Severity of inhalation injury and risk of nosocomial pneumonia: a retrospective cohort study.

BACKGROUND: The impact of inhalation injury on risk of nosocomial pneumonia, an important complication in burn patients, is not well established. RESEARCH QUESTION: Is more severe inhalation injury associated with increased risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of patients with suspected inhalation injury admitted to a regional burn center from 2011 to 2022 who underwent diagnostic bronchoscopy within 48 hours of admission. We estimated the association of high-grade inhalation injury (abbreviated injury score [AIS] 3-4) versus low-grade inhalation injury (AIS 1-2) with nosocomial pneumonia (NP) adjusted for age, burn size, and comorbid obstructive lung disease. Death and hospital discharge were considered competing risks. RESULTS: Of the 245 patients analyzed, 51 (21%) had high-grade injury, 180 (73%) had low-grade injury, and 14 (6%) had no inhalation injury. Among the 236 patients hospitalized for >48 hours, NP occurred in 24/50 (48%) patients in the high-grade group, 54/172 (31%) in the low-grade group, and 2/14 (14%) in the no inhalation injury group. High-grade (vs low-grade) inhalation injury was associated with higher hazard of NP in both the proportional cause-specific hazard model (CSHR 2.04; 95% CI, 1.26-3.30; p=0.004) and Fine-Gray subdistribution hazards model (SHR for NP, 2.24; 95% CI, 1.38-3.64; p=0.001). INTERPRETATION: Among patients with inhalation injury, more severe injury was associated with higher hazard of NP in competing risk analysis. Additional research is needed to investigate mechanisms that may explain the relationship between inhalation injury and NP and to identify more effective prevention strategies.

Carbon Monoxide-Related Vision Loss in an Acute Burn Patient.

Carbon monoxide poisoning can occur as part of smoke exposure in the burn population. Here we report the case of a 32-year-old, previously healthy male, with carbon monoxide-related blindness after smoke exposure in an apartment fire. Cerebral hypoperfusion was diagnosed using magnetic resonance imaging of the brain, and the patient was diagnosed with cortical visual impairment. He was treated with hyperbaric oxygen therapy following which he had partial recovery of his vision. There is a paucity of information regarding this phenomenon and its treatment.

How to Personalize General Anesthesia-A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning.

Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.

The Impact of Electrocautery Smoke on Surgical Staff and the Efficacy of Normal Surgical Masks Versus N95 Masks.

Electrocautery is a commonly used technique in surgical procedures, generating smoke that poses health risks to surgical staff. This study investigates the comparative efficacy of normal surgical masks versus N95 masks in mitigating the harmful effects of electrocautery smoke. Through a systematic review of literature spanning two decades, we explore the causes and effects of electrocautery smoke exposure, including potential long-term inhalation effects. Our findings highlight significant disparities in the protection offered by different masks and underscore the importance of adequate respiratory protection in surgical settings. In addition, we examine the factors influencing the generation and composition of electrocautery smoke, such as the power settings used, the type of tissue being cauterized, and the duration of the procedure. Furthermore, we discuss the potential health risks associated with long-term exposure to electrocautery smoke, including the possibility of respiratory conditions, cardiovascular effects, and carcinogenicity. Our analysis also addresses the importance of implementing appropriate smoke evacuation systems and optimizing operating room ventilation to minimize the concentration of smoke particles in the surgical environment. Overall, this comprehensive analysis provides valuable insights into the impact of electrocautery smoke in surgical settings and the varying levels of protection offered by different masks.

Impact of Wildfires on Cardiovascular Health.

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

El humo del electrocauterio, el riesgo olvidado y minimizado de la cirugía / Smoke from electrocautery, the forgotten and minimized risk of surgery

Introducción. La nueva era de la cirugía es cada vez más dependiente de la tecnología, y un ejemplo de ello es el uso generalizado de electrocauterio como parte primordial de la práctica quirúrgica. El humo quirúrgico es un subproducto de la disección y la coagulación de los tejidos producidas por los equipos de energía, que representa múltiples riesgos potenciales para la salud del grupo quirúrgico, sin embargo, se han minimizado los peligros causados por la exposición de manera frecuente y acumulativa a este aerosol. Métodos. Se realizó un análisis crítico, desde una posición reflexiva de la información disponible, estableciendo los posibles riesgos relacionados con la exposición al humo quirúrgico. Discusión. Es visible la necesidad imperativa de establecer directrices nacionales, pautas normativas y recomendaciones estandarizadas para cumplir con las exigencias dadas por los sistemas de gestión en salud ocupacional y seguridad del trabajo, cuyo objetivo principal es hacer efectivo el uso de mascarillas quirúrgicas apropiadas, la implementación de programa de vigilancia epidemiológica ambiental en sala de cirugía, la priorización del uso constante de aspiradores y sistemas de evacuación, y la ejecución de programas educativos de sensibilización dirigidos al personal implicado. De igual manera, se abre la inquietud de la necesidad de nuevos estudios para definir con mayor precisión el peligro de este aerosol. Conclusión. Se recomienda de manera responsable utilizar todas las estrategias preventivas existentes para intervenir en salas de cirugía los riesgos minimizados y olvidados del humo quirúrgico.

Introduction. The new era of surgery is increasingly dependent on technology, and an example of this is the widespread use of electrocautery as a primary part of surgical practice. Surgical smoke is a byproduct of the dissection and coagulation of tissues produced by energy equipment, which represents multiple potential health risks for the surgical group; however, the dangers caused by cumulative exposure have been minimized. Methods. A critical analysis was carried out from a reflective position of the available information, establishing the possible risks related to exposure to surgical smoke. Discussion. The imperative need to establish national normative guidelines and standardized recommendations to comply with the demands given by the occupational health and work safety management systems, whose main objective is to make effective the use of appropriate surgical masks, implementation of environmental epidemiological surveillance program in the operating room, prioritizing the constant use of vacuum cleaners and evacuation systems, and carrying out educational awareness programs aimed at the personnel involved. Likewise, there is concern about the need for new studies to more precisely define the danger of this aerosol. Conclusion. It is recommended to responsibly use all existing preventive strategies to intervene in operating rooms to minimize the forgotten risks of surgical smoke.

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

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

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

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

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

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

Toxic chemical exposures among civilians in armed conflicts: the need for research equity, justice, and accountability.

OBJECTIVE: Armed conflicts result in the release of toxic chemicals into the surrounding environment and civilians are commonly exposed to these toxicants.This paper reviews the evidence on civilian exposure to toxic chemicals, including but not limited to inhaled toxic substances, in post-World War II armed conflicts, and proposes a framework for the implementation of long-term surveillance programs for these populations. MATERIALS AND METHODS: Four databases of peer-reviewed health articles were searched for all English-language articles with a primary focus on toxic chemical exposures among civilians in armed conflicts since World War II. The review was supplemented substantially by the gray literature. RESULTS: In the 66 articles that met the inclusion criteria, the authors categorized the chemical toxicants to which civilians have been exposed in modern armed conflicts as ubiquitous (e.g. smoke, dust, and munitions components present in all conflicts) or particular agents (e.g. specific chemical agents used in a few conflicts). While most studies focused on particular agents, the vast majority of civilians are in fact exposed to ubiquitous agents both in the acute conflict phase and through persistent environmental exposures after the cessation of hostilities. DISCUSSION/CONCLUSION: There is a dearth of research concerning civilian exposures to toxic chemicals during armed conflicts. In line with principles of equity, justice, and accountability, robust research and surveillance programs are urgently needed to document exposures and provide ongoing assessments and any necessary treatment for these long-ignored populations, most of whom live in the Global South.

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

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

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

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

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

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

Surgical smoke and the orthopedic surgeon: a non-systematic review of the hazards and strategies for mitigating risk.

INTRODUCTION: Surgical smoke generated through the use of electrical surgical devices poses a risk to the surgeon, medical personnel in the operating room, and the patient by exposing them to environmentally hazardous particulate matter. Previous investigation has shown that surgical smoke leads to an increased risk of pulmonary conditions, circulatory disorders, and irritation of the eyes, nose, and throat. Transmission of infectious disease can occur through inhalation of viral particles, and the presence of carcinogens are also of major concern. The deleterious effects of surgical smoke are well documented in several subspecialties, namely dermatology and general surgery, but there has been little discussion on the topic amongst orthopedic surgeons. METHODS: A non-systematic review of the literature was completed with the aim of identifying the major categories of adverse health effects associated with surgical smoke inhalation and offering recommendations to reduce these hazards in the orthopedic surgical community. RESULTS: Three primary categories of risk associated with surgical smoke inhalation were identified: inflammation, viral/bacterial transmission, and carcinogenicity. In addition, strategies for mitigating risk and best practice recommendations were explored. CONCLUSION: Surgical smoke is an under-recognized occupational hazard within the orthopedic surgery literature. There are several strategies which can be employed to reduce risk. Further investigation is needed to understand the long-term impact of these risks, as well as what can be done to improve the practicality and compliance with protective measures.

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

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

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

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

Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.

Acute lung injury (ALI) is a syndrome of acute inflammation, barrier disruption, and hypoxemic respiratory failure associated with high morbidity and mortality. Diverse conditions lead to ALI, including inhalation of toxic substances, aspiration of gastric contents, infection, and trauma. A shared mechanism of acute lung injury is cellular toxicity from damage-associated molecular patterns (DAMPs), including extracellular histones. We recently described the selection and efficacy of a histone-binding RNA aptamer (HBA7). The current study aimed to identify the effects of extracellular histones in the lung and determine if HBA7 protected mice from ALI. Histone proteins decreased metabolic activity, induced apoptosis, promoted proinflammatory cytokine production, and caused endothelial dysfunction and platelet activation in vitro. HBA7 prevented these effects. The oropharyngeal aspiration of histone proteins increased neutrophil and albumin levels in bronchoalveolar lavage fluid (BALF) and precipitated neutrophil infiltration, interstitial edema, and barrier disruption in alveoli in mice. Similarly, inhaling wood smoke particulate matter, as a clinically relevant model, increased lung inflammation and alveolar permeability. Treatment by HBA7 alleviated lung injury in both models of ALI. These findings demonstrate the pulmonary delivery of HBA7 as a nucleic acid-based therapeutic for ALI.

Surgical smoke: A hidden killer in the operating room.

Surgical smoke is a byproduct of aerosols containing several components produced by energy equipment. The characteristics of surgical smoke components produced by different types of tissues or using different kinds of energy devices vary. For example, the average diameter of smoke particles produced by electrocautery is smaller, and the possibility of viable cells and pathogens in surgical smoke produced by an ultrasonic knife is higher. According to the characteristics of its composition, surgical smoke may be an important risk factor affecting the health and safety of operating room staff and patients. The use of surgical masks, suction devices and portable smoke evacuation systems can reduce this risk to some extent. However, most operating room staff members do not implement corresponding measures to protect themselves. In this paper, the characteristics of surgical smoke and the research progress in protective measures are briefly reviewed.

Noncardiogenic pulmonary edema in small animals.

OBJECTIVE: To review various types of noncardiogenic pulmonary edema (NCPE) in cats and dogs. ETIOLOGY: NCPE is an abnormal fluid accumulation in the lung interstitium or alveoli that is not caused by cardiogenic causes or fluid overload. It can be due to changes in vascular permeability, hydrostatic pressure in the pulmonary vasculature, or a combination thereof. Possible causes include inflammatory states within the lung or in remote tissues (acute respiratory distress syndrome [ARDS]), airway obstruction (post-obstructive pulmonary edema), neurologic disease such as head trauma or seizures (neurogenic pulmonary edema), electrocution, after re-expansion of a collapsed lung or after drowning. DIAGNOSIS: Diagnosis of NCPE is generally based on history, physical examination, and diagnostic imaging. Radiographic findings suggestive of NCPE are interstitial to alveolar pulmonary opacities in the absence of signs of left-sided congestive heart failure or fluid overload such as cardiomegaly or congested pulmonary veins. Computed tomography and edema fluid analysis may aid in the diagnosis, while some forms of NCPE require additional findings to reach a diagnosis. THERAPY: The goal of therapy for all types of NCPE is to preserve tissue oxygenation and reduce the work of breathing. This may be achieved by removing the inciting cause (eg, airway obstruction) and cage rest in mild cases and supplemental oxygen in moderate cases and may require mechanical ventilation in severe cases. PROGNOSIS: Prognosis is generally good for most causes of veterinary NCPE except for ARDS, although data are scarce for some etiologies of NCPE.

World Trade Center Health Program best practices for the diagnosis and treatment of fibrosing interstitial lung diseases.

Interstitial lung diseases (ILDs) are a diverse set of related conditions with multiple etiologies, in addition to a group where the cause is unknown. There is concern for a potential association of WTC-related exposures with ILD, but the disease range has not differed from what is observed in the general population, and active investigations to study that association are ongoing. Although these diseases are very diverse, some are extremely rare, and they often are disabling and have a poor prognosis, evidence-based guidelines for their diagnosis, management and long-term monitoring have emerged and will evolve as knowledge and therapeutic options increase. This brief article summarizes pertinent issues of diagnosis and management of ILDs, applicable to the diverse group of ILDs that have been observed in the WTC Health Program covered population.