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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., (© 2024 by American Animal Hospital Association.)

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., (© 2024. The Author(s).)

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., (Published by Oxford University Press on behalf of the American Burn Association 2024.)

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., Competing Interests: Declaration of Competing Interest This review was registered on Open Science Framework. The review protocol can be accessed through reasonable request of the authors. No funding or financial support was provided for this review. The authors declare no competing interests. Template data collection forms, data extracted from included studies, data used for all analyses and analytic code are available on reasonable request of the authors., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

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., (© 2024 Vrablik and Wing.)

Background: Burns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking., Objectives: To find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults., Methods: A randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale - VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test., Results: Baseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up., Conclusion: The reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation)., Competing Interests: Conflicts of Interest No conflict of interest., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

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: PaO 2 /FiO 2 in the ASCs group was significantly higher than in the control group (p = 0.001) at 24 hrs. Oxygenation index: (mean airway pressure × FiO 2 /PaO 2 ) 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Young, Cancio, Thorpe, Willis, Snook, Jordan, Demons, Salinas and Yang.)

Since the first burn units were established following World War II, great advances in understanding and treating burn shock, smoke inhalation injury, pneumonia, and invasive burn wound infections, and in achieving early burn-wound closure, have greatly decreased postburn morbidity and mortality. These advances were the result of closely integrated multidisciplinary teams of clinicians and researchers. The team approach to burns is a model for success in the care of any challenging clinical problem., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A systematic review of the role of extracorporeal life support (ECLS) in pediatric patients with burn and smoke inhalation injury was undertaken. A systematic search of the literature according to a specific combination of keywords to ascertain the effectiveness of this treatment strategy was conducted. A total of 14 articles out of 266 were considered suitable for the analysis in pediatric patients. The PICOS approach and PRISMA flow chart were followed for the purpose of this review. Despite the limited number of studies on the subject, ECMO in burn and smoke inhalation injury provides an additional level of support in pediatric patients leading to positive outcomes. V-V ECMO demonstrated the best overall survival of all configurations, with similar outcomes to non-burned patients. Prolonged mechanical ventilation prior to ECMO decreases survival and increases mortality by 12% with each additional day off ECMO. Good outcomes have been described for scald burns, dressing changes, and pre-ECMO cardiac arrest.

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., (© 2022. The Author(s).)

Inhalation injury is associated with high inpatient mortality, but the impact of inhalation injury after discharge and on non-mortality outcomes is poorly characterized. To address this gap, we evaluated the effect of inhalation injury on postdischarge morbidity, mortality, and hospital readmissions among patients who sustained burn injury, as well as on in-hospital outcomes for context. This was a retrospective cohort study of patients with cutaneous fire/flame burns admitted to a burn center intensive care unit from January 1, 2009 to December 31, 2015, with or without inhalation injury. Records were linked to statewide hospital admission and vital statistics databases to assess postdischarge outcomes. Mixed-effects Poisson regression was used to assess mortality, complications, and readmissions. The overall cohort included 830 patients with cutaneous burns; of these, 201 patients had inhalation injury. In-hospital mortality was 31% among inhalation injury patients vs 6% in patients without inhalation injury (adjusted OR 2.35; 95% CI 1.66-3.31). Inhalation injury was also associated with an increased risk of in-hospital pneumonia and tracheostomy (P < .05 for all). Inhalation injury was not associated with greater postdischarge mortality, all-cause readmission, readmission for pulmonary diagnosis, or readmission requiring intubation. Among the subset of patients with bronchoscopy-confirmed inhalation injury (n = 124; 62% of inhalation injuries), a higher injury grade was not associated with greater inpatient or postdischarge mortality. Inhalation injury was associated with increased early morbidity and mortality, but did not contribute to postdischarge mortality or readmission. These findings have implications for shared decision making with patients and families and for estimating healthcare utilization after initial hospitalization., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The Committee on Tactical Combat Casualty Care and Capabilities Development and Integration Directorate cite airway burn injuries as an indication for prehospital cricothyrotomy. We sought to build on previously published data by describing for the first time the incidence of prehospital airway interventions in combat casualties who received airway management in the setting of inhalational injuries.15,26 We hypothesized that (1) airway interventions in combat casualties who suffered inhalational injury would have a higher mortality rate than those without airway intervention and (2) prehospital cricothyrotomy was used with greater incidence than endotracheal intubation., Materials and Methods: Using a previously described Department of Defense Trauma Registry dataset from January 2007 to August 2016, unique casualties with documented inhalational injury were identified., Results: Our predefined search codes captured 28,222 (72.8% of all encounters in the registry) of those subjects. A total of 347 (1.2%) casualties had a documented inhalational injury, 27 (7.8%) of those with at least 1 prehospital airway intervention inhalational injuries (0.09% of our dataset [n = 28,222]). Within the subset of patients with an inhalation injury, 23 underwent intubation, 2 underwent cricothyrotomy, 3 had placement of an airway adjunct not otherwise specifically listed, and 1 casualty had both a cricothyrotomy and intubation documented. No casualties had a supraglottic, nasopharyngeal, or oropharyngeal airway listed. Contrary to our hypotheses, of those with an airway intervention, 74.0% survived to hospital discharge. In multivariable regression models, when adjusting for confounders, there was no difference in survival to discharge in those with an airway intervention compared to those without., Conclusions: Casualties undergoing airway intervention for inhalation injuries had similar survival adjusting for injury severity, supporting its role when indicated. Without case-specific data on airway status and interventions, it is challenging to determine if the low rate of cricothyrotomy in this population was a result of rapid transport to a more advanced provider capable of performing intubation or cricothyrotomy may not be meeting the needs of the medics., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Smoke inhalation results in bronchospasm of the trachea, increasing secretion of mucus, casts formation, and improvement of blood flow of the airway. High frequency chest wall oscillation is a common modality used for clearing mucus secretion in patients suffering from hypersecretion of thick mucus and used also to help cough clearance. This study aimed to detect the effect of high frequency chest wall oscillation in improving pulmonary function in burn patients suffering from smoke inhalation. Sixty smoke inhalation injury patients were randomly distributed into two groups of equal size. Group A: received high frequency chest wall oscillation and conventional chest physical therapy (breathing exercises, early ambulation, and cough training) thrice per week for 8 weeks. Group B: received traditional chest physical therapy (breathing exercises, early ambulation, and cough training) thrice per week for 8 weeks. Pulmonary function test (forced vital capacity, forced expiratory volume in the first second and peak expiratory flow rate) was measured at enrollment and after 8 weeks by using spirometer. Pulmonary function increased significantly posttreatment when compared with that pretreatment in groups A and B (P > .001). Also, they increased significantly in group A compared with that of group B posttreatment (P > .05). High-frequency chest wall oscillation have an impact on improving pulmonary function and should be handled to be a part of the pulmonary rehabilitation plan for smoke inhalation injury patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Safe administration of critical care hyperbaric medicine requires specialized equipment and advanced training. Equipment must be tested in order to evaluate function in the hyperbaric environment. High-frequency percussive ventilation (HFPV) has been used in intensive care settings effectively, but it has never been tested in a hyperbaric chamber., Methods: Following a modified U.S. Navy testing protocol used to evaluate hyperbaric ventilators, we evaluated an HFPV transport ventilator in a multiplace hyperbaric chamber at 1.0, 1.9, and 2.8 atmospheres absolute (ATA). We used a test lung with analytical software for data collection. The ventilator uses simultaneous cyclic pressure-controlled ventilation at a pulsatile flow rate (PFR)/oscillatory continuous positive airway pressure (oCPAP) ratio of 30/10 with a high-frequency oscillation percussive rate of 500 beats per minute. Inspiratory and expiratory times were maintained at two seconds throughout each breathing cycle., Results: During manned studies, the PFR/oCPAP ratios were 26/6, 22/7, and 22.5/8 at an airway resistance of 20cm H2O/L/second and 18/9, 15.2/8.5, and 13.6/7 at an airway resistance of 50 cm/H2O/L/second at 1, 1.9, and 2.8 ATA. The resulting release volumes were 800, 547, and 513 mL at airway resistance of 20 cm H2O/L/sec and 400, 253, and 180 mL at airway resistance of 50 cm/H2O/L/sec at 1, 1.9, and 2.8 ATA. Unmanned testing showed similar changes. The mean airway pressure (MAP) remained stable throughout all test conditions; theoretically, supporting adequate lung recruitment and gas exchange. A case where HFPV was used to treat a patient for CO poisoning was presented to illustrate that HFPV worked well under HBO2 conditions and no complications occurred during HBO2 treatment., Conclusion: The HFPV transport ventilator performed adequately under hyperbaric conditions and should be considered a viable option for hyperbaric critical care. This ventilator has atypical terminology and produces unique pulmonary physiology, thus requiring specialized training prior to use., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Purpose of Review: Airway management, mechanical ventilation, and treatment of systemic poisoning in burn patients with inhalation injury remains challenging. This review summarizes new concepts as well as open questions., Recent Findings: Several life-threatening complications, such as airway patency impairment and respiratory insufficiency, can arise in burn patients and require adequate and timely airway management. However, unnecessary endotracheal intubation should be avoided. Direct visual inspection via nasolaryngoscopy can guide appropriate airway management decisions. In cases of lower airway injury, bronchoscopy is recommended to remove casts and estimate the extent of the injury in intubated patients. Several mechanical ventilation strategies have been studied. An interesting modality might be high-frequency percussive ventilation. However, to date, there is no sound evidence that patients with inhalation injury should be ventilated with modes other than those applied to non-burn patients. In all burn patients exposed to enclosed fire, carbon monoxide as well as cyanide poisoning should be suspected. Carbon monoxide poisoning should be treated with an inspiratory oxygen fraction of 100%, whereas cyanide poisoning should be treated with hydroxocobalamin., Summary: Burn patients need specialized care that requires specific knowledge about airway management, mechanical ventilation, and carbon monoxide and cyanide poisoning.

Aims: To investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in smoke inhalation lung injury., Main Methods: In this study, we initially isolated exosomes from BMSCs and identified them by western blot and transmission electron microscopy. BMSC-derived exosomes were then used to treat in vitro and in vivo models of smoke inhalation lung injury. Pathologic alterations in lung tissue, the levels of inflammatory factors and apoptosis-related factors, and the expression of HMGB1 and NF-κB were determined to evaluate the therapeutic effect of BMSC-derived exosomes., Key Findings: We found that BMSC-derived exosomes could alleviate the injury caused by smoke inhalation. Smoke inhalation increased the levels of inflammatory factors and apoptosis-related factors and the expression of HMGB1 and NF-κB, and these increases were reversed by BMSC-derived exosomes. HMGB1 overexpression abrogated the exosome-induced decreases in inflammatory factors, apoptosis-related factors and NF-κB., Significance: Collectively, these results indicate that BMSC-derived exosomes can effectively alleviate smoke inhalation lung injury by inhibiting the HMGB1/NF-κB pathway, suggesting that exosome, a noncellular therapy, is a potential therapeutic strategy for inhalation lung injury., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: The use of oxygen is a key component of acute burn resuscitation, particularly when there is concern for carbon monoxide toxicity or inhalation injury. Prior studies of critically-ill patients have shown an association between early hyperoxia and increased mortality. There are no studies to date evaluating outcomes related to excessive oxygen administration in burn patients., Methods: We conducted a retrospective analysis of 219 severely burned patients to quantify the average amount of oxygen given during initial resuscitation, the level of carbon monoxide exposure, and to determine if early exposure to supratherapeutic oxygen was associated with increased hospital mortality or ventilator-associated pneumonia (VAP). The models were adjusted for inhalation injury and total body surface area (TBSA) burned., Results: Early hyperoxia in severely burn patients is common and possibly associated with increased overall mortality, although the results were inconclusive and after adjusting for burn-specific scoring systems, we found a negative correlation between hyperoxia and mortality. Confirmed carbon monoxide poisoning was relatively uncommon, but also associated with increased mortality. Patients with elevated carboxyhemoglobin did not receive more oxygen compared to others within the cohort., Conclusions: Burn patients are exposed to higher concentrations of pure oxygen compared to other critically-ill patients, presumably for empiric treatment of carbon monoxide poisoning. Our data showed a liberal use of oxygen therapy across all patients. Considering the potentially negative effects of hyperoxia, this study exposes either a gap in clinical research or need for clearer indications., (Published by Elsevier Ltd.)

Background: Grilling has become increasingly common in Germany. Although grilling is considered a non-negligible household burn hazard, few reports have assessed this type of injury. This study aimed to determine the patterns and characteristics of grill-related burn injuries and to compare these with other types of burn injuries., Methods: This retrospective observational study included all grill-related burn injuries admitted to Cologne Merheim Burn Center during 1989-2017. The collected data were analyzed descriptively and compared statistically with other fire injuries., Results: Of 1706 cases admitted with fire injuries during the study period, 160 (∼10%) involved grill-related injuries. Most cases (85%) involved men, with an average age of 34 years. Moreover, 48% and 38% of cases occurred in summer and spring, respectively. The most common mechanism of injury was ignition via fluid accelerant. The upper limb was the most commonly affected body part, followed by the head. Statistical analyses revealed that grill-related injuries were associated with a lower mean age and total body surface area, shorter in-hospital stay, and fewer complications than the other fire injury group., Conclusion: Grill-related injuries are a relatively common cause of admission to the Cologne Burn Center. Although grill-related injuries underwent a less aggressive approach than the other investigated fire injuries, the former represent a public health concern because they mainly affect the upper body, with both psychologic and aesthetic consequences. We recommend a German nationwide multi-centric study of the patterns and characteristics of burn injury., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Background: Strategies to predict delayed airway obstruction in patients with inhalation injury have not been extensively studied. This study aimed to develop a novel scale, predicting the need for Delayed Intubation after inhalation injury (PDI) score., Methods: We retrospectively identified patients with inhalation injury at four tertiary care centers in Japan between 2012 and 2018. We included patients aged 15 or older and excluded those intubated within 30 min after hospital arrival. Predictors for delayed intubation were identified with univariate analyses and scored on the basis of odds ratios. The PDI score was evaluated with the area under the receiver operating characteristic (AUROC) curve and compared with other scaling systems for burn injuries., Results: Data from 158 patients were analyzed; of these patients, 18 (11.4%) were intubated during the delayed phase. Signs of respiratory distress, facial burn, and pharyngolaryngeal swelling observed on laryngoscopy, were identified as predictors for delayed intubation. The discriminatory power of the PDI (AUROC curve = 0.90; 95% confidence interval, 0.83 to 0.97; p < 0.01) was higher than that of the other scaling systems., Conclusions: We developed a novel scale for predicting delayed intubation in inhalation injury. The score should be further validated with other population., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To introduce the experience in treating burn patients with inhalation injury during the epidemic of coronavirus disease 2019 (COVID-19). Methods: Six burn patients combined with inhalation injury were hospitalized in Department of Burns of Tongren Hospital of Wuhan University & Wuhan Third Hospital from February 1 to March 1 in 2020 during the high-incidence period of COVID-19, including 4 males and 2 females, aged 21-63 years, admitted at 2-4 hours after burns, with total burn areas of 1%-20% total body surface area (TBSA) and full-thickness burn areas of 1%-12% TBSA. Among them, 1 case had severe inhalation injury, 2 cases had mild inhalation injury, and 3 cases had moderate inhalation injury. The body temperatures of the patients were normal at the time of admission, with no fever or cough in the past 2 weeks. At admission, chest CT of one patient showed double lower lobes and left upper lobes had multiple slices and slightly high-density shadow of nodules. Chest CT of two patients showed thickening of bilateral lung texture, and the chest CT of remaining patients were normal. After admission, 6 patients were given routine treatment, the medical staffs paid attention to the protection and screened for COVID-19 according to the diagnosis and treatment plan of COVID-19. On post injury day (PID) 1, 3, 6, and 9, vein blood of patients were collected for determination of white blood cell (WBC) count, neutrophil, lymphocyte absolute value, and level of procalcitonin (PCT). Nucleic acid of novel coronavirus was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction on PID 3 and 6. The temperatures of patients were recorded after admission. The results of chest CT within one week after injury and the prognosis of the patients were recorded. Measurement data distributed normally were expressed as x ± s , and measurement data distributed abnormally were expressed as M ( P (25), P (75)). Results: (1) On PID 1, 3, 6, and 9, WBC counts of patients were respectively (19.8±3.8)×10(9)/L, (17.2±3.4)×10(9)/L, (13.3±3.1)×10(9)/L, and (11.1±1.6)×10(9)/L, neutrophils of patients were respectively 0.919±0.019, 0.899±0.011, 0.855±0.034, and 0.811±0.035, absolute values of lymphocytes of patients were respectively (0.65±0.18)×10(9)/L, (0.65±0.24)×10(9)/L, (0.91±0.34)×10(9)/L, and (1.23±0.42)×10(9)/L, and PCT values of patients were respectively 0.49 (0.36, 1.64), 0.39 (0.26, 0.73), 0.28 (0.18, 0.33), and 0.12 (0.11, 0.20) ng/mL. The values of WBC and neutrophils of patients were higher than the normal value, showing a downward trend. The absolute values of lymphocyte of patients returned to the normal value from PID 6. The PCT values of patients were higher than the normal value. (2) Nucleic acid test results of novel coronavirus of 6 patients were negative on PID 3 and 6. The temperatures of 6 patients ranged from 36.5 to 38.6 ℃. The typical imaging features of COVID-19 were not found in 6 patients within 1 week after injury by chest CT. After treatment for 14-32 days, 6 patients were cured and discharged. Conclusions: During COVID-19 pandemic, burn patients combined with inhalation injury should be treated under condition of good protection for doctors and nurses. Meanwhile, virus should be actively screened to reduce the risk of COVID-19 infection among doctors and patients.

Objective: Ventilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (V T ) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. It is uncertain whether ventilation practices changed in a similar way in burn patients. Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients., Data Sources: Systematic search of the literature in PubMed and EMBASE using MeSH, EMTREE terms and keywords referring to burn or inhalation injury and mechanical ventilation., Study Selection: Studies reporting ventilator settings in adult or pediatric burn or inhalation injury patients receiving mechanical ventilation during the ICU stay., Data Extraction: Two authors independently screened abstracts of identified studies for eligibility and performed data extraction., Data Synthesis: The search identified 35 eligible studies. V T declined from 14 ml/kg in studies performed before to around 8 ml/kg predicted body weight in studies performed after 2006. Low-PEEP levels (<10 cmH 2 O) were reported in 70% of studies, with no changes over time. Peak inspiratory pressure (PIP) values above 35 cmH 2 O were frequently reported. Nevertheless, 75% of the studies conducted in the last decade used limited maximum airway pressures (≤35 cmH 2 O) compared to 45% of studies conducted prior to 2006. Occurrence of barotrauma, reported in 45% of the studies, ranged from 0 to 29%, and was more frequent in patients ventilated with higher compared to lower airway pressures., Conclusion: This systematic review shows noticeable trends of ventilatory management in burn patients that mirrors those in critically ill non-burn patients. Variability in available ventilator data precluded us from drawing firm conclusions on the association between ventilator settings and the occurrence of VILI in burn patients., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Smoke inhalation injury is common in victims of domestic fires, among whom children are the most vulnerable. Cyanide poisoning may occur in addition to carbon monoxide poisoning and is challenging to diagnose. In France, the recommended antidotes are hydroxocobalamin for cyanide and hyperbaric oxygen for carbon monoxide. We managed a 26-month-old girl who sustained smoke inhalation injury with both carbon monoxide and cyanide poisoning during a house fire. Despite hydroxocobalamin and sodium thiosulfate therapy combined with hyperbaric oxygen, she had residual neurological impairments 3 months after the injury. The treatment challenges and detailed neurological follow-up data are described., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Aim: The literature includes few reports on the prehospital care of pediatric casualties of urban house fires. Here we aimed to describe the epidemiology of pediatric fire victims, focusing on their injuries, prehospital care, and survival., Methods: This retrospective study included children under 15 years of age who were victims of urban house fires and who received care from prehospital medical teams. The variables analyzed included epidemiology, specific care provided by prehospital emergency services, the number of cardiac arrests, and survival rates., Results: Over the 15-month study period, 365 house fires required the presence of at least one prehospital medical team. Casualties of these fires included 121 pediatric victims (median age, 4 years [interquartile range: 2-9 years]). All children were initially treated by a prehospital medical team that was not specialized in pediatrics. Six children (4.9%) received secondary treatment from a pediatric support team. Of the 121 children, 114 (94.2%) suffered from smoke inhalation and seven (5.8%) from burns. Two patients who were in cardiac arrest at their initial medical care did not survive., Conclusion: Pediatric fire casualties were initially managed by prehospital medical teams that were not specialized in pediatrics. As in adults, the main injuries were secondary to smoke inhalation, but this has increased toxicity in children. Prehospital teams not specialized in pediatrics can optimize their practice via the sharing of experiences, team training, and cognitive aid checklist for pediatric fire victims., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Smoke inhalation injury increases overall burn mortality by up to 20 times. Current therapy remains supportive with a failure to identify an optimal or targeted treatment protocol for smoke inhalation injury. The goal of this review is to describe emerging therapies that are being developed to treat the pulmonary pathology induced by smoke inhalation injury with or without concurrent burn injury., Main Body: A comprehensive literature search was performed using PubMed (1995-present) for therapies not approved by the U.S. Food and Drug Administration (FDA) for smoke inhalation injury with or without concurrent burn injury. Therapies were divided based on therapeutic strategy. Models included inhalation alone with or without concurrent burn injury. Specific animal model, mechanism of action of medication, route of administration, therapeutic benefit, safety, mortality benefit, and efficacy were reviewed. Multiple potential therapies for smoke inhalation injury with or without burn injury are currently under investigation. These include stem cell therapy, anticoagulation therapy, selectin inhibition, inflammatory pathway modulation, superoxide and peroxynitrite decomposition, selective nitric oxide synthase inhibition, hydrogen sulfide, HMG-CoA reductase inhibition, proton pump inhibition, and targeted nanotherapies. While each of these approaches shows a potential therapeutic benefit to treating inhalation injury in animal models, further research including mortality benefit is needed to ensure safety and efficacy in humans., Conclusions: Multiple novel therapies currently under active investigation to treat smoke inhalation injury show promising results. Much research remains to be conducted before these emerging therapies can be translated to the clinical arena.

Smoke inhalation resulting in acute lung injury is a common challenge facing critical care practitioners caring for patients with severe burns, contributing significantly to morbidity and mortality. The intention of this review is to critically evaluate the published literature and trends in the diagnosis, management, implications and novel therapies in caring for patients with inhalation injury.

Introduction: Patients who sustain burn injuries are frequently transferred to regional burn centers. Severely injured patients, unlikely to survive, may be transported far from home and family to die shortly after arrival. An examination of early deaths, those that happen within a week of transfer, may offer an opportunity to revise the way we think about critical burns and consider the best way to provide regional care., Methods: This is a focused review of burn patients who survived ≤1 week after transfer to a regional center from 2013-2017. Originating location data such as city, state, population at origin were obtained. Transfer data, including mode of transport and distance traveled, as well as patient characteristics, Total Body Surface Area (TBSA) burned, inhalation injury, medical history with calculation of revised-Baux (r-Baux) score were analyzed., Results: 25 patients (1.2%) met inclusion criteria. Patients were transferred from a wide geographic area with population ranges of 1000 to 279,000. 21 patients met criteria for burn resuscitation by TBSA; 4 (19%) were placed on comfort care upon arrival, 7 (33%) were placed on comfort care after discussion with the patient's family, and 10 (48%) received full resuscitation efforts. Of these 10 patients, 2 died as "full code", 8 were transitioned to comfort care after failed resuscitation or other events. Code status was not always addressed prior to the decision to transfer. Two patients were transferred after cardiac arrest in the field both of which had significant medical comorbidities in addition to their burn., Conclusions: Regional burn centers support a variety of populations. Transferring patients for which care is futile may have a profound impact on resource utilization from a variety of perspectives including transferring centers, receiving centers, regional Emergency Medical Services and families. Referring providers need to be supported in identifying these severely injured, potentially expectant patients. Transfer of patients may negatively impact families as a loved one may die far from home, before family can arrive. With our increasing ability to utilize telemedicine, transfer may not always provide the best support we can offer for providers, patients, and families., Applicability of Research to Practice: Early deaths after transfer to a regional burn center, especially those that do not undergo a full resuscitation, should be critically examined to determine the appropriateness of transfer in a palliative, patient and family centered approach., (Published by Elsevier Ltd.)

Background: Long-duration exploration missions (LDEMs), such as voyages to Mars, will present unique medical challenges for astronaut crews, including communication delays and the inability to return to Earth early. Medical events threaten crewmember lives and increase the risk of mission failure. Managing a range of potential medical events will require excellent technical and nontechnical skills (NTSs). We sought to identify medical events with potential for rescue, range them according to the potential impact on crew health and mission success during LDEMs, and develop a list of NTSs to train for management of in-flight medical events., Materials and Methods: Twenty-eight subject matter experts with specializations in surgery, medicine, trauma, spaceflight operations, NTS training, simulation, human factors, and organizational psychology completed online surveys followed by a 2-d in-person workshop. They identified and rated medical events for survivability, mission impact, and impact of crewmember NTSs on outcomes in space., Results: Sudden cardiac arrest, smoke inhalation, toxic exposure, seizure, and penetrating eye injury emerged as events with the highest potential mission impact, greatest potential for survival, and that required excellent NTS for successful management. Key NTS identified to target in training included information exchange, supporting behavior, communication delivery, and team leadership/followership., Conclusions: With a planned Mars mission on the horizon, training countermeasures need to be developed in the next 3-5 y. These results may inform policy, selection, medical system design, and training scenarios for astronauts to manage in-flight medical events on LDEMs. Findings may extend to surgical and medical care in any rural and remote location., (Copyright © 2019. Published by Elsevier Inc.)

Background: We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage., Methods: Anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, then critical care for 72h. The following groups were studied: CTR (no injury, n = 4), ICTR (injured untreated, n = 10), Allo (injured treated with allogenic MSC, n = 10), Auto (injured treated with autologous MSC, n = 10), Hemo (injured and treated with the Hemolung low flow ECLS system, n = 9), and Nova (injured and treated with the NovaLung low flow ECLS system, n = 8). Histology scores from lung, kidneys, liver, and jejunum were calculated. Data are presented as means±SEM., Results: Survival at 72h was 100% in CTR; 40% in ICTR; 50% in Allo; 90% in Auto; 33% in Hemo; 63% in Nova. ARDS developed in 0/10 CTR; 10/10 ICTR; 8/9 Hemo; 5/8 Nova; 9/10 Allo; 6/10 Auto. Diffuse alveolar damage (DAD) was present in all injured groups. MSC groups had significantly lower DAD scores than ICTR animals (Allo 26.6 ± 3.4 and Auto 18.9 ± 1.5 vs. ICTR 46.8 ± 2.1, p < 0.001). MSC groups also had lower DAD scores than ECLS animals (Allo vs. Nova, p < 0.05, Allo vs. Hemo p < 0.001, Auto vs. Nova p < 0.001, Auto vs. Hemo, p < 0.001). Kidney injury ICTR (p < 0.05) and Hemo (p < 0.01) were higher than in CTR. By logistic regression, a PaO 2 -to-FiO 2 ratio (PFR) < 300 was a function of the DAD score: logit (PFR < 300) = 0.84 + 0.072*DAD Score, odds ratio 1.074 (1.007, 1.147, p < 0.05) with a ROC AUC of 0.76, p < 0.001., Conclusion: Treatment with Auto MSC followed by Allo and then Nova were most effective in mitigating ARDS and MOF severity in this model. Further studies will elucidate the role of combination therapies of MSC and ECLS as comprehensive treatments for ARDS and MOF., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Objective: The objective of this study was to investigate the feasibility and influence of opening the lung strategy ventilation on burned patients complicated with ARDS., Methods: A prospective study was carried out in 66 moderate to severe burned patients also presented with ARDS who were randomly divided into the control group (ventilated as ARDS net) and the study group (ventilated with open lung strategy). All patients were ventilated with volume control mode until weaning., Results: Opening the lung procedure was safe in all patients with optimal PEEP of 14.8 ± 1.8 cmH 2 O. After 24 h of lung recruitment and PEEP titration, oxygenation significantly improved (PaO 2 /FiO 2 ratio increased from 119.8 ± 7.4 to 263.4 ± 11.6; p < 0.01). Along the time, the absolute values of static compliances in the study group were significantly higher (33.9 ± 0.9 vs. 26.3 ± 0.6 at 1st day; 48.4 ± 1.5 vs. 35.7 ± 0.8 at 3rd day; 48.2 ± 1.5 vs. 42.6 ± 1 at 5th day and 53.2 ± 1.8 vs. 45.3 ± 2.3 at 7th day). In addition, within the first 5 days of ventilation, PaO 2 /FiO 2 ratio significantly increased in both groups (p < 0.05) but a faster rate was recorded in the study group (176.2 ± 11.9 vs. 152.1 ± 7.5 at 1st day; 284.2 ± 16.7 vs. 210.8 ± 15.3 at 3rd day and 302.2 ± 21 vs. 233.7 ± 22.4 at 5th day, p < 0.05). Number of ventilator-free days during the first 28-days after burn injury was significantly higher in the study group (12.9 ± 5.7 vs. 9.5 ± 5.9 days; p < 0.05). Ventilation time, lengths of stay in the ICU and hospital length of stay were not significantly different across both groups (p > 0.05). In addition, duration time from ADRS onset to death and from admission to death were also remarkably longer in the study group (p < 0.05). Mortality rate was significant lower in the study group (24.2% vs. 63.6%; p < 0.01) within 7 days since onset of ARDS, but not significantly different after two weeks as well as at the 28th day after burns injury. Overall mortality rate was also not significant difference between two groups., Conclusion: It is necessary to conduct further trials to find out the effectiveness of this ventilation strategy on burns injury induced ARDS., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Objectives: Several studies have analyzed single or combinations of variables for impact on length of stay (LOS) in thermally-injured patients. The objective of this study was to evaluate a multitude of established variables and potentially identify novel variables associated with LOS in a single study., Methods: This two-year, retrospective study included all patients admitted to the burn center between January 2015 and December 2016. Exclusions included death during admission, lack of thermal or inhalation injury, age less than 18 years, readmission(s), and if pregnant or incarcerated. Baseline demographics and pertinent data were collected using electronic medical records. Regression analysis was used to determine the most predictive variables., Results: Six hundred twenty-nine patients were admitted during the inclusion period and 354 patients remained for analysis after exclusion. Univariable analysis revealed 32 variables significantly associated with LOS. Using multivariable regression, the best-fit baseline demographic model included: percent total body surface area (TBSA) injured, lower/middle socioeconomic status, clotting disorders, anemia, admission serum creatinine, and percent third degree injured (r 2  = 0.557). The best-fit combined model (incorporating baseline demographics and early in-hospital variables) included: acute kidney injury, infection and received vasopressor(s), percent TBSA injured, admission serum ethanol level, maximum C-reactive protein, and maximum total bilirubin (r 2  = 0.828)., Conclusions: There are multiple factors associated with the increased LOS seen in patients with thermal and inhalation injury. This study confirmed and identified novel factors not previously discussed in the literature that were significantly associated with LOS. Expansion of the data submitted to the National Burn Repository and the Burn Quality Improvement Program may be warranted. This study confirms claims from previous studies on inadequacy of current data submitted for benchmarking and under-reimbursement for the care of such a complex population., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To review and discuss the existing research on the pathophysiology, impact and management of inhalational injury on the larynx and lower respiratory tract., Data Sources: A literature search was conducted on the PubMed, MedLine, Embase, Web of Science and Google Scholar databases based on the keywords "airway burn", "inhalational injury" and "larynx"., Review Methods: Inclusion criteria included English language studies containing original and review data on airway injury. Data was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines., Conclusions: Abnormal laryngeal and lower airway findings are common in burns patients and the incidence tends to increase with severity of the burns. Most patients with abnormal findings remain dysphonic decades after the initial injury. Larynx, the inlet to the airway, is exposed to the most intense thermal damage and highest concentration of chemical in inhalational injury. Airway injury is common and may result in long term morbidity. Healing of this tissue architecture is prolonged and different from cutaneous burn. Many patients receive prolonged intubation for medical complications that arise due to the burn injury. The degree of subglottic damage, however, is more extensive and occurs sooner compared with those without inhalational injuries., Implications for Practice: With advances in acute medical and surgical management of burn and inhalational injury, airway injury is an important secondary outcome with lasting impact. Awareness of these potential complications and early involvement of medical and allied health team are important steps in improving patient care. A multi-disciplinary approach to management will optimise the short and long-term morbidity management and ultimately our patients' quality of life., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Smoke inhalation injury (SII) is a major morbidity and cause of mortality in patients with burns. Damage caused by inhalation of thermal or chemical irritants, including toxic fumes and chemicals, leads to respiratory cilia and epithelial cell injuries, which turn to severe bronchospasm and alveolar damage and results in acute respiratory distress syndrome. Respiratory management plays a vital role in the treatment of SII. In this review, we provide an overview of SII with emphasis on respiratory management, including aerosol therapy, bronchial hygiene therapy, advanced ventilation modes, and heated humidified high-flow nasal cannula. In summary, the information may be helpful for further improvements in outcomes., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Nebulized heparin has been proposed to improve pulmonary function in patients with inhalation injuries. The purpose of this study was to evaluate the impact of nebulized heparin with N-acetylcysteine (NAC) and albuterol on the duration of mechanical ventilation in burn patients., Methods: This is a retrospective study evaluating mechanically ventilated adult patients admitted to a regional burn center with inhalation injury. Outcomes were compared between patients who were prescribed a combination of nebulized heparin with NAC and albuterol versus similar patients who did not., Results: A total of 48 patients met inclusion criteria (heparin n = 22; nonheparin n = 26). Patients in the nonheparin group had higher percentage of total body surface area (TBSA) burned (29.00 [5.75-51.88] vs 5.25 [0.50-13.25] %TBSA; P = .009), longer duration of mechanical ventilation (6.50 [2.75-17.00] vs 3.00 [1.00-8.25] days; P = .022), and longer intensive care unit length of stay (LOS) (3.00 [3.00-28.75] vs 5.50 days [2.00-11.25]; P = .033). Upon regression, use of heparin was the only variable associated with reducing the duration of mechanical ventilation ( P = .039)., Conclusion: Nebulized heparin in combination with NAC and albuterol was associated with a significant reduction in the duration of mechanical ventilation.

To examine the protective effect of transplanting bone marrow mesenchymal stem cells (BMSCs) in treating lung injuryinduced by smoke exposure and to investigate the underlying mechanisms of this protection. SD rats were randomlydivided into four groups: normal group, normal +BMSC GFP group, smoke group, and smoke +BMSC GFP group. Todetect lung injury, we measured arterial blood gas, the wet-to-dry weight ratio, and levels of interleukin-1b, tumor necrosisfactor-a, interleukin-10, and interleukin-13 in bronchoalveolar lavage fluid and lung tissues. We also conductedhistopathology examinations. The protein markers of alveolar epithelial cells were measured to determine the BMSCdifferentiation. The protein levels of Notch1, Jagged-1, and Hes-1 also were detected. In the present study, BMSCtransplantation significantly decreased the wet-dry weight ratio of the lung, reduced the production of inflammatorymediators, and alleviated lung injury simply through differentiating into alveolar type II cells and alveolar type I cells. Western blot analysis confirmed that the protein expression of Notch-1, Jagged-1, and Hes-1 increased significantly aftersystemic BMSC transplantation. No significant difference was observed between the normal group and the nor-mal +BMSC GFP group. Our findings indicate that systemic transplantation of BMSCs alleviated lung injury induced bysmoke exposure, which may be associated with BMSCs' ability to differentiate into alveolar-type cells via the Notchsignaling pathway.

Introduction: Carbon monoxide (CO) poisoning is frequent worldwide but knowledge regarding the epidemiology is insufficient. The aim of this study was to clarify the extent of this intoxication, its mortality and factors associated with mortality., Materials and Methods: National databases from Statistics Denmark were used to identify individuals who suffered from CO-poisoning during 1995-2015, as well as information regarding co-morbidities, mortality and manner of death., Results: During the period from 1995 to 2015, 22,930 patients suffered from CO-poisoning in Denmark, and 21,138 of these patients (92%) were hospitalized. A total of 2,102 patients died within the first 30 days after poisoning (9.2%). Among these, 1,792 (85% of 2,102) were declared dead at the scene and 310 (15% of 2,102) died during hospitalization. Deaths due to CO-poisoning from smoke were intentional in 6.3% of cases, whereas deaths due to CO containing gases were intentional in 98.0% of cases. Among patients who survived >30 days, there was no significant difference in survival when comparing hyperbaric oxygen therapy (HBO) treatment with no HBO treatment after adjustment for age and co-morbidities such as drug abuse, psychiatric disease, stroke, alcohol abuse, arterial embolism, chronic obstructive pulmonary disease, cerebrovascular disease and atrial fibrillation. Several co-morbidities predicted poorer outcomes for patients who survived the initial 30 days., Conclusions: Poisoning from smoke and/or CO is a frequent incident in Denmark accounting for numerous contacts with hospitals and deaths. Both intoxication and mortality are highly associated with co-morbidities interfering with cognitive and physical function. Treatment with HBO was not seen to have an effect on survival., Competing Interests: The authors have declared that no competing interests exist.

Smoke-inhalation-induced acute lung injury (SI-ALI) is a leading cause of morbidity and mortality in victims of fire tragedies. SI-ALI contributes to an estimated 30% of burn-caused patient deaths, and recently, more attention has been paid to the specific interventions for this devastating respiratory illness. In the last decade, much progress has been made in the understanding of SI-ALI patho-mechanisms and in the development of new therapeutic strategies in both preclinical and clinical studies. This article reviews the recent progress in the treatment of SI-ALI, based on pathophysiology, thermal damage, airway obstruction, the nuclear-factor kappa-B signaling pathway, and oxidative stress. Preclinical therapeutic strategies include use of mesenchymal stem cells, hydrogen sulfide, peroxynitrite decomposition catalysts, and proton-pump inhibitors. Clinical interventions include high-frequency percussive ventilation, perfluorohexane, inhaled anticoagulants, and nebulized epinephrine. The animal model, dose, clinical application, and pharmacology of these medications are summarized. Future directions and further needs for developing innovative therapies are discussed.

Background: Tracheostomy is often performed in patients with severe burns who are undergoing prolonged mechanical ventilation. However, the appropriate timing of tracheostomy and its effect on mortality remain unknown. The aim of this study was to determine whether tracheostomy can reduce mortality in patients with severe burns., Methods: Using the Japanese Diagnosis Procedure Combination database from April 2010 to March 2014, we extracted data on adult patients with severe burns (burn index score of ≥15) who started mechanical ventilation within 3days of admission. We estimated the hazard ratio for 28-day in-hospital mortality associated with tracheotomy performed from day 5 to 28. We adjusted for baseline and time-dependent confounders using inverse probability of treatment weighting methods and fitted a marginal structural Cox proportional hazard model., Results: We identified 680 eligible patients (94 in the tracheostomy group, 2289 person-days; 586 in the non-tracheostomy group, 11,197 person-days). Patients who underwent a tracheostomy had worse prognostic factors for mortality. After adjustment for these factors, the hazard ratio for 28-day mortality associated with tracheostomy compared with non-tracheostomy was 0.73 (95% confidence interval, 0.39-1.34)., Conclusions: There was no significant association between 28-day in-hospital mortality and early tracheostomy in adult patients with severe burns., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Inhalation injury is caused by inhalation of heat, toxic or irritating gases which lead to respiratory and pulmonary parenchyma damage. At present, the clinical understanding about it is still limited and lack of effective diagnosis and treatment standard. Based on the experience of diagnosis and treatment of domestic inhalation injury, combined with reports of international researches, criteria (expert consensus) for inhalation injury were systematically discussed from pathological and pathophysiological changes, clinical diagnosis and evaluation, and clinical treatment, which provides reference for clinical diagnosis and treatment of patients inflicted with inhalation injury.

Airway edema, stenosis, obstruction and even asphyxia are easy to occur in patients with extensive burn, deep burn of head, face, and neck area, inhalation injuries, etc., which threaten life. Timely tracheotomy and intubation is an important treatment measure, but lack of knowledge and improper handling in some hospitals resulted in airway obstruction. The technique of percutaneous tracheotomy and intubation provides convenience for emergency treatment of critical burns and mass burn. The Burn and Trauma Branch of Chinese Geriatrics Society organized some experts in China to discuss the indications, timing, methods, extubation, and precautions of tracheotomy and intubation for burn patients. The national experts consensus on tracheotomy and intubation for burn patients (2018 version ) was written to provide a reference standard for clinical treatment .

Inhalation injury is caused by inhalation of heat, toxic or irritating gases which lead to respiratory and pulmonary parenchyma damage. At present, the clinical understanding about it is still limited and lack of effective diagnosis and treatment standard. Based on the experience of diagnosis and treatment of domestic inhalation injury, combined with reports of international researches, criteria (expert consensus) for inhalation injury were systematically discussed from pathological and pathophysiological changes, clinical diagnosis and evaluation, and clinical treatment, which provides reference for clinical diagnosis and treatment of patients inflicted with inhalation injury.

Introduction: Recent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit., Methods: This is a case series of consecutive patients placed on ECMO at our burn center from the initiation of our program in September 2012 to September 2017. We included only adult patients who had been placed on ECMO with burn injury, TEN, or inhalation injury and severe ARDS., Results: Fourteen patients with burn injury, inhalation injury or TEN were placed on ECMO from the initiation of the ECMO program to September 1st 2017. The average total body surface area burned in the 11 patients with burn injury was 27% (range 0.25-76%). The cause of ARDS in these patients included inhalation injury, airway trauma and bacterial pneumonia. Four patients had an inhalation injury and 1 patient had a grade 3 inhalation injury but no burn injury. In the majority of cases, prone positioning and use of neuromuscular blockade was also used in an attempt to improve oxygenation and patient synchrony with mechanical ventilation. The average time on ECMO was 276h (range 63-539h). Ten of the 14 patients survived to decanulation from ECMO (71%) and eight of 14 patients (57%) survived to hospital discharge., Conclusions: To our knowledge, this is the lowest mortality rate reported to date in burn patients with ARDS place on ECMO. ECMO is a viable therapy that can be utilized successfully as a rescue modality when conventional interventions are unsuccessful., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: Smoke inhalation injury (II) is an independent risk factor for mortality in burns and its management is inherently complex. We aim to make recommendations for best practice in managing II and its sequelae by reviewing all available current evidence in order to provide an evidence-based approach., Methods: We conducted a systematic search of the Cochrane database and Embase using PRISMA guidelines with no patient population exclusion criteria. Published work was reviewed and evidence levels graded., Results: We identified 521 abstracts for inclusion. Of the 84 articles identified for secondary review, 28 papers were excluded leaving 56 papers suitable for final inclusion., Conclusions: We are able to identify a number of strategies in both diagnosis and treatment of II that have support in the published literature, including the role of bronchoscopy, permissive hypercapnia, nebulized heparin and hydroxycobalamin. Other strategies have not been shown to be harmful, but their efficacy is also not firmly established, such as high frequency oscillatory ventilation and exogenous surfactant. Prophylactic antibiotics and corticosteroids are not recommended. In general, published evidence for II is mostly Level 3 or below, due to a noticeable lack of large-scale human studies. This represents a challenge for evidence-based burns practice as a whole., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Extracorporeal membrane oxygenation (ECMO) is one of the most frequent forms of extracorporeal life support (ECLS) and can be used as rescue therapy in patients with severe respiratory failure resulting from burns and/or smoke inhalation injury. Experience and literature on this treatment option is still very limited, consequently results are varied. We report a retrospective analysis of our experience with veno-venous (VV) ECMO in burn patients. All five patients, three male and two female (age: 28-37 years) had flame type burns and smoke inhalation injury. Their Murray scores ranged between 3.25 and 3.75, and their revised Baux scores between 62 and 102. The mean pre-ECMO conventional ventilation time was 7.4days (3-13). The mean ECMO duration was 18days (8-35). Three patients were cannulated with dual lumen, two with separate cannulae. One oxygenator had to be changed due to technical issues and two patients needed two parallel oxygenators. Four patients had renal replacement therapy. All patients needed vasoconstrictor support, antibiotics and packed red blood cells (5-62 units). Three had steroid treatment. All five patients were successfully weaned from ECMO. One patient died later from multi-organ failure in the ICU, the other four patients survived. VV-ECMO is a useful rescue intervention in patients with burns related severe respiratory failure. Patients in our institution benefit from having both burns and ECMO centres with major expertise in the field under one roof. The results from this small cohort are encouraging, although more cases are needed to draw more robust conclusions., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To systematically evaluate the effectiveness of epidermal growth factor (EGF) in treating patients with inhalation injury by meta analysis. Methods: Databases including PubMed, Cochrance Library, and Embase were searched using key words " inhalation injury, smoke inhalation injury, epidermal growth factor, and EGF" , and Chinese Journals Full-text Database, China Biology Medicine disc, VIP Database, and Wanfang Database were searched using key words in Chinese version "," to obtain the randomized controlled trails about EGF published publicly in the treatment of patients with inhalation injury from the establishment of each database to December 2017. The measurement indexes included content of total protein and albumin, colloid osmotic pressure (COP), the number of total cells, percentages of neutrophils, lymphocytes, and fibroblasts in bronchoalveolar lavage fluid (BALF), the time of disappearance of pulmonary symptoms, the time of exfoliation of necrotic mucous membrane, the time of removal of tracheal tube, the amount of respiratory secretions, and the incidence of lung infection. Meta-analysis was conducted by RevMan 5.3 statistical software. Results: A total of 6 trials involving 375 patients were included, with 182 patients in group EGF who received EGF treatment and 173 patients in conventional treatment group who received conventional treatment. All of the 6 trails had unclear risk of bias. The content of total protein and albumin and COP in BALF of patients in group EGF were lower than those in conventional treatment group, with standardized mean differences (SMDs) respectively -9.37, -26.77 , and -8.13 [with 95% confidence intervals (CIs) respectively -14.11--4.63, -41.85--11.69, -9.54--6.73, P <0.001]. The number of total cells and percentages of neutrophils and lymphocytes in BALF of patients in group EGF were lower than those in conventional treatment group, while the percentage of fibroblasts in BALF of patients in group EGF was higher than that in conventional treatment group, with SMDs respectively -20.22, -13.08, -12.28, 2.99 (with 95% CIs respectively -22.27--17.66 , -14.76--11.40, -13.86--10.70, 2.48-3.50, P <0.001). The time of disappearance of pulmonary symptoms, the time of exfoliation of necrotic mucous membrane, and the time of removal of tracheal tube of patients in group EGF were shorter than those in conventional treatment group, with SMDs respectively -1.05, -1.22 , -1.11 (with 95% CIs respectively -1.36--0.74, -1.54--0.91, -1.39--0.82, P <0.001). The amount of respiratory secretions of patients in group EGF was lower than that in conventional treatment group, with SMD -1.44 (with 95% CI -1.90--0.98, P <0.001). The incidence rate of pulmonary infection of patients in group EGF was lower than that in conventional treatment group, with relative risk 0.46 (with 95% CI 0.24-0.89, P <0.05). There may be publication bias in the content of total protein, albumin, and COP in BALF ( P <0.05), while the time of disappearance of pulmonary symptoms, the time of exfoliation of necrotic mucous membrane, and the time of removal of tracheal tube showed no significant publication bias ( P >0.05). Conclusions: Conventional treatment combined with EGF therapy can reduce respiratory inflammation of inhalation injury, promote restoration of respiratory epithelium, shorten the time of removal of tracheal tube, reduce the incidence of pulmonary infection of patients, and therefore has good effect on inhalation injury.

Objective: To investigate the effect of recombinant human keratinocyte growth factor 2 (rhKGF-2) on lung tissue of rabbits with severe smoke inhalation injury. Methods: A total of 120 New Zealand rabbits were divided into 5 groups by random number table after being inflicted with severe smoke inhalation injury, with 24 rats in each group. Rabbits in the simple injury group inhaled air, while rabbits in the injury+phosphate buffer solution (PBS) group inhaled 5 mL PBS once daily for 7 d. Rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group received aerosol inhalation of 1 mg/kg, 2 mg/kg, and 5 mg/kg rhKGF-2 (all dissolved in 5 mL PBS) once daily for 7 d, respectively. On treatment day 1, 3, 5, and 7, blood samples were taken from the ear central artery of 6 rabbits in each group. After the blood was taken, the rabbits were sacrificed, and the tracheal carina tissue and lung were collected. Blood pH value, arterial oxygen partial pressure (PaO(2)), arterial blood carbon dioxide pressure (PaCO(2)), and bicarbonate ion were detected by handheld blood analyzer. The expressions of pulmonary surfactant-associated protein A (SP-A) and vascular endothelial growth factor (VEGF) in lung tissue were detected by Western blotting. Pathomorphology of lung tissue and trachea was observed by hematoxylin-eosin staining. Data were processed with analysis of variance of two-way factorial design and Tukey test. Results: (1) Compared with those in simple injury group, the blood pH values of rabbits in the latter groups on treatment day 1-7 had no obvious change ( P >0.05). The PaO(2) of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were (75.0±2.4) and (71.0±4.5) mmHg (1 mmHg=0.133 kPa), respectively, which were significantly higher than (62.0±6.8) and (63.0±3.0) mmHg in simple injury group ( q =4.265, 8.202, P <0.05 or P <0.01). The PaO(2) of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was (82.0±4.9) mmHg, which was significantly higher than that in simple injury group ( q =6.234, P <0.01). Compared with that in simple injury group, the PaCO(2) of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 was significantly decreased ( q =4.876, P <0.01) and significantly increased on treatment day 5 ( q =5.562, P <0.01); the PaCO(2) of rabbits in injury+5 mg/kg rhKGF-2 group was significantly increased on treatment day 5 and 7 ( q =5.013, 4.601, P <0.05 or P <0.01). Compared with that in simple injury group, the serum bicarbonate ion of rabbits in injury+1 mg/kg rhKGF-2 group on treatment day 7 was significantly increased ( q =5.142, P <0.01); the serum bicarbonate ion of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were significantly increased ( q =4.830, 6.934, P <0.01); the serum bicarbonate ion of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 5 were significantly increased ( q =3.973, P <0.05). (2) The expressions of SP-A in lung tissue of rabbits in simple injury group and injury+PBS group in each treatment time point were close ( P >0.05). The expressions of SP-A in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group on treatment day 3 were 0.091±0.007 and 0.101±0.009, respectively, significantly higher than 0.069±0.009 in simple injury group ( q =10.800, 13.580, P <0.01). The expressions of SP-A in lung tissue of rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group on treatment day 5 and 7 were 0.127±0.008, 0.132±0.006, 0.194±0.006, 0.152±0.017, 0.166±0.004, 0.240±0.008, significantly higher than 0.092±0.003 and 0.108±0.005 in simple injury group ( q =6.789, 12.340, 17.900, 9.875, 31.480, 40.740, P <0.01). (3) On treatment day 1 and 5, there was no significant difference in the expression of VEGF in lung tissue of rabbits among the 5 groups ( P >0.05). Compared with those in simple injury group, the expressions of VEGF in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 and 7 were significantly increased ( q =4.243, 8.000, P <0.05 or P <0.01), and the expression of VEGF in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was significantly increased ( q =20.720, P <0.01). (4) On treatment day 1, the injury of rabbits in each group was similar, with a large number of neutrophils infiltrated and abscess formed in the alveolar and interstitial tissue, thickened alveolar septum, some collapsed alveolar and atelectasis; large area of tracheal mucosa was degenerated and necrotic, with a large amount of inflammatory exudates blocking in the cavity. On treatment day 3, the inflammation of lung tissue and trachea in each group were improved, but the inflammation in simple injury group and injury+PBS group was also serious. On treatment day 5, the inflammation in lung tissue and trachea of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group were improved much obviously than those in the other groups. On treatment day 7, the inflammation in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group alleviated obviously than those in the other groups, most alveoli had no obvious exudative fluid, the alveolar cavity was intact and clear, the local alveolar dilated like a cyst, and the alveolar septum thinning; the improvement of inflammation of trachea was more obvious than the other groups, the tracheal mucosa tended to be more complete, and few neutrophils were infiltrated in the endotracheal cavity. Conclusions: Atomization inhalation of rhKGF-2 can improve the PaO(2) level of rabbits with severe smoke inhalation injury, reduce airway inflammation, increase the expression of SP-A and VEGF in lung tissue, thus promoting the repair of lung tissue.