Effects of bone marrow-derived mesenchymal stemcells engraftment on vascular endothelial cell growthfactor in lung tissue and plasma at early stage of smoke inhalation injury

BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.

Effects of early bronchoalveolar lavage fluid collected from dogs with smoke inhalation injury on the lungs of rats

Objective: Whether early massive bronchoalveolar lavage can remove the harmful substances from the lungs injured with smoke inhalation remains uncertain. This study was designed to observe the effects of early massive bronchoalveolar lavage fluid (BALF) on the healthy lungs in rats. Methods: Mongrel dogs were inflicted with severe smoke inhalation injury. The injured lungs were lavaged with large amount of normal saline in the first hour after injury and the BALF was collected. The BALF was injected into the healthy lungs of 30 rats (group C) in the dosage of 5 ml/kg. The functions and pathological changes of the lungs were observed 24 h after perfusion with the BALF. The data were compared with those of 23 rats (group B) whose lungs were perfused with the BALF collected from normal dogs and those of 21 rats (group A) whose lungs were perfused with normal saline. Results: The mortality rate 24 h after lung perfusion was higher in group C than in groups A and B. The survivors of group C exhibited fluctuation of respiratory rate (RR), remarkable decrease of PaO 2, significantly higher content of lung water, decrease of total static pulmonary compliance and pulmonary expansion index, and increasse of inflammatory cytokines in the tissues of lungs. Only slight mechanic obstructive effect on the airway was observed in rats of group A and B. The pathological changes of the lungs of the rats in group C were similar to those of the dogs with actual smoke inhalation injury. Conclusion: Our findings indicate that the BALF collected from dogs with acute severe smoke inhalation injury in the early stage after injury injured the normal lungs of rats with the bioactive substances in the BALF. These findings show us that it is a valuable therapeutic procedure to apply massive bronchoalveolar fluid lavage in the early stage after inhalation injury.

The Protective Effects of Preventive Atomisation Inhalation of Edaravone on the Lung Tissues of Rats with Smoke Inhalation Injury

Objective: To investigate the protective effects of the atomisation inhalation of edaravone on the lung tissues of rats with smoke inhalation injury. Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups of ten rats each: normal control group (group A), normal saline atomisation group (group B), edaravone aerosol group (group C) and edaravone atomisation prevention group (group D). Barring group A, the groups were used to create a model of severe smoke inhalation injury. However, before developing the model, group D rats were made to inhale edaravone (3.6 mg/mL) for 10 min. Six hours following smoke inhalation injury, abdominal artery blood samples were centrifuged, the lung tissue homogenate was prepared and carotid artery blood samples were used for blood gas analysis and oxygenation index (PaO2/FiO2) calculation. The levels of tumour necrosis factor alpha (TNF-α), interleukin (IL) 6 and IL-10 in serum and the levels of cysteine protease 3 (caspase-3), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD) in lung tissues were examined. The wet-dry ratio (W/D) and water content of the lung tissue were calculated, and the TUNEL method was used to determine the rate of lung tissue apoptosis in each group. Tissue specimens were obtained from the partial lung for histopathological examination. Results: Compared with those in group A, the water content of the lung tissue, the rate of lung tissue apoptosis, W/D and the caspase-3, TNF-α, IL-6, IL-10, MDA and MPO levels were significantly greater in other groups (PP< 0.05). Compared with those in group B, the levels of W/D, the water content of the lung tissue, the rate of lung tissue apoptosis and the levels of caspase-3, TNF-α, IL-6, MDA and MPO were significantly low (P and the levels of IL-10, SOD and PaO2/FiO2 were significantly high in groups C and D (P The expression of the aforementioned factors was more evident in Group D (P < 0.05). Histopathological examination revealed that groups C and D had greater levels of inflammatory granulocytes than group B. This was more evident in group D. Conclusions: The inhalation of edaravone can reduce smoke inhalation-induced lung injury. This may be related to the inhibition of apoptosis, the reduction of peroxidation injury and the production/release of inflammatory mediators/free radicals. It exerts a remarkable preventive effect.

Nebulized heparin for inhalation injury in burn patients:a systematic review and meta-analysis

Background:Smoke inhalation injury increases overall burn mortality.Locally applied heparin attenuates lung injury in burn animal models of smoke inhalation.It is uncertain whether local treatment of heparin is benefit for burn patients with inhalation trauma.We systematically reviewed published clinical trial data to evaluate the effectiveness of nebulized heparin in treating burn patients with inhalation injury.Methods:A systematic search was undertaken in PubMed,the Cochrane Library,Embase,Web of Science,the Chinese Journals Full-text Database,the China Biomedical Literature Database and the Wanfang Database to obtain clinical controlled trails evaluating nebulized heparin in the treatment of burn patients with inhalation injury.Patient and clinical characteristics,interventions and physiological and clinical outcomes were recorded.Cochrane Risk of Bias Evaluation Tool and the Newcastle–Ottawa Scale were used to evaluate data quality.Potential publication bias was assessed by Egger’s test.A sensitivity analysis was conducted to assess the stability of the results.The meta-analysis was conducted in R 3.5.1 software.Results:Nine trials were eligible for the systematic review and meta-analysis.Nebulized heparin can reduce lung injury and improve lung function in burn patients with inhalation injury without abnormal coagulation or bleeding,but the findings are still controversial.Mortality in the heparintreated group was lower than that of the traditional treatment group(relative risk(RR)0.75).The duration of mechanical ventilation(DOMV)was shorter in the heparin-treated group compared to the traditional treatment group(standardized mean difference(SMD)−0.78).Length of hospital stay was significantly shorter than that in the traditional treatment group(SMD−0.42),but incidence rates of pneumonia and unplanned reintubation were not significantly different in the study groups(RRs 0.97 and 0.88,respectively).No statistically significant publication biases were detected for the above clinical endpoints(p>0.05).Conclusions:Based on conventional aerosol therapy,heparin nebulization can further reduce lung injury,improve lung function,shorten DOMV and length of hospital stay,and reduce mortality,although it does not reduce the incidence of pneumonia and/or the unplanned reintubation rate.

Treatment of severe burn injury of 98%TBSA with 95% full-thickness burn and severe inhalation injury:a case report

The treatment of extensive severe burn injury is very difficult, especially when some complications are involved. A burned patient sustained 98% total body surface area (TBSA) with 95% full thickness burn and severe inhalation injury was admitted to our hospital in 08- 2000. After aggressive treatment, the patient recovered fully. This paper reports the treatment of the patient.

Effects of Cigarette Smoke Extract on E-cadherin Expression in Cultured Airway Epithelial Cells

Summary: To investigate whether the change of E-cadherin (ECD) expression plays a role in the injury and repair of airway epithelial cells (AEC) caused by smoking, porcine AECs were cultured by using an enzyme-dispersed method. After exposure of the AECs to cigarette smoke extract (CSE), the ECD expression in the cells was detected by using immunocytochemistry and in situ hybridization. The results showed that ECD was distributed on the plasma membrane at the cell junctions of AECs. After exposure to 20 % CSE, the membranous ECD expression was decreased, the cytoplasmic ECD expression was increased (P<0.01) as the exposure time went on. But the content of ECD mRNA in the AECs did not chang. It suggests that the change of ECD ex- pression is regulated at the posttranslational level and plays a role in the injury and repair of AEC caused by smoking.

Serum zinc level is associated with liver dysfunction caused by white smoke inhalation

Background:White smoke bomb exposure in the military setting could result in organ injuries,which is uncommon and has been rarely described in previous studies.The aim of this study is to observe whether serum zinc levels are associated with liver function after white smoke inhalation.Methods:Fifteen patients with white smoke exposure were the subjects in this study.The clinical manifestations,liver function tests and the serum zinc levels were analysed.Results:The level of serum zinc was increased in the moderate or severe group(n=4)compared with that in the mild group(n=11).The four cases in the moderate or severe group had delayed impairment of liver function with an elevation of alanine transaminase.Additionally,increased blood concentrations of hyaluronic acid were found in three patients in the moderate or severe group.But no hexachloroethane or trichloropropane was detected.Conclusion:This study suggested that serum zinc levels may be associated with the severity of liver injuries after white smoke inhalation.

Survival analysis and mortality predictors of hospitalized severe burn victims in a Malaysian burns intensive care unit

Background:Prognostic measures to determine burn mortality are essential in evaluating the severity of individual burn victims.This is an important process of triaging patients with high risk of mortality that may be nursed in the acute care setting.Malaysian burn research is lacking with only one publication identified which describes the epidemiology of burn victims.Therefore,the objective of this study was to go one step further and identify the predictors of burn mortality from a Malaysian burns intensive care unit(BICU)which may be used to triage patients at higher risk of death.Methods:This is a retrospective cohort study of all admissions to Hospital Sultan Ismail’s BICU from January 2010 till October 2015.Admission criteria were in accordance with the American Burn Association guidelines,and risk factors of interest were recorded.Data was analyzed using simple logistic regression to determine significant predictors of mortality.Survival analysis with time to death event was performed using the Kaplan-Meier survival curve with log-rank test.Results:Through the 6-year period,393 patients were admitted with a male preponderance of 73.8%.The mean age and length of stay were 35.6(±15.72)years and 15.3(±18.91)days.There were 48 mortalities with an overall mortality rate of 12.2%.Significant risk factors identified on simple logistic regression were total body surface area(TBSA)>20%(p<0.001),inhalation injury(p<0.001)and presence of early systemic inflammatory response syndrome(SIRS)(p<0.001).Survival analysis using Kaplan-Meier survival curve showed similar results with TBSA>20%,presence of SIRS,mechanical ventilation and inhalation injury which were associated with poorer survival(p<0.001).Conclusion:The predictors of mortality identified in a Malaysian BICU were TBSA>20%,early SIRS,mechanical ventilation and inhalation injury which were associated with poorer survival outcome.The immunological response differs from individual patients and influenced by the severity of burn injury.Early SIRS on admission is an important predictor of death and may represent the severity of burn injury.Patients who required mechanical ventilation were associated with mortality and it is likely related to the severity of pulmonary insults sustained by individual patients.This data is important for outcome prognostication and mortality risk counselling in severely burned patients.

Extracorporeal membrane oxygenation for acute respiratory distress syndrome in burn patients:a case series and literature update

Background:Acute respiratory distress syndrome(ARDS)has a reported incidence of 34–43%in ventilated burn patients and is associated with a mortality of 59%in the severe form.The use and experience with extracorporeal membrane oxygenation(ECMO)in burn patients developing ARDS are still limited.We present our results and discuss the significance of ECMO in treating burn patients.Methods:A retrospective analysis of burn patients treated with ECMO for ARDS between January 2017 and January 2019 was performed.Demographic,clinical,and outcome data were collected and analyzed.Results:Eight burn patients were treated at our institution with ECMO in the designated time period.Of these,all but one patient had inhalation injury,burn percentage of TBSA was 37±23%,ABSI score was 8.4±2,and R-Bauxscore was 98±21.Seven patients developed severe ARDS and one patient moderate ARDS according to the Berlin classification with a PaO_(2)/FiO_(2) ratio upon initiation of ECMO therapy of 62±22 mmHg.ECMO duration was 388±283 h.Three patients died from severe sepsis while five patients survived to hospital discharge.Conclusions:ECMO is a viable therapy option in burn patients developing severe ARDS and can contribute to survival rates similar to ECMO therapy in non-burn-associated severe ARDS.Consequently,patients with severe respiratory insufficiency with unsuccessful conventional treatment and suspected worsening should be transferred to burn units with the possibility of ECMO treatment to improve outcome.

Interpretation for practice guidelines for prevention, diagnosis, and treatment of ventilator-associated pneumonia in burn patients by american burn association

"American Burn Association Practice Guidelines for Prevention,Diagnosis,and Treatment of Ventilator-Associated Pneumonia in Burn Patients"was published to provide recommendation for the prevention,diagnosis,and treatment of ventilator-associated pneumonia in burn patients.This article makes interpretations and conclusions for prevention,diagnosis and treatment from this guideline in the combination of domestic burn patients.

Unplanned decannulation of tracheotomy tube in massive burn patients： a retrospective case series study

Background Unplanned extubation is associated with adverse outcomes in intensive care unit. The massive burn patient differs from other critically ill patients in many ways. However, little is known about the unplanned decannulation （UD） in Burn Intensive Care Unit. This paper describes the special features of the circumstances and outcome of UD of tracheotomy tube in massive burn patients. Methods A case series study was performed between January 1999 and December 2008 and UD of tracheotomy tube was analyzed retrospectively. A total of 21 patients with 29 UD events were identified. Demographic data, diagnosis, intervention, UD events and outcome of UD patients were collected. Differences in proportions were compared using the chi-square （X2） or Fisher＇s exact test. Results Patients with UD were often burned with head and neck （67%） and combined with inhalation injury （62%）. The majority of them （76%） were transferred patients, occurred early （55%） and were accidental UD （79%）. UD events tended to happen in day shift （90%） and to be associated with the medical procedure that was performing by caregivers at besides （79%）. Loose of the stabilizing rope, medical procedure and tracheotomy malposition were the main causes of UD. Early UD and reintubation failure were associated with patients＇ death. Conclusions UD happened to massive burn patients can lead to patient death. Careful management of respiratory tract was essential for massive burn patients.

Influence of moxa smoke on mitochondrial transmembrane potential and Bax/Bcl-2 in alveolar type Ⅱ epithelial A549 cells

Objective： To investigate the influence of moxibustion products on mitochondrial transmembrane potential （MTP） and mRNA expression of Bax/Bcl-2 in alveolar type Ⅱ epithelial A549 cells, and to further explore influence of moxibustion products on the oxidative damage of A549 cells. Methods： Smoke and particles generated by moxibustion were collected using the filter box for gas sampling. The moxa smoke extract （MSE） was diluted sequentially to the final concentrations of 0.05 mg/mL, 0.2 mg/mL, 0.2 mg/mL, 0.3 mg/mL and 0.4 mg/mL using the cell culture medium, and A549 cells were then intervened by the above MSE solution. Cell MTP was detected by JC-1 staining. Fluorescence quantitative polymerase chain reaction （PCR） was used to detect Bax/Bcl-2 mRNA expression of A549 cells. Results： Compared with cells in the normal control group, MTP was significantly decreased in cells of 0.3 mg/mL and 0.4 mg/mL MSE intervention groups （P〈0.01）; while MTP showed no significant changes in cells of 0.05 mg/mL, 0.1 mg/mL and 0.2 mg/mL MSE intervention groups （P〉0.05）; compared with cells in 0.05 mg/mL MSE intervention group, MTP was decreased significantly in cells of 0.1 mg/mL, 0.2 mg/mL, 0.3 mg/mL and 0.4 mg/mL MSE intervention groups （P〈0.05）; compared with cells in 0.1 mg/mL MSE intervention group, MTP was decreased significantly in cells of 0.4 mg/mL MSE intervention group （P〈0.01）. Bax mRNA expression of cells in each concentration of MSE intervention group all showed no significant difference compared to that in the normal control group; Bcl-2 mRNA expression of cells was reduced with the increase of MSE intervention concentration. Wherein, Bcl-2 mRNA expressions of cells in 0.4 mg/mL and 0.3 mg/mL MSE intervention groups were significantly reduced compared with that of cells in the normal control group （P〈0.05）; Bcl-2 mRNA expression of cells in 0.4 mg/mL MSE intervention group was significantly reduced compared to that in 0.05 mg/mL MSE intervention group （P〈0.05）. Conclusion： Certain higher concentration of moxa smoke could reduce MTP and mRNA expression of the anti-apoptosis gene Bcl-2 in alveolar type Ⅱ epithelial A549 cells. Oxidative damage may be the important mechanism of apoptosis caused by the high concentration of moxa smoke solution, and further studies are necessary on the specific mechanisms.

Ventilation strategies in burn intensive care:A retrospective observational study

Consensus regarding optimal burns intensive care(BICU)patient management is lacking.This study aimed to assess whether ventilation strategies,cardiovascular support and sedation in BICU patients have changed over time,and whether this affects outcome.A retrospective observational study comparing two 12-patient BICU cohorts(2005/06 and 2010/11)was undertaken.Demographic and admission characteristics,ventilation parameters,sedation,fluid resuscitation,cardiovascular support and outcome(length of stay,mortality)data were collected from patient notes.Data was analysed using T-tests,Fisher’s exact and Mann-Whitney U tests.In our study cohort groups were equivalent in demographic and admission parameters.There were equal ventilator-free days in the two cohorts 10±12.7 vs.13.3±12.2 ventilator free days;(P=0.447).The 2005/06 cohort were mechanically ventilated more often than in 2010/11 cohort(568 ventilator days/1000 patient BICU days vs.206 ventilator days/1000 patient BICU days;P=0.001).The 2005/06 cohort were ventilated less commonly in tracheostomy group/endotracheal tube spontaneous(17.8%vs.26%;P=0.001)and volumecontrolled modes(34.4%vs.40.8%;P=0.001).Patients in 2010/11 cohort were more heavily sedated(P=0.001)with more long-acting sedative drug use(P=0.001)than the 2005/06 cohort,fluid administration was equivalent.Patient outcome did not vary.Inhalational injury patients were ventilated in volume-controlled(44.5%vs.28.1%;P=0.001)and pressure-controlled modes(18.2%vs.9.5%;P=0.001)more frequently than those without.Outcome did not vary.This study showed there has been shift away from mechanical ventilation,with increased use of tracheostomy/tracheal tube airway spontaneous ventilation.Inhalation injury patients require more ventilatory support though patient outcomes do not differ.Prospective trials are required to establish which strategies confer benefit.

Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis

Background:Respiratory and circulatory dysfunction are common complications and the leading causes of death among burn patients,especially in severe burns and inhalation injury.Recently,extracorporeal membrane oxygenation(ECMO)has been increasingly applied in burn patients.However,current clinical evidence is weak and conflicting.This study aimed to comprehensively evaluate the efficacy and safety of ECMO in burn patients.Methods:A comprehensive search of PubMed,Web of Science and Embase from inception to 18 March 2022 was performed to identify clinical studies on ECMO in burn patients.The main outcome was in-hospital mortality.Secondary outcomes included successful weaning from ECMO and complications associated with ECMO.Meta-analysis,meta-regression and subgroup analyses were conducted to pool the clinical efficacy and identify influencing factors.Results:Fifteen retrospective studies with 318 patients were finally included,without any control groups.The commonest indication for ECMO was severe acute respiratory distress syndrome(42.1%).Veno-venous ECMO was the commonest mode(75.29%).Pooled in-hospital mortality was 49%[95%confidence interval(CI)41-58%]in the total population,55%in adults and 35%in pediatrics.Meta-regression and subgroup analysis found that mortality significantly increased with inhalation injury but decreased with ECMO duration.For studies with percentage inhalation injury≥50%,pooled mortality(55%,95%CI 40-70%)was higher than in studies with percentage inhalation injury<50%(32%,95%CI 18-46%).For studies with ECMO duration≥10 days,pooled mortality(31%,95%CI 20-43%)was lower than in studies with ECMO duration<10 days(61%,95%CI 46-76%).In minor and major burns,pooled mortality was lower than in severe burns.Pooled percentage of successful weaning from ECMO was 65%(95%CI 46-84%)and inversely correlated with burn area.The overall rate of ECMO-related complications was 67.46%,and infection(30.77%)and bleedings(23.08%)were the two most common complications.About 49.26%of patients required continuous renal replacement therapy.Conclusions:ECMO seems to be an appropriate rescue therapy for burn patients despite the relatively high mortality and complication rate.Inhalation injury,burn area and ECMO duration are the main factors influencing clinical outcomes.