CDC Guidelines for the Prevention and Treatment of Anthrax, 2023.

This report updates previous CDC guidelines and recommendations on preferred prevention and treatment regimens regarding naturally occurring anthrax. Also provided are a wide range of alternative regimens to first-line antimicrobial drugs for use if patients have contraindications or intolerances or after a wide-area aerosol release of: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. Changes from previous CDC guidelines and recommendations include an expanded list of alternative antimicrobial drugs to use when first-line antimicrobial drugs are contraindicated or not tolerated or after a bioterrorism event when first-line antimicrobial drugs are depleted or ineffective against a genetically engineered resistant: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Pulmonary drug delivery and retention: A computational study to identify plausible parameters based on a coupled airway-mucus flow model.

Pulmonary drug delivery systems rely on inhalation of drug-laden aerosols produced from aerosol generators such as inhalers, nebulizers etc. On deposition, the drug molecules diffuse in the mucus layer and are also subjected to mucociliary advection which transports the drugs away from the initial deposition site. The availability of the drug at a particular region of the lung is, thus, determined by a balance between these two phenomena. A mathematical analysis of drug deposition and retention in the lungs is developed through a coupled mathematical model of aerosol transport in air as well as drug molecule transport in the mucus layer. The mathematical model is solved computationally to identify suitable conditions for the transport of drug-laden aerosols to the deep lungs. This study identifies the conditions conducive for delivering drugs to the deep lungs which is crucial for achieving systemic drug delivery. The effect of different parameters on drug retention is also characterized for various regions of the lungs, which is important in determining the availability of the inhaled drugs at a target location. Our analysis confirms that drug delivery efficacy remains highest for aerosols in the size range of 1-5 µm. Moreover, it is observed that amount of drugs deposited in the deep lung increases by a factor of 2 when the breathing time period is doubled, with respect to normal breathing, suggesting breath control as a means to increase the efficacy of drug delivery to the deep lung. A higher efficacy also reduces the drug load required to be inhaled to produce the same health effects and hence, can help in minimizing the side effects of a drug.

Inhalation of Silver Silicate Nanoparticles Leads to Transient and Differential Microglial Activation in the Rodent Olfactory Bulb.

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.

Real-time monitoring of cellular oxidative stress during aerosol sampling: a proof of concept study.

The Portable In Vitro Exposure Cassette (PIVEC) was developed for on-site air quality testing using lung cells. Here, we describe the incorporation of a sensor within the PIVEC for real time monitoring of cellular oxidative stress during exposure to contaminated air. An electrochemical, enzymatic biosensor based on cytochrome c (cyt c) was selected to measure reactive oxygen species (ROS), including hydrogen peroxide and super oxides, due to the stability of signal over time. Human A549 lung cells were grown at the air-liquid interface and exposed within the PIVEC to dry 40 nm copper nanoparticle aerosols for 10 minutes. The generation of ROS compounds was measured during exposure and post-exposure for one hour using the biosensor and compared to intracellular ROS determined using the 2',7'-dichlorodihydrofluoroscein diacetate (DCFH-DA) assay. A similar increase in oxidative stress upon aerosol exposure was measured using both the cyt c biosensor and DCFH-DA assay. The incorporation of a biosensor within the PIVEC is a unique, first-of-its-kind system designed to monitor the real-time effect of aerosols.

Integrative Analysis of lncRNA-mRNA Coexpression in Human Lung Epithelial Cells Exposed to Dimethyl Selenide-Derived Secondary Organic Aerosols.

Dimethyl selenide (DMSe) is one of the major volatile organoselenium compounds released into the atmosphere through plant metabolism and microbial methylation. DMSe has been recently revealed as a precursor of secondary organic aerosol (SOA), and its resultant SOA possesses strong oxidizing capability toward thiol groups that can perturb several major biological pathways in human airway epithelial cells and is linked to genotoxicity, DNA damage, and p53-mediated stress responses. Mounting evidence has suggested that long noncoding RNAs (lncRNAs) are involved in stress responses to internal and environmental stimuli. However, the underlying molecular interactions remain to be elucidated. In this study, we performed integrative analyses of lncRNA-mRNA coexpression in the transformed human bronchial epithelial BEAS-2B cell line exposed to DMSe-derived SOA. We identified a total of 971 differentially expressed lncRNAs in BEAS-2B cells exposed to SOA derived from O3 and OH oxidation of DMSe. Gene ontology (GO) network analysis of cis-targeted genes showed significant enrichment of DNA damage, apoptosis, and p53-mediated stress response pathways. trans-Acting lncRNAs, including PINCR, PICART1, DLGAP1-AS2, and LINC01629, known to be associated with human carcinogenesis, also showed altered expression in cell treated with DMSe-SOA. Overall, this study highlights the regulatory role of lncRNAs in altered gene expression induced by DMSe-SOA exposure.

Pathogenesis-based preexposure prophylaxis associated with a low risk of SARS-CoV-2 infection in healthcare workers at a designated COVID-19 hospital: a pilot study.

BACKGROUND: At present, no agents are known to be effective at preventing COVID-19. Based on current knowledge of the pathogenesis of this disease, we suggest that SARS-CoV-2 infection might be attenuated by directly maintaining innate pulmonary redox, metabolic and dilation functions using well-tolerated medications that are known to serve these functions, specifically, a low-dose aerosolized combination of glutathione, inosine and potassium. METHODS: From June 1 to July 10, 2020, we conducted a pilot, prospective, open-label, single-arm, single-center study to evaluate the safety and efficacy of preexposure prophylaxis (PrEP) with aerosolized combination medication (ACM) on the incidence of SARS-CoV-2 positivity in 99 healthcare workers (HCWs) at a hospital designated for treating COVID-19 patients. We compared SARS-CoV-2 positivity in ACM users to retrospective data collected from 268 untreated HCWs at the same hospital. Eligible participants received an aerosolized combination of 21.3 mg/ml glutathione and 8.7 mg/ml inosine in 107 mM potassium solution for 14 days. The main outcome was the frequency of laboratory-confirmed SARS-CoV-2 cases, defined as individuals with positive genetic or immunological tests within 28 days of the study period. RESULTS: SARS-CoV-2 was detected in 2 ACM users (2, 95% CI: 0.3 to 7.1%), which was significantly less than the incidence in nonusers, at 24 (9, 95% CI: 5.8 to 13.0%; P = 0.02). During the PrEP period, solicited adverse events occurred in five participants; all were mild and transient reactions. CONCLUSIONS: Our findings might be used either to prevent SARS-CoV-2 infection or to support ongoing and new research into more effective treatments for COVID-19. TRIAL REGISTRATION: ISRCTN, ISRCTN34160010 . Registered 14 September 2020 - Retrospectively registered.

Comparison between microcatheter and nebulizer for generating Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

BACKGROUND: This study compares an endoscopic microcatheter and a nebulizer for delivering Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). METHODS: This is an in vitro and ex vivo study in an established model (inverted bovine urinary bladder). Four parameters were compared to determine the performance of a micro-perforated endoscopic spray catheter vs. state-of-the art, nozzle technology: (1) surface coverage and pattern with methylene blue on blotting paper at three different distances; (2) median aerodynamic diameter (MAD) of aerosol droplets with three different solutions (H2O, Glc 5% and silicon oil); (3) depth of tissue penetration of doxorubicin (DOX) and (4) tissue concentration of cisplatin (CIS) and DOX using standard clinical solutions. RESULTS: The spray area covered by the microcatheter was larger (p < 0.001) but its pattern was inhomogenous than with the nozzle technology. We found that aerosol droplets were larger in the test group than in the control group for all three solutions tested. Median tissue penetration of DOX was lower (980 µm) with the microcatheter than with the nebulizer (1235 µm) and distribution was more heterogeneous ( = 0.003) with the microcatheter. The median tissue concentration of DOX and CIS was lower and concentration of DOX was more heterogeneous with the microcatheter (p = 0.002). CONCLUSIONS: This investigation has revealed that microcatheter technology generates larger aerosol droplet size, less drug tissue penetration and lower drug tissue concentration than the current nozzle technology. In the absence of clinical studies, use of microcatheters for delivering PIPAC can not be recommended at this stage.

Evaluation of potential toxicity of Steriplant©N aerosolization toward human alveolar cells A459 in vitro.

Protection of patients against hospital-acquired infections is of major importance. Disinfection of magnetic resonance imaging suites is, due to their unique properties and environment particularly, difficult to implement. We developed an OPTI-JET CS MD 2ZE aerosolizator for disinfection of a magnetic resonance imaging suite using the electrolyzed oxidizing water biocide Steriplant©N. The disinfection of the magnetic resonance imaging suite with this system reduced from the number of colony formed unit/m3 air by 87% and 96% in 6 and 15 min of disinfection, respectively. It is well known that exposure of personnel or patients to aerosols may represent risk to the respiratory system; therefore, the aim of this study was to assess potential cytotoxicity and genotoxicity of Steriplant©N aerosolization toward human alveolar cells A459 in vitro. The A459 cells were exposed to aerosol containing different concentrations (50% and 100% v/v) of Steripalnt©N for 6 min in a chamber that had been constructed to simulate the conditions in the magnetic resonance imaging suite. The cytotoxicity was evaluated by measuring iodide uptake, and the genotoxicity was determined by measuring formation of phosphorylated H2AX histones, a marker for deoxyribonucleic acid double-strand breaks, immediately after the aerosolization and after 1, 4, and 24 h postincubation. The results demonstrated that aerosolization with Steriplant©N at conditions reflecting aerosolization in a magnetic resonance imaging suite is not cytotoxic and does not exhibit genotoxic potential in vitro.

Development and Characterization of Treprostinil Palmitil Inhalation Aerosol for the Investigational Treatment of Pulmonary Arterial Hypertension.

Treprostinil palmitil (TP) is a prodrug of treprostinil (TRE), a pulmonary vasodilator that has been previously formulated for inhaled administration via a nebulizer. TP demonstrates a sustained presence in the lungs with reduced systemic exposure and prolonged inhibition of hypoxia-induced pulmonary vasoconstriction in vivo. Here, we report on re-formulation efforts to develop a more convenient solution-based metered-dose inhaler (MDI) formulation of TP, a treprostinil palmitil inhalation aerosol (TPIA) that matches the pharmacokinetic (PK) and efficacy profile of a nebulized TP formulation, treprostinil palmitil inhalation suspension (TPIS). MDI canisters were manufactured using a two-stage filling method. Aerosol performance, formulation solubility, and chemical stability assays were utilized for in vitro evaluation. For in vivo studies, TPIA formulations were delivered to rodents using an inhalation tower modified for MDI delivery. Using an iterative process involving evaluation of formulation performance in vitro (TP and excipient solubility, chemical stability, physical stability, and aerosol properties) and confirmatory testing in vivo (rat PK and efficacy, guinea pig cough), a promising formulation was identified. The optimized formulation, TPIA-W, demonstrates uniform in vitro drug delivery, a PK profile suitable for a once-daily administration, efficacy lasting at least 12 h in a hypoxic challenge model, and a significantly higher cough threshold than the parent drug treprostinil.

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice.

Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer-binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARγ (peroxisome proliferator-activated receptor γ) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.

Electronic Nicotine Delivery System Aerosol-induced Cell Death and Dysfunction in Macrophages and Lung Epithelial Cells.

Electronic nicotine delivery system (ENDS) use is outpacing our understanding of its potential harmful effects. Homeostasis of the lung is maintained through proper balance of cell death, efferocytic clearance, and phagocytosis of pathogens. To investigate whether ENDS use has the potential to alter this balance, we developed physiologically relevant ENDS exposure paradigms for lung epithelial cells and primary macrophages. In our studies, cells were exposed directly to aerosol made from carefully controlled components with and without nicotine. We found that ENDS aerosol exposure led to apoptosis, secondary necrosis, and necrosis in lung epithelial cell models. In contrast, macrophages died mostly by apoptosis and inflammatory caspase-mediated cell death when exposed to ENDS aerosol. The clearance of dead cells and pathogens by efferocytosis and phagocytosis, respectively, is an important process in maintaining a healthy lung. To investigate the impact of ENDS aerosol on macrophage function independent of general toxicity, we used an exposure time that did not induce cell death in primary macrophages. Exposure to ENDS aerosol containing nicotine inhibited nearly all phagocytic and greatly reduced the efferocytic abilities of primary macrophages. When challenged with a bacterial pathogen, there was decreased bacterial clearance. The presence of nicotine in the ENDS aerosol increased its toxicity and functional impact; however, nicotine exposure alone did not have any deleterious effects. These data demonstrate that ENDS aerosol exposure could lead to increased epithelial cell and macrophage death in the lung and impair important macrophage functions that are essential for maintenance of lung function.

In Vitro Toxicity and Chemical Characterization of Aerosol Derived from Electronic Cigarette Humectants Using a Newly Developed Exposure System.

In the United States, the recent surge of electronic cigarette (e-cig) use has raised questions concerning the safety of these devices. This study seeks to assess the pro-inflammatory and cellular stress effects of the vaped humectants propylene glycol (PG) and glycerol (GLY) on airway epithelial cells (16HBE cells and differentiated human bronchial epithelial cells) with a newly developed aerosol exposure system. This system allows for chemical characterization of e-cig generated aerosol particles as well as in vitro exposures of 16HBE cells at an air-liquid interface to vaped PG and GLY aerosol. Our data demonstrate that the process of vaping results in the formation of PG- and GLY-derived oligomers in the aerosol particles. Our in vitro data demonstrate an increase in pro-inflammatory cytokines IL-6 and IL-8 levels in response to vaped PG and GLY exposures. Vaped GLY also causes an increase in cellular stress signals HMOX1, NQO1, and carbonylated proteins when the e-cig device is operated at high wattages. Additionally, we find that the exposure of vaped PG causes elevated IL-6 expression, while the exposure of vaped GLY increases HMOX1 expression in human bronchial epithelial cells when the device is operated at high wattages. These findings suggest that vaporizing PG and GLY results in the formation of novel compounds and the exposure of vaped PG and GLY are detrimental to airway cells. Since PG and/or GLY is universally contained in all e-cig liquids, we conclude that these components alone can cause harm to the airway epithelium.

Isoprene-Derived Secondary Organic Aerosol Induces the Expression of MicroRNAs Associated with Inflammatory/Oxidative Stress Response in Lung Cells.

Exposure to fine particulate matter (PM2.5), of which secondary organic aerosol (SOA) is a major constituent, is linked to adverse health outcomes, including cardiovascular disease, lung cancer, and preterm birth. Atmospheric oxidation of isoprene, the most abundant nonmethane hydrocarbon emitted into Earth's atmosphere primarily from vegetation, contributes to SOA formation. Isoprene-derived SOA has previously been found to alter inflammatory/oxidative stress genes. MicroRNAs (miRNAs) are epigenetic regulators that serve as post-transcriptional modifiers and key mediators of gene expression. To assess whether isoprene-derived SOA alters miRNA expression, BEAS-2B lung cells were exposed to laboratory-generated isoprene-derived SOA constituents derived from the acid-driven multiphase chemistry of authentic methacrylic acid epoxide (MAE) or isomeric isoprene epoxydiols (IEPOX) with acidic sulfate aerosol particles. These IEPOX- and MAE-derived SOA constituents have been shown to be measured in large quantities within PM2.5 collected from isoprene-rich areas affected by acidic sulfate aerosol particles derived from human activities. A total of 29 miRNAs were identified as differentially expressed when exposed to IEPOX-derived SOA and 2 when exposed to MAE-derived SOA, a number of which are inflammatory/oxidative stress associated. These results suggest that miRNAs may modulate the inflammatory/oxidative stress response to SOA exposure, thereby advancing the understanding of airway cell epigenetic response to SOA.

Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

Chemical Elements in Electronic Cigarette Solvents and Aerosols Inhibit Mitochondrial Reductases and Induce Oxidative Stress.

INTRODUCTION: Chemical elements and their toxicity were evaluated in electronic cigarette (EC) solvents, fluids, and aerosols. AIMS AND METHODS: Element identification and quantification in propylene glycol (PG), glycerin (G), refill fluids before and after use, and aerosols was done using inductively coupled plasma optical emission spectrometry. Cytotoxicity and oxidative stress were evaluated using in vitro assays. RESULTS: Seven elements were present in PG, G, and popular refill fluids, and they transferred to aerosols made with ECs. Selenium was in all products (0.125-0.292 mg/L), while arsenic, aluminum, and tin were frequently in solvent and refill fluid samples at lower concentrations. Iron, chromium, copper, nickel, zinc, and lead were only detected in fluid after EC use, indicating they came from heated atomizers. Elements transferred most efficiently to aerosols made with second-/third-generation ECs. Of the elements in fluid, selenium and arsenic were the most cytotoxic to human bronchial epithelial cells (BEAS-2B) and pulmonary fibroblasts in the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Selenium increased superoxide production in mitochondria and nucleoli and elevated selenoprotein H in nucleoli of BEAS-2B cells at concentrations found in EC aerosols (10 nM or 0.002 mg/L). CONCLUSIONS: Elements in EC aerosols came from both e-fluids and atomizing units. Within second-/third-generation products, transfer became more efficient as power increased. In vitro responses occurred at concentrations of selenium found in some EC aerosols. Human exposure to chemical elements in ECs could be reduced by regulating (decreasing) allowable EC power and by improving the purity of PG and G. IMPLICATIONS: PG, G, refill fluids, and e-fluids contained potentially toxic chemical elements that transferred to aerosols. Transfer was more efficient in second- and third-generation EC products and increased as power increased. Selenium and arsenic were the most cytotoxic of the elements tested in the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Selenium tetrachloride-induced oxidative stress in BEAS-2B cells, but not in human pulmonary fibroblasts. All fluids contained selenium above the concentration that induced oxidative stress in human bronchial epithelial cells. Selenium increased superoxide in mitochondria and nucleoli and increased selenoprotein H, a redox responsive DNA-binding protein that is upregulated by superoxide and an indicator of nucleolar stress. EC users are exposed to elements in aerosols, which may with chronic exposure contribute to diseases associated with oxidative stress.

Aerosolizable Marine Phycotoxins and Human Health Effects: In Vitro Support for the Biogenics Hypothesis.

Respiratory exposure to marine phycotoxins is of increasing concern. Inhalation of sea spray aerosols (SSAs), during harmful Karenia brevis and Ostreopsis ovata blooms induces respiratory distress among others. The biogenics hypothesis, however, suggests that regular airborne exposure to natural products is health promoting via a downregulation of the mechanistic target of rapamycin (mTOR) pathway. Until now, little scientific evidence supported this hypothesis. The current explorative in vitro study investigated both health-affecting and potential health-promoting mechanisms of airborne phycotoxin exposure, by analyzing cell viability effects via cytotoxicity assays and effects on the mTOR pathway via western blotting. To that end, A549 and BEAS-2B lung cells were exposed to increasing concentrations (ng·L-1 - mg·L-1) of (1) pure phycotoxins and (2) an extract of experimental aerosolized homoyessotoxin (hYTX). The lowest cell viability effect concentrations were found for the examined yessotoxins (YTXs). Contradictory to the other phycotoxins, these YTXs only induced a partial cell viability decrease at the highest test concentrations. Growth inhibition and apoptosis, both linked to mTOR pathway activity, may explain these effects, as both YTXs were shown to downregulate this pathway. This proof-of-principle study supports the biogenics hypothesis, as specific aerosolizable marine products (e.g., YTXs) can downregulate the mTOR pathway.

Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases.

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

Development of Aggregation-Caused Quenching Probe-Loaded Pressurized Metered-Dose Inhalers with Fluorescence Tracking Potentials.

Recently, pressurized metered-dose inhalers (pMDIs) are getting more attention as an effective approach of pulmonary drug delivery, and nanoparticle-based formulations have become a new generation of pMDIs, especially for water insoluble drugs. Up until now, there is no clinical application of nanoparticle-based pMDIs. The main hurdle remains in the lack of knowledge of the in vivo fate of those systems. In this study, a fluorescent probe named P4 with aggregation-caused quenching (ACQ) effect was loaded in the nanoparticle-based pMDIs to track the in vivo fate. P4 probe expressed strong fluorescence when distributed in intact nanoparticles, but quenched in the in vivo aqueous environment due to molecular aggregation. Experimentally, P4 probe was encapsulated into solid lipid nanoparticles (SLN) as P4-SLN, and then, the formulation of pMDIs was optimized. The content (w/w) of the optimal formulation (P4-SLN-pMDIs) was as follows: 6.02% Pluronic® L64, 12.03% ethanol, 0.46% P4-SLN, and 81.49% 1,1,1,2-tetrafluoroethane (HFA-134a). P4-SLN-pMDI was transparent in appearance, possessed a particle size of 132.07 ± 3.56 nm, and the fine particle fraction (FPF) was 39.53 ± 1.94%, as well good stability was shown within 10 days. The results indicated P4-SLN-pMDI was successfully prepared. Moreover, the ACQ property of P4-SLN-pMDIs was verified, which ensured the fluorescence property as a credible tool for in vivo fate study. Taken together, this work established a platform that could provide a firm theoretical support for exploration of the in vivo fate of nanoparticle-based pMDIs in subsequent studies. Grapical abstract.

Preventing Viral Contamination: Effects of Wipe and Spray-based Decontamination of Gloves and Gowns.

We conducted a laboratory simulation to evaluate the contamination of environmental surfaces when using wipe vs spray methods of personal protective equipment (PPE) decontamination. We did not observe any environmental contamination with the bacteriophage MS-2 when bleach solution spray or wipes were used for PPE disinfection.