Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

Association of World Trade Center (WTC) Occupational Exposure Intensity with Chronic Obstructive Pulmonary Disease (COPD) and Asthma COPD Overlap (ACO).

INTRODUCTION: Reported associations between World Trade Center (WTC) occupational exposure and chronic obstructive pulmonary disease (COPD) or asthma COPD overlap (ACO) have been inconsistent. Using spirometric case definitions, we examined that association in the largest WTC occupational surveillance cohort. METHODS: We examined the relation between early arrival at the 2001 WTC disaster site (when dust and fumes exposures were most intense) and COPD and ACO in workers with at least one good quality spirometry with bronchodilator response testing between 2002 and 2019, and no physician-diagnosed COPD before 9/11/2001. COPD was defined spirometrically as fixed airflow obstruction and ACO as airflow obstruction plus an increase of ≥ 400 ml in FEV1 after bronchodilator administration. We used a nested 1:4 case-control design matching on age, sex and height using incidence density sampling. RESULTS: Of the 17,928 study participants, most were male (85.3%) and overweight or obese (84.9%). Further, 504 (2.8%) and 244 (1.4%) study participants met the COPD and ACO spirometric case definitions, respectively. In multivariable analyses adjusted for smoking, occupation, cohort entry period, high peripheral blood eosinophil count and other covariates, early arrival at the WTC site was associated with both COPD (adjusted odds ratio [ORadj] = 1.34, 95% confidence interval [CI] 1.01-1.78) and ACO (ORadj = 1.55, 95%CI 1.04-2.32). CONCLUSION: In this cohort of WTC workers, WTC exposure intensity was associated with spirometrically defined COPD and ACO. Our findings suggest that early arrival to the WTC site is a risk factor for the development of COPD or of fixed airway obstruction in workers with pre-existing asthma.

Protection of laryngeal mucosa and function in laryngeal burns by heat absorption of perilaryngeal tissue.

OBJECTIVE: The laryngeal tissue carries most of the heat during inhalation injury. This study aims to explore the heat transfer process and the severity of injury inside laryngeal tissue by horizontally studying the temperature rise process at various anatomical layers of the larynx and observing the thermal damage in various parts of the upper respiratory tract. METHODS: The 12 healthy adult beagles were randomly divided into four groups, and inhaled room temperature air (control group), dry hot air of 80 °C (group I), 160 °C (group II), and 320 °C (group III) for 20 min, respectively. The temperature changes of the glottic mucosal surface, the inner surface of the thyroid cartilage, the external surface of the thyroid cartilage, and subcutaneous tissue were measured every minute. All animals were immediately sacrificed after injury, and pathological changes in various parts of laryngeal tissue were observed and evaluated under a microscope. RESULTS: After inhaling hot air of 80 °C, 160 °C and 320 °C, the increase of laryngeal temperature in each group was ΔT = 3.57 ± 0.25 °C, 7.83 ± 0.15 °C, 11.93 ± 0.21 °C. The tissue temperature was approximately uniformly distributed, and the difference was not statistically significant. The average laryngeal temperature-time curve showed that the laryngeal tissue temperature in group I and group II showed a trend of "first decrease and then increase", except that the temperature of group III directly increased with time. The prominent pathological changes after thermal burns mainly concluded necrosis of epithelial cells, loss of the mucosal layer, atrophy of submucosal glands, vasodilatation, erythrocytes exudation, and degeneration of chondrocytes. Mild degeneration of cartilage and muscle layers was also observed in mild thermal injury. Pathological scores indicated that the pathological severity of laryngeal burns increased significantly with the increase of temperature, and all layers of laryngeal tissue were seriously damaged by 320 °C hot air. CONCLUSIONS: The high efficiency of tissue heat conduction enabled the larynx to quickly transfer heat to the laryngeal periphery, and the heat-bearing capacity of perilaryngeal tissue has a certain degree of protective effect on laryngeal mucosa and function in mild to moderate inhalation injury. The laryngeal temperature distribution was in accordance with the pathological severity, and the pathological changes of laryngeal burns provided a theoretical basis for the early clinical manifestations and treatment of inhalation injury.

Survival and analysis of prognostic factors for severe burn patients with inhalation injury: based on the respiratory SOFA score.

BACKGROUND: It is important to determine the severity of inhalation injury in severely burned patients. The oxygenation index PaO2/FiO2(PF) ratio is a key clinical indicator of inhalation injury. Sequential organ failure assessment (SOFA) is developed to assess the acute incidence of critical illness in the population. We hope to provide an assessment of survival or prognostic factor for severely burned patients with inhalation injury based on the respiratory SOFA score. METHODS: This is a retrospective cohort study of all admissions to Department of Burn and Plastic Surgery at West China Hospital of Sichuan University from July 2010 to March 2021. Data was analyzed using Cox regression models to determine significant predictors of mortality. Survival analysis with time to death event was performed using the Kaplan-Meier survival curve with the log-rank test. All potential risk factors were considered independent variables, while survival was considered the risk dependent variable. RESULTS: One hundred eighteen severe burn patients with inhalation injury who met the inclusion and exclusion criteria were admitted, including men accounted for 76.3%. The mean age and length of stay were 45.9 (14.8) years and 44.3 (38.4) days. Flame burns are the main etiology of burn (74.6%). Patients with the respiratory SOFA score greater than 2 have undergone mechanical ventilation. Univariate Kaplan-Meier analysis identified age, total body surface area burned (TBSA), ICU admission and the respiratory SOFA score as significant factors on survival. Cox regression analysis showed that TBSA and the respiratory SOFA score were associated with patient survival (p < 0.001). In some patients with severe burns and inhalation damage, the survival probability drops to less than 10% (TBSA greater than 80%: 8.9% and respiratory SOFA score greater than 2: 5.6%). This study statistically found that the TBSA with the respiratory SOFA score model (AUROC: 0.955) and the rBaux score (AUROC: 0.927) had similar predictive value (p = 0.175). CONCLUSION: The study indicates that a high respiratory system SOFA score was identified as a strong and independent predictor of severely burned patients with inhalation injury during hospitalization. When combined with TBSA, the respiratory SOFA scores can dynamically assess the severity of the patient's lung injury and improve the predictive level.

Invasive Aspergillus outbreak in inhalation injury: a case presentation and literature review.

BACKGROUND: Invasive pulmonary aspergillosis often occurs in patients with poor immune function, who abuse steroids or broad-spectrum antibiotics, or who use intravenous drugs. Among the Aspergillus genus of pulmonary infection, Aspergillus fumigatus is the most important pathogen, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Inhalation injury complicated by Aspergillus infection has atypical clinical manifestations. Diagnosis is difficult, and it is easy to make mistakes in treatment. Moreover, there are few cases of burn inhalation injury complicated with pulmonary Aspergillus. CASE PRESENTATION: We report a case of severe burns combined with severe inhalation injury, early pulmonary aspergillosis, and severe respiratory failure due to treatment discontinuation. Through analyzing the processes of diagnosis and treatment in the present case and performing a literature review, we explore feasible diagnosis and treatment plans. CONCLUSIONS: Early application of a variety of diagnostic measures can be used to identify Aspergillus infection, and targeted anti-infection treatment is likely to reverse a severe adverse prognosis.

Exercise-induced myocardial ischemia presenting as exercise intolerance after carbon monoxide intoxication and smoke inhalation Injury: case report.

BACKGROUND: Carbon monoxide intoxication and smoke inhalation injury can lead to severe disorders, and the current literature has elaborated on the importance of major cardiopulmonary impairment. Exercise intolerance has seldom been discussed, particular in patient with low cardiovascular risk. CASE PRESENTATION: Two young male fire survivors who presented with exercise intolerance after CO intoxication and smoke inhalation injury. Both received bronchodilator and glucocorticoid therapy, high-flow oxygen therapy, and hyperbaric oxygen therapy for airway edema and CO intoxication during acute care. Serum carboxyhemoglobin levels improved after treatment (8.2-3.9% in Case A and 14.8-0.8% in Case B). However, subjective exercise intolerance was noted after discharge. Cardiopulmonary exercise testing revealed exercise-induced myocardial ischemia during peak exercise (significant ST-segment depression on exercise electrocardiogram). They were instructed to exercise with precaution by setting the intensity threshold according to the ischemic threshold. Their symptoms improved, and no cardiopulmonary events were reported in the 6-month follow-up. CONCLUSION: The present case report raised the attention that exercise intolerance after carbon monoxide intoxication and smoke inhalation injury in low cardiovascular risk population may be underestimated. Cardiopulmonary exercise testing help physician to discover exercise-induced myocardial ischemia and set up the cardiac rehabilitation program accordingly.

Spectral Reflectance as a Unique Tissue Identifier in Healthy Humans and Inhalation Injury Subjects.

Tracheal intubation is the preferred method of airway management, a common emergency trauma medicine problem. Currently, methods for confirming tracheal tube placement are lacking, and we propose a novel technology, spectral reflectance, which may be incorporated into the tracheal tube for verification of placement. Previous work demonstrated a unique spectral profile in the trachea, which allowed differentiation from esophageal tissue in ex vivo swine, in vivo swine, and human cadavers. The goal of this study is to determine if spectral reflectance can differentiate between trachea and other airway tissues in living humans and whether the unique tracheal spectral profile persists in the presence of an inhalation injury. Reflectance spectra were captured using a custom fiber-optic probe from the buccal mucosa, posterior oropharynx, and trachea of healthy humans intubated for third molar extraction and from the trachea of patients admitted to a burn intensive care unit with and without inhalation injury. Using ratio comparisons, we found that the tracheal spectral profile was significantly different from buccal mucosa or posterior oropharynx, but the area under the curve values are not high enough to be used clinically. In addition, inhalation injury did not significantly alter the spectral reflectance of the trachea. Further studies are needed to determine the utility of this technology in a clinical setting and to develop an algorithm for tissue differentiation.

Inhalation Injury Grading Using Transfer Learning Based on Bronchoscopy Images and Mechanical Ventilation Period.

The abbreviated injury score (AIS) is commonly used as a grading system for inhalation injuries. While inhalation injury grades have inconsistently been shown to correlate positively with the time mechanical ventilation is needed, grading is subjective and relies heavily on the clinicians' experience and expertise. Additionally, no correlation has been shown between these patients' inhalation injury grades and outcomes. In this paper, we propose a novel inhalation injury grading method which uses deep learning algorithms in bronchoscopy images to determine the injury grade from the carbonaceous deposits, blistering, and fibrin casts in the bronchoscopy images. The proposed method adopts transfer learning and data augmentation concepts to enhance the accuracy performance to avoid overfitting. We tested our proposed model on the bronchoscopy images acquired from eighteen patients who had suffered inhalation injuries, with the degree of severity 1, 2, 3, 4, 5, or 6. As performance metrics, we consider accuracy, sensitivity, specificity, F-1 score, and precision. Experimental results show that our proposed method, with both transfer learning and data augmentation components, provides an overall 86.11% accuracy. Moreover, the experimental results also show that the performance of the proposed method outperforms the method without transfer learning or data augmentation.

Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury.

Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed.

Multiplexed Human Gene Expression Analysis Reveals a Central Role of the TLR/mTOR/PPARγ and NFkB Axes in Burn and Inhalation Injury-Induced Changes in Systemic Immunometabolism and Long-Term Patient Outcomes.

Burn patients are subject to significant acute immune and metabolic dysfunction. Concomitant inhalation injury increases mortality by 20%. In order to identify specific immune and metabolic signaling pathways in burn (B), inhalation (I), and combined burn-inhalation (BI) injury, unbiased nanoString multiplex technology was used to investigate gene expression within peripheral blood mononuclear cells (PBMCs) from burn patients, with and without inhalation injury. PBMCs were collected from 36 injured patients and 12 healthy, non-burned controls within 72 h of injury. mRNA was isolated and hybridized with probes for 1342 genes related to general immunology and cellular metabolism. From these specific gene patterns, specific cellular perturbations and signaling pathways were inferred using robust bioinformatic tools. In both B and BI injuries, elements of mTOR, PPARγ, TLR, and NF-kB signaling pathways were significantly altered within PBMC after injury compared to PBMC from the healthy control group. Using linear regression modeling, (1) DEPTOR, LAMTOR5, PPARγ, and RPTOR significantly correlated with patient BMI; (2) RPTOR significantly correlated with patient length of stay, and (3) MRC1 significantly correlated with the eventual risk of patient mortality. Identification of mediators of this immunometabolic response that can act as biomarkers and/or therapeutic targets could ultimately aid the management of burn patients.

Assessment and clinical management of internal contamination.

Internal contamination by radionuclides may occur through inhalation, ingestion and absorption through the skin or subcutaneous tissue. The clinical management of internalized radionuclides requires the integration of clinical signs and symptoms with dose estimates in biological tissues obtained from the face, nose, sputum, urine, faeces and/or skin. The assessment of ingested radionuclides includes bioassays of urine and faeces, and if available, whole body counting for radionuclides that emit penetrating x-rays or gamma-rays. An estimate of intake dose may be made at the time of initial patient evaluation by measuring radioactivity, converting counts/minute to depositions/minute with a specific gamma-ray constant, and comparing the amount to its annual limit on intake, clinical decision guide or derived reference level. Since nobody dies from internal contamination per se, medically unstable patients should be stabilized before addressing internal contamination. Whenever possible, internal contaminants should be physically removed as soon as possible after exposure. For inhaled internal contaminants, radionuclide-specific therapy may include the administration of an ion exchange resin (i.e. Prussian blue, PB) or chelating agent (i.e. diethylenetriamine pentaacetate, DTPA, that binds toradioactiveplutonium, americium, and curium), or the physical removal of insoluble particles with a high activity radionuclide (192Ir,90Sr,210Po) by bronchioalveolar lavage. Decorporation with PB, DTPA and other agents is used to enhance excretion. The treatment of wounds contaminated with an actinide includes gentle irrigation, surgical excision of contaminated tissue and DTPA. The averted dose (i.e. the total effective dose averted by therapy) may be calculated for each exposure route.

A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. METHODS: Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. RESULTS: Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. CONCLUSIONS: This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

Serious Inhalation Injuries From Military Operations in Afghanistan, Iraq, and Syria.

OBJECTIVE: To characterize serious inhalation injuries seen during recent military operations, and assess whether bronchoscopic severity findings were associated with clinical presentation and outcomes. METHODS: Service members who suffered inhalation injuries while deployed to Iraq, Afghanistan, or Syria from 2001-2018 were identified using ICD-9 and 10 codes from the Expeditionary Medical Encounter Database (EMED), which is abstracted from patient records in forward-deployed medical facilities. Further information including demographics, mechanism of injury, mortality, total burn surface area (TBSA), degree of facial burn, total Injury Severity Score (ISS), and first post-injury bronchoscopy notes were collected. Patients were excluded with ISS less than 16 or without sufficient details regarding bronchoscopy. Injuries were grouped based on bronchoscopic Abbreviated Injury Scores (AIS) into low-grade (AIS of 1), moderate-grade (AIS of 2), or high-grade (AIS of 3 or 4). RESULTS: 91 patients met inclusion criteria, with no significant differences in age, gender, paygrade, or service branch between degrees of injury. There were no statistical correlations between grade of injury and battle versus non-battle injury, blast versus non-blast mechanism, TBSA, or degree of facial burn. High-grade injuries had significantly higher ISS than low or moderate-grade injuries. After adjusting for ISS, the odds ratio of death was 10.4 (95% CI 1.47 to 74.53) for those with high-grade and 3.7 (95% CI 0.45 to 32.30) for those with moderate-grade compared to low-grade injuries. CONCLUSION: In this cohort of deployed military members with inhalation injuries, initial bronchoscopic severity findings are strongly associated with mortality even after adjusting for ISS. The AIS may be an important prognostic tool in all of those with serious inhalation injuries.

Modified abbreviated burn severity index as a predictor of in-hospital mortality in patients with inhalation injury: development and validation using independent cohorts.

PURPOSE: The ability to accurately evaluate the severity of inhalation injury can help to optimize patient care. However, there is no accepted severity grading system, especially for inhalation injury. METHODS: We screened a multicenter burn registry and included adult patients who required oxygen treatment or mechanical ventilation. After the patient data were divided into development and validation cohorts, missing values were replaced with multiple imputation. Twelve potential predictors were analyzed using multivariate logistic regression to identify prognostic variables for in-hospital mortality and scores were assigned to each predictor based on odds ratios to develop the Modified Abbreviated Burn Severity Index, mABSI. The mABSI was validated using c-statistics and calibration curves. RESULTS: We randomly assigned 1377 and 919 patients to the development and validation cohorts, respectively. Age, self-inflicted injury, cutaneous burn area, and mechanical ventilation requirement were identified as independent predictors, and the mABSI (1-17 scale) was, thus, developed. The mABSI has a high discriminatory power (c-statistic = 0.94; 95% CI 0.92-0.97), and both estimated and observed in-hospital mortalities increased from 1% at score ≤ 5 to almost 100% at score ≥ 14 with linear calibration plots. CONCLUSIONS: We developed and validated the mABSI which accurately predicts in-hospital mortality.

Cyanide poisoning in patients with inhalation injury - the phantom menace.

Inhalation injury is a serious complication in patients with burns that dramatically increases their morbidity and mortality. These patients are always suspected of having inhalation injury with potential intoxication. We usually encounter carbon monoxide intoxication, but it is necessary to think about the possibility of poisoning by other combustion products. Cyanide intoxications are less common, but their diagnosis and treatment are more complicated. The diagnosis can only be based on the history, clinical findings, and indirect laboratory signs. Direct determination of plasma cyanide levels is not generally adopted in routine clinical practice. Nowadays, several specific antidotes with different mechanisms of action are available. There are no clear guidelines on the antidote of choice, as the evidence base is limited by a lack of randomised controlled trials in humans. In two mini case reports, we present our experience with the diagnosis and therapy of patients with suspected cyanide poisoning.

The History of Carbon Monoxide Intoxication.

Intoxication with carbon monoxide in organisms needing oxygen has probably existed on Earth as long as fire and its smoke. What was observed in antiquity and the Middle Ages, and usually ended fatally, was first successfully treated in the last century. Since then, diagnostics and treatments have undergone exciting developments, in particular specific treatments such as hyperbaric oxygen therapy. In this review, different historic aspects of the etiology, diagnosis and treatment of carbon monoxide intoxication are described and discussed.

A comparative study of a preclinical survival model of smoke inhalation injury in mice and rats.

Smoke inhalation injury increases morbidity and mortality. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. The goal of our research was threefold: 1) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous mouse model, 2) to validate the rat smoke inhalation injury model using a variety of laboratory techniques, and 3) to compare and contrast our rat model with both the well-established mouse model and previously published rat models to highlight our improvements on smoke delivery and lung injury. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. Lung sections were hematoxylin and eosin stained, lung edema was assessed with wet-to-dry (W/D) ratio, and inflammatory cell infiltration and cytokine elevation were evaluated using flow cytometry, immunohistochemistry, and ELISA. We confirmed that our mouse and rat models of smoke inhalation injury mimic the injury seen after human burn inhalation injury with evidence of pulmonary edema, neutrophil infiltration, and inflammatory cytokine elevation. Interestingly, rats mounted a more severe immunological response compared with mice. In summary, we successfully validated a reliable and clinically translatable survival model of lung injury and immune response in rats and mice and characterized the extent of this injury. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic.

Blood carboxyhemoglobin elimination curve, half-lifetime, and arterial-venous differences in acute phase of carbon monoxide poisoning in ovine smoke inhalation injury model.

Smoke inhalation injury (SII) affects more than 50,000 people annually causing carbon monoxide (CO) poisoning. Although the increased blood level of carboxyhemoglobin (CO-Hb) is frequently used to confirm the diagnosis of SII, knowledge of its elimination in the acute phase is still limited. The aim of this study is to determine CO-Hb elimination rates and their differences in arterial (aCO-Hb) and mixed-venous (vCO-Hb) blood following severe SII in a clinically relevant ovine model. Forty-three chronically instrumented female sheep were subjected to SII (12 breaths, 4 sets) through tracheostomy tube under anesthesia and analgesia. After the SII, sheep were awakened and placed on a mechanical ventilator (FiO2 = 1.0, tidal volume 12 mL/kg, and PEEP = 5cmH2O) and monitored. Arterial and mixed-venous blood samples were withdrawn simultaneously for blood gas analysis at various time points to determine CO-HB half-lifetime and an elimination curve. The mean of highest aCO-Hb level during SII was 70.8 ± 13.9%. The aCO-Hb elimination curve showed an approximated exponential decay during the first 60 min. Per mixed linear regression model analysis, aCO-Hb significantly (p < 0.001) declined (4.3%/minute) with a decay constant lambda of 0.044. With this lambda, mean lifetime and half-lifetime of aCO-Hb were 22.7 and 15.7 min, respectively. The aCO-Hb was significantly lower compared to vCO-Hb at all-time points (0-180 min). To our knowledge, this is the first report describing CO-Hb elimination curve in the acute phase after severe SII in the clinically relevant ovine model. Our data shows that CO-Hb is decreasing in linear manner with supportive mechanical ventilation (0-60 min). The results may help to understand CO-Hb elimination curve in the acute phase and improvement of pre-hospital and initial clinical care in patients with CO poisoning.