Impact of Wildfires on Cardiovascular Health.

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

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

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

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.

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.

Opportunities for primary health care: a qualitative study of perinatal health and wellbeing during bushfire crises.

BACKGROUND: During the summer of 2019/2020, Australia experienced a catastrophic wildfire season that affected nearly 80% of Australians either directly or indirectly. The impacts of climate crisis on perinatal health have only recently begun to receive attention. The objective of this study was to understand experiences of perinatal women during the bushfire and smoke events of 2019-2020 regarding health, health care, and public health messaging. METHODS: Semistructured interviews were conducted by phone or web conferencing platforms with 43 participants living in the south-east of Australia who were either pregnant or who had recently had a baby during the 2019/2020 fires. RESULTS: The health impacts on participants of the fires, associated smoke, and evacuations for some, were both physical and psychological. Many participants sought information regarding how to protect their own health and that of their unborn/recently born children, but reported this difficult to find. CONCLUSIONS: Pregnant women and new mothers exposed to bushfire events are a risk group for adverse physical and psychological outcomes. At the time of the 2019/2020 Australian bushfires, exposed women could not easily access evidence-based information to mitigate this risk. Family practitioners are well placed to provide pregnant women and new mothers with this sought-after information, but they need to be prepared well in advance of future similar events.

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.

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.

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.

Development and Application of Multidimensional Lipid Libraries to Investigate Lipidomic Dysregulation Related to Smoke Inhalation Injury Severity.

The implication of lipid dysregulation in diseases, toxic exposure outcomes, and inflammation has brought great interest to lipidomic studies. However, lipids have proven to be analytically challenging due to their highly isomeric nature and vast concentration ranges in biological matrices. Therefore, multidimensional techniques such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (LC-IMS-CID-MS) have been implemented to separate lipid isomers as well as provide structural information and increased identification confidence. These data sets are however extremely large and complex, resulting in challenges for data processing and annotation. Here, we have overcome these challenges by developing sample-specific multidimensional lipid libraries using the freely available software Skyline. Specifically, the human plasma library developed for this work contains over 500 unique lipids and is combined with adapted Skyline functions such as indexed retention time (iRT) for retention time prediction and IMS drift time filtering for enhanced selectivity. For comparison with other studies, this database was used to annotate LC-IMS-CID-MS data from a NIST SRM 1950 extract. The same workflow was then utilized to assess plasma and bronchoalveolar lavage fluid (BALF) samples from patients with varying degrees of smoke inhalation injury to identify lipid-based patient prognostic and diagnostic markers.

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

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

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

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

Evaluation of prehospital hydroxocobalamin use in the setting of smoke inhalation.

BACKGROUND: The indications for prehospital hydroxocobalamin are not well defined. The aim of this study was to evaluate prehospital signs and symptoms in patients who received hydroxocobalamin to improve future use. METHODS: In this retrospective study, all patients who received prehospital Hydroxocobalamin at a tertiary care burn center from December 2012 to March 2018 were reviewed. Each case was evaluated for evidence of suspected cyanide toxicity: hypotension, syncope, CNS depression/altered mentation, seizures, respiratory or cardiac arrest. A determination was made whether or not hydroxocobalamin was indicated. RESULTS: In this study, EMS providers administered hydroxocobalamin to 42 patients between December 2012 and March 2018. The majority (71%) of suspected cyanide exposures were from house fires. The most common prehospital findings were coma or depressed CNS (36%), followed by hypotension (16%) and cardiac arrest (12%). Sixty percent of patients treated with hydroxocobalamin had none of the six clinical indicators for potential cyanide toxicity. Carboxyhemoglobin and serum lactate were significantly different in patients that had a clinical indication for hydroxocobalamin compared to those who did not. CONCLUSIONS: Prehospital hydroxocobalamin was used empirically however, indications are unclear. Using defined clinical indications may provide greater clarity for providers and reduce unnecessary use of hydroxocobalamin.

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

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

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

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

Emerging therapies for smoke inhalation injury: a review.

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.

Quantitative CT Evidence of Airway Inflammation in WTC Workers and Volunteers with Low FVC Spirometric Pattern.

BACKGROUND: The most common abnormal spirometric pattern reported in WTC worker and volunteer cohorts has consistently been that of a nonobstructive reduced forced vital capacity (low FVC). Low FVC is associated with obesity, which is highly prevalent in these cohorts. We used quantitative CT (QCT) to investigate proximal and distal airway inflammation and emphysema in participants with stable low FVC pattern. METHODS: We selected study participants with at least two available longitudinal surveillance spirometries, and a chest CT with QCT measurements of proximal airway inflammation (wall area percent, WAP), end-expiratory air trapping, suggestive of distal airway obstruction (expiratory to inspiratory mean lung attenuation ratio, MLAEI), and emphysema (percentage of lung volume with attenuation below - 950 HU, LAV%). The comparison groups in multinomial logistic regression models were participants with consistently normal spirometries, and participants with stable fixed obstruction (COPD). RESULTS: Compared to normal spirometry participants, and after adjusting for age, sex, race/ethnicity, BMI, smoking, and early arrival at the WTC disaster site, low FVC participants had higher WAP (ORadj 1.24, 95% CI 1.06, 1.45, per 5% unit), suggestive of proximal airway inflammation, but did not differ in MLAEI, or LAV%. COPD participants did not differ in WAP with the low FVC ones and were more likely to have higher MLAEI or LAV% than the other two subgroups. DISCUSSION: WTC workers with spirometric low FVC have higher QCT-measured WAP compared to those with normal spirometries, but did not differ in distal airway and emphysema measurements, independently of obesity, smoking, and other covariates.

Ameliorative effect of acetylshikonin on cigarette smoke-induced lung inflammation in mice.

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Acetylshikonin was the active principle component of Purple Gromwell that show anti-oxidative and anti-inflammatory effect. However, no data are available to elucidate the protective effect of acetylshikonin on COPD. Acetylshikonin could attenuate smoke-induced lung pathological changes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein 1 (MCP-1) productions, and tissue damages caused by oxidative stress. Furthermore, acetylshikonin was found to enhance the expression of Nrf2 and Nur77-mediated COX-2 in vivo and in vitro.

Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature.

Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.

Identification of differentially expressed proteins in the injured lung from zinc chloride smoke inhalation based on proteomics analysis.

BACKGROUND: Lung injury due to zinc chloride smoke inhalation is very common in military personnel and leads to a high incidence of pulmonary complications and mortality. The aim of this study was to uncover the underlying mechanisms of lung injury due to zinc chloride smoke inhalation using a rat model. METHODS: Histopathology analysis of rat lungs after zinc chloride smoke inhalation was performed by using haematoxylin and eosin (H&E) and Mallory staining. A lung injury rat model of zinc chloride smoke inhalation (smoke inhalation for 1, 2, 7 and 14 days) was developed. First, isobaric tags for relative and absolute quantization (iTRAQ) and weighted gene co-expression network analysis (WGCNA) were used to identify important differentially expressed proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to study the biological functions of differentially expressed proteins. Then, analysis of lung injury repair-related differentially expressed proteins in the early (day 1 and day 2) and middle-late stages (day 7 and day 14) of lung injury after smoke inhalation was performed, followed by the protein-protein interaction (PPI) analysis of these differentially expressed proteins. Finally, the injury repair-related proteins PARK7 and FABP5 were validated by immunohistochemistry and western blot analysis. RESULTS: Morphological changes were observed in the lung tissues after zinc chloride smoke inhalation. A total of 27 common differentially expressed proteins were obtained on days 1, 2, 7 and 14 after smoke inhalation. WGCNA showed that the turquoise module (which involved 909 proteins) was most associated with smoke inhalation time. Myl3, Ckm, Adrm1 and Igfbp7 were identified in the early stages of lung injury repair. Gapdh, Acly, Tnni2, Acta1, Actn3, Pygm, Eno3 and Tpi1 (hub proteins in the PPI network) were identified in the middle-late stages of lung injury repair. Eno3 and Tpi1 were both involved in the glycolysis/gluconeogenesis signalling pathway. The expression of PARK7 and FABP5 was validated and was consistent with the proteomics analysis. CONCLUSION: The identified hub proteins and their related signalling pathways may play crucial roles in lung injury repair due to zinc chloride smoke inhalation.

Elevated Neuroglobin Lessens Neuroinflammation and Alleviates Neurobehavioral Deficits Induced by Acute Inhalation of Combustion Smoke in the Mouse.

Acute inhalation of combustion smoke produces long-term neurologic deficits in survivors. To study the mechanisms that contribute to the development of neurologic deficits and identify targets for prevention, we developed a mouse model of acute inhalation of combustion smoke, which supports longitudinal investigation of mechanisms that underlie the smoke induced inimical sequelae in the brain. Using a transgenic mouse engineered to overexpress neuroglobin, a neuroprotective oxygen-binding globin protein, we previously demonstrated that elevated neuroglobin preserves mitochondrial respiration and attenuates formation of oxidative DNA damage in the mouse brain after smoke exposure. In the current study, we show that elevated neuronal neuroglobin attenuates the persistent inflammatory changes induced by smoke exposure in the mouse brain and mitigates concordant smoke-induced long-term neurobehavioral deficits. Specifically, we found that increases in hippocampal density of GFAP and Iba-1 positive cells that are detected post-smoke in wild-type mice are absent in the neuroglobin overexpressing transgenic (Ngb-tg) mice. Similarly, the smoke induced hippocampal myelin depletion is not observed in the Ngb-tg mice. Importantly, elevated neuroglobin alleviates behavioral and memory deficits that develop after acute smoke inhalation in the wild-type mice. Taken together, our findings suggest that the protective effects exerted by neuroglobin in the brains of smoke exposed mice afford protection from long-term neurologic sequelae of acute inhalation of combustion smoke. Our transgenic mouse provides a tool for assessing the potential of elevated neuroglobin as possible strategy for management of smoke inhalation injury.