant factor in the development of acute lung injury or acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) can alleviate various inflammatory diseases by regulating the polarization of macrophages from the M1 to the M2 phenotype. Moreover, MSCs can facilitate the inflammatory response by regulating Th17/Treg homeostasis. However, little is known about the associations among MSCs, M1/M2 macrophages and Th17/Treg homeostasis. Therefore, the purpose of this study was to evaluate whether MSCs affect subsequent Th17/Treg differentiation and immune homeostasis by regulating M1/M2 polarization in SII. Our results showed that bone marrow mesenchymal stem cells (BMSCs) ameliorated lung inflammatory injury and fibrosis after SII by affecting the polarization of alveolar macrophages (AMs) from the M1 to the M2 phenotype. Moreover, BMSCs maintain Th17/Treg immune homeostasis by increasing the proportion of Treg cells and decreasing the proportion of Th17 cells. In vitro, we further demonstrated that BMSCs promoted the polarization of AMs from the M1 to the M2 phenotype and decreased IL-23 levels. Reduced IL-23 decreased Th17 differentiation and promoted Th17/Treg balance. Therefore, BMSCs ameliorate the inflammatory response and lung damage after SII through regulating M1/M2 polarization and subsequent Th17/Treg immune homeostasis, which are linked to alveolar macrophage-derived IL-23. These findings provide novel insight into how BMSCs regulate the M1/M2-Th17/Treg immune homeostasis axis and provide new therapeutic targets for more effective control of the inflammatory response after SII.

Pediatric plastic bronchitis associated with smoke inhalation and influenza A: case report and literature review.

Plastic bronchitis is a relatively uncommon illness that has been reported in all age groups. This case report describes a specific manifestation of plastic bronchitis in two pediatric brothers influenced by both smoke inhalation and influenza A virus infection. The therapeutic approach mainly involved symptomatic supportive care, antiviral therapy, repeated bronchoscopic alveolar lavage, and bronchial cast removal. Eventually, both patients went into remission. Bronchoscopy proved to be helpful in diagnosing and treating these cases.

Protective Effects of Coenzyme Q10 on Testicular Histology in Rats Exposed via Chronic Mosquito Coil Smoke Inhalation.

OBJECTIVE: To determine the preventive effect of coenzyme Q10 (CoQ10) on the testicular histology of rats exposed chronically to mosquito coil smoke. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College/National University of Medical Sciences, Rawalpindi, Pakistan, from January to December 2020. METHODOLOGY: Thirty male Sprague Dawley rats were divided into three groups of 10 rats each. Group A was the healthy control. Group B rats were exposed to allethrin-based mosquito coil smoke for 12 weeks (4 hours/day). Group C rats received coenzyme Q10 (CoQ10, 10mg/kg/day) through oral gavage, in addition to 12 weeks of mosquito coil smoke exposure (4 hours/day). At the end of the study, testicular histology was compared among three groups including the germinal epithelium height, seminiferous tubule diameter, and testicular capsule thickness, while adjusting for the body weight variations among rats. RESULTS: The rats in Group B, exposed only to mosquito coil smoke showed testicular disruption, characterised by dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.007), as compared to the control group rats. However, the germinal epithelium height (p = 0.73) and testicular capsule thickness (p = 0.31) of rats receiving CoQ10 in addition to mosquito coil smoke inhalation were not significantly different from the control group. CONCLUSION: Prolonged inhalation of allethrin-based mosquito coil smoke can cause testicular disruption among rats. The oral CoQ10 administration can effectively prevent the histomorphological adverse effects on the testis among rats exposed to mosquito coil smoke. KEY WORDS: Allethrin, Coenzyme Q10, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule.

Hydroxocobalamin is not associated with methemoglobinemia in patients with inhalation injury and suspected cyanide toxicity and a proposed algorithm for hydroxocobalamin administration.

BACKGROUND: Cyanide poisoning poses a significant threat to burn patients exposed to smoke in residential or workplace fires, leading to central nervous system dysfunction, hemodynamic instability, cardiovascular collapse, and death. Prompt administration of an effective antidote is critical. Hydroxocobalamin, a form of vitamin B12, is the gold standard treatment for cyanide toxicity, by binding to cyanide molecules and converting them into non-toxic cyanocobalamin that is eliminated by the kidneys. This mechanism is distinct from previous cyanide antidotes, which induce the formation of methemoglobin to bind to cyanide. Recent case studies have reported elevated methemoglobin levels after hydroxocobalamin administration, raising concerns regarding its safety. The current study investigates smoke inhalation patients treated with hydroxocobalamin at a single institution Burn Unit in hopes of enhancing our understanding of the complexities surrounding cyanide antidote therapy. METHODS: After Institutional Board Approval, a retrospective cohort study was conducted. Our sample comprised burn patients with inhalation injury admitted to a single institution from 2013 to 2023 and treated with hydroxocobalamin for suspected cyanide toxicity. We also analyzed a matched control cohort of similar patients with inhalation injury not treated with hydroxocobalamin. We analyzed changes and peaks in methemoglobin levels, lactate levels, blood urea nitrogen (BUN) and creatinine, ventilator days, % total body surface area (TBSA), various types of medications and dressings, and mortality. Statistical analyses included t-tests, chi-square, linear and logistic regressions, and correlation analysis. RESULTS: In the study, 36 patients with suspected inhalation injury were treated with hydroxocobalamin at the Los Angeles General (LAG) Burn Unit from 2013 to 2023, who were matched to 32 control patients with inhalation injury who were not treated with hydroxocobalamin. Demographic and baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels. The study also revealed no significant disparities in initial lactate levels, mortality, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups. When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that hydroxocobalamin administration was not significantly associated with changes in methemoglobin or mortality. Increased %TBSA, however, was linked to elevated lactate levels. CONCLUSIONS: Our investigation sought to assess the potential risks associated with hydroxocobalamin administration in burn patients with concomitant inhalation injury. Contrary to our initial hypothesis, we found no statistically significant differences in methemoglobinemia, lactate levels, mortality, or kidney function. The influence of other factors, such as methemoglobinemia-inducing drugs or hydroxocobalamin's interference with co-oximetry, adds complexity. Although elevated methemoglobin levels were observed in some cases, their clinical significance was limited. However, this study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of hydroxocobalamin administration on burn patients' outcomes.

The impact and validity of the Berlin criteria on burn-induced ARDS: Examining mortality rates, and inhalation injury influences. A single center observational cohort study.

BACKGROUND: As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP). METHODS: Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP. RESULTS: Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a PaO2/FiO2 (PF) ratio nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001). CONCLUSIONS: The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study.

Frequency, complications, and mortality of inhalation injury in burn patients: A systematic review and meta-analysis protocol.

INTRODUCTION: Burns are tissue traumas caused by energy transfer and occur with a variable inflammatory response. The consequences of burns represent a public health problem worldwide. Inhalation injury (II) is a severity factor when associated with burn, leading to a worse prognosis. Its treatment is complex and often involves invasive mechanical ventilation (IMV). The primary purpose of this study will be to assess the evidence regarding the frequency and mortality of II in burn patients. The secondary purposes will be to assess the evidence regarding the association between IIs and respiratory complications (pneumonia, airway obstruction, acute respiratory failure, acute respiratory distress syndrome), need for IMV and complications in other organ systems, and highlight factors associated with IIs in burn patients and prognostic factors associated with acute respiratory failure, need for IMV and mortality of II in burn patients. METHODS: This is a systematic literature review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PubMed/MEDLINE, Embase, LILACS/VHL, Scopus, Web of Science, and CINAHL databases will be consulted without language restrictions and publication date. Studies presenting incomplete data and patients under 19 years of age will be excluded. Data will be synthesized through continuous (mean and standard deviation) and dichotomous (relative risk) variables and the total number of participants. The means, sample sizes, standard deviations from the mean, and relative risks will be entered into the Review Manager web analysis software (The Cochrane Collaboration). DISCUSSION: Despite the extensive experience managing IIs in burn patients, they still represent an important cause of morbidity and mortality. Diagnosis and accurate measurement of its damage are complex, and therapies are essentially based on supportive measures. Considering the challenge, their impact, and their potential severity, IIs represent a promising area for research, needing further studies to understand and contribute to its better evolution. The protocol of this review is registered on the International prospective register of systematic reviews platform of the Center for Revisions and Disclosure of the University of York, United Kingdom (https://www.crd.york.ac.uk/prospero), under number RD42022343944.

Extracorporeal Membrane Oxygenation in a Patient with Severe Inhalation Injury: Multidisciplinary Burn Team Care.

INTRODUCTION: Inhalation injury is a major risk factor for mortality in burn patients via 3 primary mechanisms: airway edema and obstruction, hypoxemic respiratory failure, and pneumonia. Currently, the mainstay of treatment is supportive care to include early intubation, lung-protective or high-frequency-percussive mechanical ventilation, nebulized heparin, and aggressive pulmonary toilet. Despite these treatments, a subset of these patients progress to severe acute respiratory distress syndrome (ARDS) for which rescue options are limited. CASE PRESENTATION: A 31-year-old woman was found down in a house fire. On admission to the burn intensive care unit, she was diagnosed with grade 3 smoke inhalation injury. Cutaneous thermal injury was absent. By hospital day 2, she developed worsening hypoxemia and hypercapnia despite maximal ventilatory support. She was placed on veno-venous extracorporeal membrane oxygenation (ECMO). She received an average of 2.2 hours of direct rehabilitation a day and completed out-of-bed modalities over 90% of total hospital days. After 159 hours, she was decannulated, and by hospital day 18, she was discharged home on supplemental oxygen. CONCLUSION: Current literature regarding ECMO in inhalation injury is limited, but a growing body of evidence suggests that treatment of severe smoke inhalation injury should include ECMO for those who fail conventional therapy.

The impact of infection on length of stay in adult burns: A scoping review.

BACKGROUND: The disruption to the immune system and profound metabolic response to burn injury gives rise to a unique susceptibility to infection. Indeed, infection is one of the most frequently encountered post-burns complications placing significant burden on patients and healthcare system. Advancements in burn care have led to marked improvements in burn-related mortality and morbidity; however, scarce hospital resources hamper adequate burn-related care, and patient length of stay (LOS) in hospital is an important drain on such resources. The aim of this review was to assess and evaluate the existing literature relating to the impact of infections on LOS in hospitalised, adult burn patients. METHODS: Electronic searches were performed in Medline and Embase. Eligible studies were those reporting on LOS and infection in adult burn populations. Articles published before 2000 were excluded to ensure that the analysis was focused on contemporary literature that reflects current, clinical management of burn patients. RESULTS: Nineteen studies (54,397 burn patients) were included in the review. All studies were retrospective, with the majority undertaken in North America (14 studies). The mean age range was 38-67 years and the majority of patients were male. Inhalation injury was recorded in eleven studies. The most common types of infection included pneumonia, blood stream infections (BSI) and burn wound infections. Overall, there was a trend towards a positive association between infection and LOS. CONCLUSION: The results of this scoping review provide an overview of the existing literature on the relationship between infection and LOS in adult burn populations. However, significant gaps remain in knowledge which call for further high-quality research. Standardised definitions for the collection of infection data and the use of burns specific infection control guidelines are also critical to understanding and improving patient outcomes.

Pediatric Polytrauma Fire Victim Simulation.

Introduction: Pediatric trauma has long been one of the primary contributors to pediatric mortality. There are multiple cases in the literature involving cyanide (CN) toxicity, carbon monoxide (CO) toxicity, and smoke inhalation with thermal injury, but none in combination with mechanical trauma. Methods: In this 45-minute simulation case, emergency medicine residents and fellows were asked to manage a pediatric patient with multiple life-threatening traumatic and metabolic concerns after being extracted from a van accident with a resulting fire. Providers were expected to identify and manage the patient's airway, burns, hemoperitoneum, and CO and CN toxicities. Results: Forty learners participated in this simulation, the majority of whom had little prior clinical experience managing the concepts highlighted in it. All agreed or strongly agreed that the case was relevant to their work. After participation, learner confidence in the ability to manage each of the learning objectives was high. One hundred percent of learners felt confident or very confident in managing CO toxicity and completing primary and secondary surveys, while 97% were similarly confident in identifying smoke inhalation injury, preparing for a difficult airway, and managing CN toxicity. Discussion: This case was a well-received teaching tool for the management of pediatric trauma and metabolic derangements related to fire injuries. While this specific case represents a rare clinical experience, it is within the scope of expected knowledge for emergency medicine providers and offers the opportunity to practice managing multisystem trauma.

Exploring the similarities and differences of burn registers globally: Results from a data dictionary comparison study.

INTRODUCTION: Pooling and comparing data from the existing global network of burn registers represents a powerful, yet untapped, opportunity to improve burn prevention and care. There have been no studies investigating whether registers are sufficiently similar to allow data comparisons. It is also not known what differences exist that could bias analyses. Understanding this information is essential prior to any future data sharing. The aim of this project was to compare the variables collected in countrywide and intercountry burn registers to understand their similarities and differences. METHODS: Register custodians were invited to participate and share their data dictionaries. Inclusion and exclusion criteria were compared to understand each register population. Descriptive statistics were calculated for the number of unique variables. Variables were classified into themes. Definition, method, timing of measurement, and response options were compared for a sample of register concepts. RESULTS: 13 burn registries participated in the study. Inclusion criteria varied between registers. Median number of variables per register was 94 (range 28 - 890), of which 24% (range 4.8 - 100%) were required to be collected. Six themes (patient information, admission details, injury, inpatient, outpatient, other) and 41 subthemes were identified. Register concepts of age and timing of injury show similarities in data collection. Intent, mechanism, inhalational injury, infection, and patient death show greater variation in measurement. CONCLUSIONS: We found some commonalities between registers and some differences. Commonalities would assist in any future efforts to pool and compare data between registers. Differences between registers could introduce selection and measurement bias, which needs to be addressed in any strategy aiming to facilitate burn register data sharing. We recommend the development of common data elements used in an international minimum data set for burn injuries, including standard definitions and methods of measurement, as the next step in achieving burn register data sharing.

Fire deaths in Cape Town, South Africa: A retrospective review of medico-legal and toxicological findings (2006 - 2018).

BACKGROUND: In South Africa, fire-related deaths are common, particularly within dense informal housing settlements. Published data on deaths from fire incidents in Cape Town is sparse. Additionally, little emphasis has been placed on the role of toxicological investigations in these deaths, despite the known risk of alcohol and drug impairment to burn injury. METHODS: A retrospective, descriptive analysis of post-mortem case reports from Salt River Mortuary was conducted to investigate all deaths in which fires were involved in the west metropole of Cape Town, between 2006 to 2018. Demographic, circumstantial, and toxicological data were analyzed using R software. RESULTS: In total 1370 fire deaths occurred over 13 years, with a mean of 106 (SD ± 18) cases per annum (≈3% of the annual caseload and a mortality rate of 5.5 per 100,000). Males (70.4%), adults (mean=30.7 years), and toddlers (1-4 years old) were notably at risk. Deaths typically occurred in the early morning (00h00 - 06h00) (45.7%), during winter (32.1%), and in lower socioeconomic areas with highly dense informal settlements (65.6%), with 29% of deaths occurring in multi-fatality incidents. Ethanol was detected (≥0.01 g/100 mL) in 55.1% of cases submitted for analysis (71.5%), with a mean of 0.18 g/100 mL, and with 93.8% of positive cases > 0.05 g/100 mL. Carboxyhaemoglobin (COHb) analysis was requested in 76.4% of cases, with 57% of cases having a %COHb of ≥ 20%. Toxicology results (for drugs other than ethanol) from the national laboratory were outstanding in 34.4% of the cases at the conclusion of the study. BAC and %COHb were significantly higher in deaths from burns and smoke inhalation (usually accidents) than deaths from combined trauma and burns (typically homicides). Fire deaths with high COHb levels were more likely to display cherry-red discoloration (OR=3.1) and soot in the airways (OR=2.7) at autopsy. CONCLUSION: This article provides an updated description of fire deaths in the west metropole of Cape Town. The importance of BAC and COHb testing in these cases was noted, and the authors call for an investigation of the role of drug impairment (specifically frequently misused drugs methamphetamine and methaqualone) as a risk factor in these deaths. Areas of high-density informal settlements, where open flames are used to heat, light, and cook, were noted as high risk.

Pathophysiologic effects of waterpipe (shisha) smoke inhalation on liver morphology and function in mice.

AIMS: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. MAIN METHODS: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. KEY FINDINGS: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinching-off of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, and IL-1ß, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1α along with alterations in the activity of mitochondrial complexes I, II, III and IV. SIGNIFICANCE: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Evaluation of hydroxocobalamin use for the treatment of suspected cyanide toxicity secondary to smoke inhalation.

Hydroxocobalamin is used for cyanide toxicity after smoke inhalation, but diagnosis is challenging. Retrospective studies have associated hydroxocobalamin with acute kidney injury (AKI). This is a retrospective analysis of patients receiving hydroxocobalamin for suspected cyanide toxicity. The primary outcome was the proportion of patients meeting predefined appropriate use criteria defined as ≥1 of the following: serum lactate ≥8 mmol/L, systolic blood pressure (SBP) <90 mmHg, new-onset seizure, cardiac arrest, or respiratory arrest. Secondary outcomes included incidence of AKI, pneumonia, resolution of initial neurologic symptoms, and in-hospital mortality. Forty-six patients were included; 35 (76%) met the primary outcome. All met appropriate use criteria due to respiratory arrest, 15 (43%) for lactate, 14 (40%) for SBP, 12 (34%) for cardiac arrest. AKI, pneumonia, and resolution of neurologic symptoms occurred in 30%, 21%, and 49% of patients, respectively. In-hospital mortality was higher in patients meeting criteria, 49% vs. 9% (95% CI 0.16, 0.64). When appropriate use criteria were modified to exclude respiratory arrest in a post-hoc analysis, differences were maintained, suggesting respiratory arrest alone is not a critical component to determine hydroxocobalamin administration. Predefined appropriate use criteria identify severely ill smoke inhalation victims and provides hydroxocobalamin treatment guidance.

iNOS inhibitor S-methylisothiourea alleviates smoke inhalation-induced acute lung injury by suppressing inflammation and macrophage infiltration.

OBJECTIVE: We investigated the effects of the inducible NO synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in a mouse model of smoke inhalation-induced acute lung injury (ALI) and explored the underlying molecular mechanism. METHODS AND ANALYSIS: A mouse model of smoke inhalation-induced ALI was established. RNA-sequencing (seq) analysis was conducted to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for functional annotation of DEGs. Moreover, an immunofluorescence assay using macrophage marker F4/80 was performed to assess macrophage infiltration. A hypoxia-induced HUVEC model was used to mimic smoke inhalation-induced injury in endothelial cells. Finally, a transwell assay was used to analyze the chemoattractive effects of endothelial cells on macrophages. RESULTS: SMT markedly alleviated the pulmonary pathological symptoms, edema, and inflammatory response in the mouse smoke inhalation-induced ALI model. RNA-seq analysis revealed that SMT may diminish lung injury by regulating the levels of genes associated with inflammatory responses, cell chemokines, and adhesion. In vivo data revealed that the protective effects of SMT against smoke inhalation-induced ALI were partly achieved by inhibiting the production of adhesion molecules and infiltration of macrophages. Furthermore, in vitro data from the hypoxia-induced HUVEC model revealed that SMT reduced macrophage chemotaxis by inhibiting the production of chemokines and adhesion molecules in endothelial cells. CONCLUSION: iNOS inhibitor SMT protects the lungs from smoke inhalation-induced ALI by reducing the production of pro-inflammatory cytokines, adhesion molecules, and chemokines in endothelial cells, thereby inhibiting inflammation and macrophage infiltration.

Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents.

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Effects of nebulized adipose-derived mesenchymal stem cells on acute lung injury following smoke inhalation in sheep.

INTRODUCTION: Treatment of ARDS caused by smoke inhalation is challenging with no specific therapies available. The aim of this study was to test the efficacy of nebulized adipose-derived mesenchymal stem cells (ASCs) in a well-characterized, clinically relevant ovine model of smoke inhalation injury. MATERIAL AND METHODS: Fourteen female Merino sheep were surgically instrumented 5-7 days prior to study. After induction of acute lung injury (ALI) by cooled cotton smoke insufflation into the lungs (under anesthesia and analgesia), sheep were placed on a mechanical ventilator for 48 hrs and monitored for cardiopulmonary hemodynamics in a conscious state. ASCs were isolated from ovine adipose tissue. Sheep were randomly allocated to two groups after smoke injury: 1) ASCs group (n = 6): 10 million ASCs were nebulized into the airway at 1 hr post-injury; and 2) Control group (n = 8): Nebulized with saline into the airways at 1 hr post-injury. ASCs were labeled with green fluorescent protein (GFP) to trace cells within the lung. ASCs viability was determined in bronchoalveolar lavage fluid (BALF). RESULTS: PaO2/FiO2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO2/PaO2) was significantly lower in the ASCs group at 36 hr (p = 0.003). Pulmonary shunt fraction tended to be lower in the ASCs group as compared to the control group. GFP-labelled ASCs were found on the surface of trachea epithelium 48 hrs after injury. The viability of ASCs in BALF was significantly lower than those exposed to the control vehicle solution. CONCLUSION: Nebulized ASCs moderately improved pulmonary function and delayed the onset of ARDS.

Circulatory HMGB1 is an early predictive and prognostic biomarker of ARDS and mortality in a swine model of polytrauma.

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72 h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6 h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.