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Exposure to wildfire smoke and dust can severely affect air quality and health. Although particulate matter (PM) levels and exposure are well-established metrics linking to health outcomes, they do not consider differences in particle toxicity or deposition location in the respiratory tract (RT). Usage of the oxidative potential (OP) exposure may further shape our understanding on how different pollution events impact health. Towards this goal, we estimate the aerosol deposition rates, OP and resulting OP deposition rates in the RT for a typical adult Caucasian male residing in Athens, Greece. We focus on a period when African dust (1-3 of August 2021) and severe wildfires at the northern part of the Attika peninsula and the Evia island, Greece (4-18 of August 2021) affected air quality in Athens. During these periods, the aerosol levels increased twofold leading to exceedances of the World Health Organization (WHO) [15(5) μg m -3 ] PM 10 (PM 2.5 ) air quality standard by almost 100 %. We show that the OP exposure is 1.5-times larger during the wildfire smoke events than during the dust intrusion, even if the latter was present in higher mass loads - because wildfire smoke has a higher specific OP than dust. This result carries two important implications: OP exposure should be synergistically used with other metrics - such as PM levels - to efficiently link aerosol exposure with the resulting health effects, and, certain sources of air pollution (in our case, exposure to biomass burning smoke) may need to be preferentially controlled, whenever possible, owing to their disproportionate contribution to OP exposure and ability to penetrate deeper into the human RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Ultrafine particles (UFPs) in urban air environments have been an essential public health concern. The inhalation of UFPs can introduce transition metals contained in the UFP into the human airways, leading to adverse health effects. Therefore, it is crucial to investigate urban air UFP exposure and health risks induced by transition metals. This research carried out a series of field measurements to study urban air UFP exposure in the Greater Houston Area. Three sampling sites in the Greater Houston Area representing varying levels of UFP exposures were selected. The newly developed Mobile Aerosol Lung Deposition Apparatus (MALDA) which consists of a complete set of human airway replicas and a pair of UFP particle sizers was deployed in the sampling sites during three sampling timeframes (morning rush hours, noon, and afternoon rush hours) to obtain on-site UFP respiratory deposition data. UFP samples were collected at the sampling sites for metal composition analysis. The acquired UFP respiratory deposition data and UFP composition data were then used to calculate the respiratory deposited mass of transition metals and estimate the associated health risks for individuals living near sampling sites. Our results showed that transition metal-induced non-cancer risks caused by exposure to urban UFPs were within acceptable limits. The estimated lifetime excess cancer risks were generally <10 -6 , indicating an overall acceptable level of transition metal-induced cancer risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Black carbon (BC) has a significantly negative impact on air quality, climate and human health. Here we investigated the sources and health effects of BC in urban area of the Pearl River Delta (PRD) based on online data measured by Aerodyne soot particle high-resolution time of flight aerosol mass spectrometer (SP-AMS). In urban PRD, BC particles mainly came from vehicle emissions especially heavy-duty vehicle exhausts (contributing 42.9 % of total BC mass concentration), long-range transport (27.6 %), and aged biomass combustion emissions (22.3 %). Indicated by source analysis using simultaneous aethalometer data, BC associated with local secondary oxidation and transport may also be originated from fossil fuel combustion, especially traffic sources in urban and surrounding areas. Size-resolved BC mass concentrations provided by SP-AMS, for the first time to our best knowledge, were used to calculate BC deposition in the human respiratory tract (HRT) of different populations (children, adults, and the elderly) by the Multiple-Path Particle Dosimetry (MPPD) model. We found that submicron BC was deposited more in the pulmonary (P) region (49.0-53.2 % of the total BC deposition dose), while less in the tracheobronchial (TB, 35.6-37.2 %) and head (HA, 11.2-13.8 %) regions. Adults suffered the highest BC deposition (1.19 μg day -1 ) than the elderly (1.09 μg day -1 ) and children (0.25 μg day -1 ). BC deposition rate was greater at night (especially 18:00-24:00) than during the daytime. The maximum deposition in the HRT was found for BC particles around 100 nm, mainly in deeper respiratory regions (TB and P), which may cause more serious health effects. Adults and the elderly group are confronted with the notable carcinogenic risk of BC in the urban PRD, up to 29 times higher than the threshold. Our study emphasizes the need to control BC pollution in the urban area, especially nighttime vehicle emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fine particulate matter is a leading air pollutant, and its composition profile relates to sources and health effects. The human respiratory tract hosts a warmer and more humid microenvironment in contrast with peripheral environments. However, how the human respiratory tract impacts the transformation of the composition of environmental PM 2.5 once they are inhaled and consequently changes of source contribution and health effects are unknown. Here, we show that the respiratory tract can make these properties of PM 2.5 reaching the lung different from environmental PM 2.5 . We found via an in vitro model that the warm and humid conditions drive the desorption of nitrate (about 60%) and ammonium (about 31%) out of PM 2.5 during the inhalation process and consequently make source contribution profiles for respiratory tract-deposited PM 2.5 different from that for environmental PM 2.5 as suggested in 11 Chinese cities and 12 US cities. We also observed that oxidative potential, one of the main health risk causes of PM 2.5 , increases by 41% after PM 2.5 travels through the respiratory tract model. Our results reveal that PM 2.5 inhaled in the lung differs from environmental PM 2.5 . This work provides a starting point for more health-oriented source apportionment, physiology-based health evaluation, and cost-effective control of PM 2.5 pollution.

Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Studies investigating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels in the respiratory system of healthy subjects are scarce. Moreover, separate studies on the health-related outcomes of air pollution for each sex are limited. The current panel study investigated sex-specific Nrf2 expression levels and related oxidative stress and inflammatory responses among healthy adolescents exposed to PM 2.5 , PM 10 , O 3 , and PM 2.5 -bounded metals in a high traffic region. Forty-nine healthy nonsmoking subjects participated in the study for five consecutive months (Nov. 2019 to Feb. 2020). Each subject was asked to provide 1 mL of exhaled breath condensate (EBC). Data were analyzed using linear mixed-effects models. The results showed that PM 10 , PM 2.5 , O 3 , and PM 2.5 -bounded metals were negatively linked to Nrf2 expression level in EBC of females with -58.3% (95% CI: 79.5, -15.4), -32.1% (95% CI: -50.3, -7.1), -76.2% (95% CI: -92.6, -23.9), and -1.9 (95% CI: -3.4, -0.4), respectively. While our results presented no significant association between the studied pollutants and Nrf2 gene expression in males, significant associations were observed between the pollutants and total nitric oxide (NOx), interleukins 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the EBC of females. In the case of males, only EBC cytokines showed a significant association with air pollutants. Overall, this study suggests that exposure to ambient air pollutants may affect the respiratory system with biologically different mechanisms in males and females. PM 2.5 concentration had a positive correlation with exhaled TNF-α and IL6 values in females while positive correlation with TNF-α and negative correlation with IL6 values in males. O 3 had a negative correlation with TNF-α in males., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators. The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM., Methods: In total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis)., Results: Exposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0&#95;16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators., Conclusion: There were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways., Competing Interests: The corresponding author, A-CA and A-CO are shareholders of PEXA AB and A-CO is a board member. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Almstrand, Bredberg, Runström Eden, Karlsson, Assenhöj, Koca, Olin and Tinnerberg.)

Atmospheric bioaerosols contain live and dead biological components that can enter the human respiratory tract (HRT) and affect human health. Here, the total microorganisms in a coastal megacity, Qingdao, were characterized on the basis of long-term observations from October 2013 to January 2021. Particular attention was given to the size dependence of inhalable bioaerosols in concentration and respiratory deposition in different populations on foggy and hazy days. Bioaerosol samples stained with 4,6-diamidino-2-phenylindole (DAPI) were selected to measure the total airborne microbe (TAM) concentrations with an epifluorescence microscope, while a multiple-path particle dosimetry model was employed to calculate respiratory deposition. The mean TAM concentrations in the particle size range of 0.65-1.1 μm (TAM 0.65-1.1 ) were 1.23, 2.02, 1.60 and 2.33 times those on sunny reference days relative to the corresponding values on days with slight, mild, moderate and severe levels of haze, respectively. The mean concentration of TAMs in the particle size range of 0.65-2.1 μm (TAM 0.65-2.1 ) on severely hazy days was (2.02 ± 3.28) × 10 5  cells/m 3 , with a reduction of 4.16% relative to that on the reference days. The mean TAM 0.65-2.1 concentration changed from (1.50 ± 1.37) × 10 5  cells/m 3 to (1.76 ± 1.36) × 10 5  cells/m 3 , with TAM 0.65-1.1 increasing from (7.91 ± 7.97) × 10 4  cells/m 3 to (1.76 ± 1.33) × 10 5  cells/m 3 on days with light fog days and medium fog, respectively. The modeling results showed that the majority of TAM 0.65-2.1 deposition occurred in the extrathoracic (ET) region, followed by the alveolar (AL) region. When different populations were examined separately, the deposition doses (DDs) in adult females and in children ranked at the minimum value (6.19 × 10 3  cells/h) and maximum value (1.08 × 10 4  cells/h), respectively. However, the inhalation risks on polluted days, such as hazy, foggy and mixed hazy-foggy (HF) days, were still below the threshold for adverse impacts on human health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to the growing maker culture, maker spaces using multiple fused deposition modeling (FDM)-3D printers have spread around the world. However, the 3D printing process is known to cause the release of ultrafine and fine particles, which may have adverse health effects on occupants. Therefore, this experiment-based study was conducted on FDM-3D printers placed in an actual makerspace by the following three scenarios: the number of operating FDM-3D printers, ventilation, and measurement location to compare the concentrations of ultrafine and fine particles. In addition, the deposited dose in alveolar region for ultrafine and fine particles was predicted using a respiratory deposition model to analyze the potential health risk on occupants. As a result, the scenario-based comparison revealed that if the number of operating 3D printers is reduced by less than half, the potential health risk can be decreased by 34.1%, proper ventilation can reduce potential health risk by 55.5%, and working away from the 3D printer can also reduce potential health risk by up to 27.5%. This study analyzed the potential health risk of multiple FDM-3D printers on users in an actual makerspace, and proposed various improvement measures to reduce the potential health risk of ultrafine and fine particles., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment (Hachadorian et al., 2020). However, it is accompanied by risks because it seriously harms normal cells while killing cancer cells. The side effects can lower cancer patients' quality of life and are very unpredictable due to individual differences (Bentzen, 2006). Therefore, it is essential to assess a patient's body damage after radiotherapy to formulate an individualized recovery treatment plan. Exhaled volatile organic compounds (VOCs) can be changed by radiotherapy and thus used for medical diagnosis (Vaks et al., 2012). During treatment, high-energy X-rays can induce apoptosis; meanwhile, cell membranes are damaged due to lipid peroxidation, converting unsaturated fatty acids into volatile metabolites (Losada-Barreiro and Bravo-Díaz, 2017). At the same time, radiotherapy oxidizes water, resulting in reactive oxygen species (ROS) that can increase the epithelial permeability of pulmonary alveoli, enabling the respiratory system to exhale volatile metabolites (Davidovich et al., 2013; Popa et al., 2020). These exhaled VOCs can be used to monitor body damage caused by radiotherapy.

Between 2007 and 2012, hospitalization rate related to respiratory system diseases in children ≤1-year-old was near 7 times higher in Nunavik compared with the whole province of Quebec. To assess the impact of poor indoor air quality (IAQ) in residential environments on children's respiratory health, the Nunavik's intervention study investigated the impact of the optimization of ventilation systems on the incidence rates of respiratory infections in children in Nunavik. Children under 10 years were recruited and categorized according to the type of ventilation system in their home: energy recovery ventilator (ERV), heat recovery ventilator (HRV), no HRV or ERV, and control groups. Children's' medical records were analyzed over a period of 50 weeks pre- and post-intervention. Clinical diagnoses were classified into 4 categories: upper respiratory infections, lower respiratory infections, otitis media, and asthma. A decrease in respiratory infections episodes was observed in all groups following intervention with the highest impact observed for HRV systems (-53.0%). Decreases in the ERV group were not significant (-21,7%) possibly due to the presence of some volatile organic compound (such as propylene glycol) and inerrant experimental bias. Nevertheless, no significant association was found between health episodes incidence and household's behaviors or IAQ., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Airborne particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are significant contributors leading to many human health issues. Thus, this study was designed to perform chemical analysis and biological impact of airborne particulate matter 10 (PM 10 ) in the World heritage City of Kandy City in Sri Lanka. 12 priority PAHs and 34 metals, including 10 highly toxic HMs were quantified. The biological effects of organic extracts were assayed using an in vitro primary porcine airway epithelial cell culture model. Cytotoxicity, DNA damage, and gene expressions of selected inflammatory and cancer-related genes were also assessed. Results showed that the total PAHs ranged from 3.062 to 36.887 ng/m 3 . The metals were dominated by Na > Ca > Mg > Al > K > Fe > Ti, while a few toxic HMs were much higher in the air than the existing ambient air quality standards. In the bioassays, a significant cytotoxicity (p < 0.05) was observed at 300 μg/mL treatment, and significant (p < 0.05) DNA damages were noted in all treatment groups. All genes assessed were found to be significantly up-regulated (p < 0.05) after 24 h of exposure and after 48 h, only TGF-β1 and p53 did not significantly up-regulate (p < 0.05). These findings confirm that the Kandy city air contains potential carcinogenic and mutagenic compounds and thus, exposure to Kandy air may increase the health risks and respiratory tract-related anomalies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Disease-related effects on hepatic metabolism can alter the composition of chemicals in the circulation and subsequently in breath. The presence of disease related alterations in exhaled volatile organic compounds could therefore provide a basis for non-invasive biomarkers of hepatic disease. This study examined the feasibility of using global volatolomic profiles from breath analysis in combination with supervised machine learning to develop signature pattern-based biomarkers for cirrhosis. Breath samples were analyzed using thermal desorption-gas chromatography-field asymmetric ion mobility spectroscopy to generate breathomic profiles. A standardized collection protocol and analysis pipeline was used to collect samples from 35 persons with cirrhosis, 4 with non-cirrhotic portal hypertension, and 11 healthy participants. Molecular features of interest were identified to determine their ability to classify cirrhosis or portal hypertension. A molecular feature score was derived that increased with the stage of cirrhosis and had an AUC of 0.78 for detection. Chromatographic breath profiles were utilized to generate machine learning-based classifiers. Algorithmic models could discriminate presence or stage of cirrhosis with a sensitivity of 88-92% and specificity of 75%. These results demonstrate the feasibility of volatolomic profiling to classify clinical phenotypes using global breath output. These studies will pave the way for the development of non-invasive biomarkers of liver disease based on volatolomic signatures found in breath., Competing Interests: The authors have declared that no competing interests exist.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a global crisis. It is still unresolved. Although many therapies and vaccines are being studied, they are still in their infancy. As this pandemic continues, rapid and accurate research for the development of therapies and vaccines is needed. Therefore, it is necessary to understand characteristics of diseases caused by SARS-CoV-2 through animal models. Syrian hamsters are known to be susceptible to SARS-CoV-2. They were intranasally inoculated with SARS-CoV-2. At 2, 4, 8, 12, and 16 days post-infection (dpi), these hamsters were euthanized, and tissues were collected for ultrastructural and microstructural examinations. Microscopic lesions were prominent in the upper and lower respiratory tracts from 2 and 4 dpi groups, respectively. The respiratory epithelium in the trachea, bronchiole, and alveolar showed pathological changes. Inflammatory cells including neutrophils, lymphocytes, macrophages, and eosinophils were infiltrated in/around tracheal lamina propria, pulmonary vessels, alveoli, and bronchiole. In pulmonary lesions, alveolar wall was thickened with infiltrated inflammatory cells, mainly neutrophils and macrophages. In the trachea, epithelial damages started from 2 dpi and recovered from 8 dpi, consistent with microscopic results, High levels of SARS-CoV-2 nucleoprotein were detected at 2 dpi and 4 dpi. In the lung, lesions were most severe at 8 dpi. Meanwhile, high levels of SARS-CoV-2 were detected at 4 dpi. Electron microscopic examinations revealed cellular changes in the trachea epithelium and alveolar epithelium such as vacuolation, sparse micro-organelle, and poor cellular margin. In the trachea epithelium, the number of cytoplasmic organelles was diminished, and small vesicles were prominent from 2 dpi. Some of these electron-lucent vesicles were filled with virion particles. From 8 dpi, the trachea epithelium started to recover. Because of shrunken nucleus and swollen cytoplasm, the N/C ratio of type 2 pneumocyte decreased at 8 and 12 dpi. From 8 dpi, lamellar bodies on type 2 pneumocyte cytoplasm were increasingly observed. Their number then decreased from 16 dpi. However, there was no significant change in type 1 pneumocyte. Viral vesicles were only observed in the cytoplasm of type 2 pneumocyte. In conclusion, ultra- and micro-structural changes presented in this study may provide useful information for SARS-CoV-2 studies in various fields., (© 2021. The Author(s).)

Abstract: This work considers the implications of cloth masks due to the COVID-19 pandemic on suspected plutonium inhalations and dose assessment. In a plutonium inhalation scenario, the greater filtration efficiency for large particles exhibited by cloth masks can reduce early fecal excretion without a corresponding reduction in dose. For plutonium incidents in which cloth masks are worn, urinary excretion should be the preferred method of inferring dose immediately after the inhalation, and fecal excretion should be considered unreliable for up to 10 days., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Health Physics Society.)

Urban gardening has been experiencing increased popularity around the world. Many urban gardens are located on sites that may be contaminated by trace elements or organic compounds due to previous use. The three main exposure pathways to the human body for soil contaminants are (a) ingestion of soil directly, (b) consumption of produce containing or superficially contaminated with a contaminant, (c) and inhalation of soil dust. The first two modes have received much attention; however, the contribution of the inhalation route has not been investigated adequately. Two inhalation risk studies were carried out in urban gardens located in Kansas City, MO, by collecting dust while 25-m 2 plots were rototilled. Microclimatic variables were monitored, and total inhalable dust mass was determined using a personal sampling train including a small pump and air filter. Soil lead (Pb) concentration was assessed at both sites. For Study 1, particle size distribution of collected particles was estimated through analysis of scanning electron microscope images of filters. Little dust was collected at either site. Most particles captured, however, appeared to be <4 μm in diameter. The amount of dust emitted was correlated with soil moisture. Tilling reduced soil aggregate size and blended soil, resulting in a more homogeneous distribution of Pb. Dust inhalation while tilling is likely not a major Pb exposure risk for gardeners, but given the preponderance of very small particles in what was captured, care should be taken to prevent dust from entering the respiratory system., (© 2021 The Authors. Journal of Environmental Quality © 2021 American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Bacterial loading aggravates the health and environmental hazards of particulate matter (PM), particularly in concentrated animal feeding operations. Understanding the association between PM and airborne bacteria is conducive to accurately assessing occupational exposure, providing fundamental data for exposure mitigation via engineering solutions, and providing information regarding the physical properties influencing the transmission of airborne microorganisms at emission sources. In this work, we conducted a joint study to systematically determine the concentrations and size distributions of PM and airborne bacteria, and establish the quantitative relationship between PM and airborne bacteria in laying hen houses. The association between PM and airborne bacteria was expressed as the load of airborne bacteria on PM in terms of the identical particle size interval based on the size-resolved respiratory tract deposition. The concentrations and size distributions of PM and airborne bacteria in laying hen houses were affected by the in-house space (upper and lower), chicken activity (day and night), and outside temperature. The size distributions of PM and airborne bacteria indicated that the mass concentration of large particles decreased with increasing outside temperature, while the concentration of airborne bacteria loaded on the small particles increased with increasing outside temperature. The results indicated that particles with diameters ranging from 2.1 to 4.7 μm carried the most airborne bacteria. Therefore, particles with diameters ranging from 2.1 to 4.7 μm should be the focus of future experimental research on occupational exposure, air quality improvement, and the airborne transmission of PM and airborne microorganisms originating from concentrated layer feeding operations., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Effective evaluation and prediction of aerosol transport deposition in the human respiratory tracts are critical to aerosol drug delivery and evaluation of inhalation products. Establishment of an in vitro-in vivo correlation (IVIVC) requires the understanding of flow and aerosol behaviour and underlying mechanisms at the microscopic scale. The achievement of the aim can be facilitated via computational fluid dynamics (CFD) based in silico modelling which treats the aerosol delivery as a two-phase flow. CFD modelling research, in particular coupling with discrete phase model (DPM) and discrete element method (DEM) approaches, has been rapidly developed in the past two decades. This paper reviews the recent development in this area. The paper covers the following aspects: geometric models of the respiratory tract, CFD turbulence models for gas phase and its coupling with DPM/DEM for aerosols, and CFD investigation of the effects of key factors associated with geometric variations, flow and powder characteristics. The review showed that in silico study based on CFD models can effectively evaluate and predict aerosol deposition pattern in human respiratory tracts. The review concludes with recommendations on future research to improve in silico prediction to achieve better IVIVC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Abstract: Inhalation of plutonium is a significant contributor of occupational doses in plutonium production, nuclear fuel reprocessing, and cleanup operations. Accurate assessment of the residence time of plutonium in the lungs is important to properly characterize dose and, consequently, the risk from inhalation of plutonium aerosols. This paper discusses the long-term retention of plutonium in different parts of the respiratory tract of two workers who donated their bodies to the US Transuranium and Uranium Registries. The post-mortem tissue radiochemical analysis results, along with the urine bioassay data, were interpreted using Markov Chain Monte Carlo and the latest biokinetic models presented in the Occupational Intakes of Radionuclides series of ICRP publications. The materials inhaled by both workers were found to have solubility between that of plutonium nitrates and oxides. The long-term solubility was also confirmed by comparison of the activity concentration in the lungs and the thoracic lymph nodes. The data from the two individuals can be explained by assuming a bound fraction (fraction of plutonium deposited in the respiratory tract that becomes bound to lung tissue after dissolution) of 1% and 4%, respectively, without having to significantly alter the particle clearance parameters. Effects of different assumptions about the bound fraction on radiation doses to different target regions was also investigated. For inhalation of soluble materials, an assumption of fb of 1%, compared to the ICRP default of 0.2%, increases the dose to the most sensitive target region of the respiratory tract by 258% and that to the total lung by 116%. Some possible alternate methods of explaining higher-than-expected long-term retention of plutonium in the upper respiratory tract of these individuals-such as physical sequestration of material into the scar tissues and possible uptake by lungs-are also briefly discussed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Health Physics Society.)

Rationale: The aim of this work is to use a new design of online sampling photoionization mass spectrometer to analyze chemical ingredients in inhaled and exhaled cigarette smoke directly without separation., Methods: Based on vacuum ultraviolet photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS) and a sampling system, a newly developed rapid online sampling design approach was used for the upper respiratory tract retention study of gaseous mainstream cigarette smoke components during smoking. The cigarette smoke inhaled or exhaled by seven subjects who displayed three different smoking patterns was directly sampled into a vacuum chamber, photoionized, and analyzed using TOFMS., Results: Fourteen species, comprising aldehydes, ketones, phenol, methanethiol, nitrogen-containing heterocyclic compounds and unsaturated hydrocarbons, were identified in the cigarette smoke obtained from Virginia-type cigarettes. The upper respiratory tract results for these compounds were similar for smokers with the three different smoking patterns: aldehyde and ketone constituents had a high retention level of more than 60%; phenol, methanethiol, and nitrogen-containing heterocyclic compounds were retained at between 30% and 70%; and the retention of unsaturated hydrocarbons was about 20%-60%. The retention trend of the same smoke components in Virginia-type cigarettes by subjects from the three smoking patterns (A, B, and C) was consistent, and the retentions all increased with increased smoking age (A < B < C)., Conclusions: This is the first report of a new online sampling design approach to the study of cigarette smoke components in inhaled and exhaled breath, to evaluate components retained in the upper respiratory tract by subjects with different smoking patterns. This method has good repeatability, and the results indicated that this is a very promising tool for the study of the retention of cigarette smoke constituents., (© 2020 John Wiley & Sons Ltd.)

In the present study, we evaluated the effects of chronic exposure to traffic from a heavy-duty diesel-fueled vehicle area on respiratory symptoms and airway inflammation in a nonsmoking adult and elderly population. Respiratory symptoms were evaluated by the ISAAC questionnaire (International Study of Asthma and Allergies questionnaire), and airway inflammation was assessed by fractional exhaled nitric oxide (FeNO). Forty volunteers were selected from the 112 volunteers who completed the ISAAC questionnaire for the measurement of FeNO. The FeNO population comprised seven men (six aged ≥ 64 years old, four aged ≥ 75 years old) and 32 women (27 aged ≥ 64 years old, nine aged ≥ 75 years old). FeNO levels were tracked for six months, from November 2014 to June 2015. Results: Twenty-four percent of the volunteers reported having had wheezing in the chest in the last 12 months. However, only 2.7% of the volunteers reported doctor-diagnosed asthma. There was a positive association between FeNO and pollutants in most of the study months. An increase of 1 μg m -3 in NO 2 was associated with a mean increase of 1.08 ppb in FeNO, and an increase of 1 μg m -3 in O 3 was associated with a mean increase of 1.06 ppb in FeNO. The relative risk for NO 2 ranged from 1.009 to 1.32 and that for O 3 ranged from 1.014 to 1.020. Conclusion: The frequency of respiratory symptoms was much higher than the previously described levels of 6% in the Brazilian adult population. In summary, a high frequency of respiratory symptoms and high levels of FeNO were described in an underdiagnosed adult population living very close to a heavy-duty diesel-traffic area. Older elderly adults presented greater susceptibility to airway inflammation than younger adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A critical element of the risk assessment of exposure to airborne ambient ultrafine particles (UFP) is the quantification of respiratory tract deposition (RTD) of the particles, which is intrinsically challenging, particularly at the population scale. In this study, we used a recently proposed method to experimentally determine the RTD of urban UFP in a large group of children exposed to these particles in a school setting in Brisbane, Australia. Children are one of the most susceptible population groups; However, little is known about the deposition of UFP from urban traffic in their airways. In order to advance the knowledge in this field, the objectives of this study were: to determine the deposition of ambient urbane UFP in large number children, to catergorize the source of inhaled UFPs and hence to assess the contribution of air pollution sources to the deposition. RTD was measured in children aged 8-11 at primary schools using a flow-through chamber bag system. First, the inhaled and exhaled air was separated; then the particle number size distribution and particle number concentration were measured. The sources of inhaled UFP were categorized according to their particle number size distribution by a K means cluster technique. A total of 128 children from five schools performed the RTD measurement. The mean total deposition fraction of urban UFP in all children was 0.59 ± 0.10. Inhaled UFP were categorized into two groups: traffic and urban background, with the GMD of corresponding particle number size distribution of 20 nm and 40 nm, respectively. The total deposition fraction (mean ± SD) of UFP from these two groups was 0.68 ± 0.09 for traffic and 0.55 ± 0.08 for urban background respectively. This is the first study in which RTD was measured in a large group of children inhaling real urban UFP. First, we proved that this novel method can indeed be applied easily and quickly to a large group of people. Second, we quantified the RTD of children, thus providing an important input to the risk assessment for exposure to UFP., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epidemiological studies have shown an increased respiratory morbidity and mortality as a consequence of exposure to air pollution. Short term exposure to air pollution is associated with an increased respiratory mortality and exacerbation of respiratory symptoms. Long term exposure to air pollution is associated with a progressive lung function decline as well as the development of chronic pulmonary diseases. In this article, we analyze the impact of major atmospheric pollutants on respiratory health and its impact on COPD, asthma and lung cancer. This review explores the impact of household air pollution on respiratory health as well as the relationship between ambient atmospheric air pollution and physical activity., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Aerosol samples were collected using eight stage non-viable Andersen cascade impactor at three urban and two rural sites in north-east India during 2018 covering three seasons i.e., winter, summer and monsoon. The size-segregated samples collected in the selected locations were carefully analysed in terms of deposition in human respiratory tract using inhalation and deposition curves. Seasonal variation of fractional deposition of particulate matter (PM) in human respiratory tract was observed. For example, during winter, in one of the urban sites i.e., S3 (0.61) the maximum deposition was in Pulmonary (P) region, while in the case of other sites, the maximum deposition was in Nasopharyngeal (NOPL) region. Regional deposition in P was high in S1 and S3 when compared with other sites. Vehicular emissions was dominant in both S1 and S3 in P, while biomass burning being dominant in S3 which could be the reason for maximum deposition in P. Positive matrix factorization (PMF) revealed five to eight factors at each individual site in NOPL, tracheobronchial (TB) and P regions: biomass burning (accounting for 7-32% of PM), coal combustion (14-27%), construction dust (9-25%), dust emissions (17-28%), industrial emissions (12-26%), oil refinery (18%), secondary aerosols (17-33%) and vehicular emissions (12-39%). Dominant sources in urban and rural areas were vehicular emissions and dust emissions, respectively. Therefore, the present study highlights the importance of analyzing source apportionment of PM at ultrafine scale and forms a basis upon which the future air quality studies and mitigation strategies can be formulated in this region., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Particles emitted from five typical types of vehicles (including light-duty gasoline vehicles, LDG; heavy-duty gasoline vehicles, HDG; diesel buses, BUS; light-duty diesel vehicles, LDD and heavy-duty diesel vehicles, HDD) were collected with a dilution sampling system and an electrical low-pressure impactor (ELPI+, with particle sizes covering fourteen stages from 6 nm to 10 μm) on dynamometer benches. The mass concentrations and emission factors (EF) for organic carbon (OC) and elemental carbon (EC) were obtained with a DRI Model 2001 thermal/optical carbon analyzer. A respiratory deposition model was used to calculate the deposition fluxes of size-segregated carbonaceous aerosols in human respiratory system. Results indicated that the OC produced from LDG mainly existed in the size range of 2.5-10 μm, while EC from HDG enriched in 0.94-2.5 μm. For diesel vehicles, both OC and EC concentrations peaked at 0.094-0.25 μm. The OC/EC ratios for PM 2.5 varied from different types of vehicles, from 0.61 to 8.35. The primary emissions from LDD and HDD exhibited high OC/EC ratios (>3), suggesting that using OC/EC higher than 2 to indicate the formation of secondary organic aerosol (SOA) was not universal. The emission factors for OC and EC of LDG (HDG) in PM 10 were 1.78 (3.14) mg km -1 and 0.88 (4.32) mg km -1 , respectively. The OC2 and OC3 were the main section (over 60%) of OC emitted from all the five types of vehicles. EC1 was the most abundant EC fraction of LDG (76.9%), while EC2 dominated for other types of vehicles (more than 62%). About 60% of the OC in ultrafine particles could be deposited in the alveoli. Diesel EC mainly could be deposited in the alveolar region. It is necessary to control the emission of ultrafine particles and diesel EC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In the framework of the 2017 "carbonaceous aerosol in Rome and Environs" (CARE) experiment, particle number size distributions have been continuously measured on February 2017 in downtown Rome. These data have been used to estimate, through MPPD model, size and time resolved particle mass, surface area and number doses deposited into the respiratory system. Dosimetry estimates are presented for PM 10 , PM 2.5 , PM 1 and Ultrafine Particles (UFPs), in relation to the aerosol sources peculiar to the Mediterranean basin and to the atmospheric conditions. Particular emphasis is focused on UFPs and their fraction deposited on the olfactory bulb, in view of their possible translocation to the brain. The site of PM 10 deposition within the respiratory system considerably changes, depending on the aerosol sources and then on its different size distributions. On making associations between health endpoints and aerosol mass concentrations, the relevant coarse and fine fractions would be more properly adopted, because they have different sources, different capability of penetrating deep into the respiratory system and different toxicological implications. The separation between them should be set at 1 µm, rather than at 2.5 µm, because the fine fraction is considerably less affected by the contribution of the natural sources. Mass dose is a suitable metric to describe coarse aerosol events but gives a poor representation of combustion aerosol. This fraction of particles, made of UFPs and of accumulation mode particles (mainly with size below 0.2 µm), is of high health relevance. It elicited the highest oxidative activity in the CARE experiment and is properly described by the particle surface area and by the number metrics. Such metrics are even more relevant for the UFP doses deposited on the olfactory bulb, in consideration of the role recognized to oxidative stress in the progression of neurodegenerative diseases. Such metrics would be more appropriate, rather than PM x mass concentrations, to correlate neurodegenerative pathologies with aerosol pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Water, the major body fluid in humans, has four main naturally occurring isotopologues, H 2 16 O, H 2 17 O, H 2 18 O, and H 2 H 16 O (i.e., HD 16 O) with different masses. The underlying mechanisms of the isotope-specific water-metabolism in the human gastrointestinal (GI) tract and respiratory system are largely unknown and remained illusive for several decades. Here, a new strategy has been demonstrated that provides direct quantitative experimental evidence of triple-isotopic signatures of water-metabolism in the human body in response to the individual's water intake habit. The distribution of water isotopes has been monitored in drinking water (DW; δD = -36.59 ± 10.64‰ (SD), δ 18 O = -5.41 ± 1.47‰ (SD), and δ 17 O = -2.92 ± 0.79‰ (SD)), GI fluid (GF; δD = -35.91 ± 7.30‰ (SD), δ 18 O = -3.98 ± 1.29‰ (SD), and δ 17 O = -2.37 ± 0.57‰ (SD)), and human exhaled breath (EB; δD = -119.63 ± 7.27‰ (SD), δ 18 O = -13.69 ± 1.23‰ (SD), and δ 17 O = -8.77 ± 0.98‰ (SD)) using a laser-based off-axis integrated cavity output spectroscopy (OA-ICOS) technique. This study explored a new analytical method to disentangle the competing effects of isotopic fractionations of water during respiration in humans. In addition, our findings revealed that deuterium-enriched exhaled semiheavy water, i.e., HD 16 O is a new marker of the noninvasive assessment of the ulcer-causing H. pylori gastric pathogen. We also clearly showed that the water-metabolism-derived triple-isotopic compositions due to impaired water absorption in the GI tract can be used as unique tracers to track the onset of various GI dysfunctions. These findings are thus bringing a new analytical methodology to better understand the isotope-selective water-metabolism that will have enormous applications for clinical testing purposes.

E-cigarette use is dramatically increasing, particularly with adolescents. While the chemical composition of e-liquids and e-vapor is well characterized, the particle size distribution and the human airways deposition patterns of e-cigarette particles are understudied and poorly understood despite their likely contribution to adverse health effects from e-cigarette usage. In this study, we examined the impacts of e-cigarette device power, e-liquid composition, and vaping topography on e-cigarette particle sizes and their deposition in human airways. In addition, we observed that particle measurement conditions (dilution ratio, temperature, and humidity) significantly affect measured e-cigarette particle sizes. E-cigarette power output significantly increased particle count median diameters (CMD) from 174 ± 13 (particles generated under 6.4 W) to 236 ± 14 nm (particles generated under 31.1 W). E-cigarette particles generated from propylene glycol-based e-liquids (CMD = 145 ± 8 nm and mass median diameter [MMD] = 3.06 ± 0.17 μm) were smaller than those generated from vegetable glycerin-based e-liquids (CMD = 182 ± 9 nm and MMD = 3.37 ± 0.21 μm). Puff volume also impacted vapor particle size: CMD and MMD were 154 ± 11 nm and 3.50 ± 0.27 μm, 163 ± 6 nm and 3.35 ± 0.24 μm, and 146 ± 12 nm and 2.95 ± 0.14 μm, respectively, for 35, 90, and 170 mL puffs. Estimated e-cigarette particle mass deposition fractions in tracheobronchial and bronchoalveolar regions were 0.504-0.541 and 0.073-0.306, respectively. Interestingly, e-cigarette particles are smaller than the particles generated from cigarette smoking but have similar human airway deposition patterns.

Introduction: Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways containing, for example, Surfactant protein A (SP-A) and albumin, potential biomarkers of small airway disease. We hypothesized that there are differences between morning, noon, and afternoon measurements and that the variability of repeated measurements is larger between days than within days., Methods: PEx was obtained in sixteen healthy non-smoking adults on 11 occasions, within one day and between days. SP-A and albumin were quantified by ELISA. The coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were used to assess the variation of repeated measurements., Results: SP-A and albumin increased significantly from morning towards the noon and afternoon by 13% and 25% on average, respectively, whereas PEx number concentration and particle mean mass did not differ significantly between the morning, noon and afternoon. Between-day CRs were not larger than within-day CRs., Conclusions: Time of the day influences the contents of SP-A and albumin in exhaled particles. The variation of repeated measurements was rather high but was not influenced by the time intervals between measurements., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Björn Bake, Marianne Andersson and Gunilla Runström Eden are shareholders of PEXA® AB (www.PEXA.se) and Anna-Carin Olin is a board member (patent WO2009045163). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Flow cytometry is one of the most widely used techniques for the detection of surface markers on various cells, particularly the cells of the immune system, at a single-cell resolution. Modern flow cytometers can identify rare cell population in highly heterogeneous samples. Here we present a protocol that allows a precise detection of basophils as well as eosinophils and neutrophils in induced sputum samples. The identification of sputum basophils and other granulocytes contributes to a better understanding of the cellular network that promotes and regulates inflammation of the lower respiratory tract.

Background: Smoking leads to the aging of organs. However, no studies have been conducted to quantify the effect of smoking on the aging of respiratory organs and the aging-reversing ability of smoking cessation., Results: We collected genome-wide methylation datasets of buccal cells, airway cells, esophagus tissue, and lung tissue from non-smokers, smokers, and ex-smokers. We used the "epigenetic clock" method to quantify the epigenetic age acceleration in the four organs. The statistical analyses showed the following: (1) Smoking increased the epigenetic age of airway cells by an average of 4.9 years and lung tissue by 4.3 years. (2) After smoking ceased, the epigenetic age acceleration in airway cells (but not in lung tissue) slowed to a level that non-smokers had. (3) The epigenetic age acceleration in airway cells and lung tissue showed no gender difference., Conclusions: Smoking can accelerate the epigenetic age of human respiratory organs, but the effect varies among organs and can be reversed by smoking cessation. Our study provides a powerful incentive to reduce tobacco consumption autonomously.

Human exposure to volatile organic compounds (VOCs) via inhalation might increase the risk of specific diseases. Human breath has been widely investigated as a source of VOCs. However, the role of the human respiratory system as a sink for VOCs is much less studied. In this observational study, the VOC concentrations in inhaled and exhaled air in different environmental conditions were investigated. A total of 98 healthy non-smoking subjects who were exposed to a wide variation in levels of VOCs participated in this study. Individual and statistical results show that human breath could serve as a source for some VOCs and a sink for others, and even when human breath serves as a sink, not all VOCs were 100% absorbed. Interestingly, an increase in inhaled concentrations of toluene was observed to convert human breath from being a source to being a sink. Attention could be given to those VOCs for which humans act as a strong sink., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Depending on their concentrations, sizes, and types, particulate matters of biological origins (bioPM) significantly affect human health. However, for different air environments, they are not well characterized and can vary considerably. As an example, we investigated the bioPM differences at an urban (Beijing) site and a rural (Wangdu) site in the North China Plain (NCP) using an online monitoring instrument, an ultraviolet aerodynamic particle sizer (UV-APS), the limulus amebocyte lysate (LAL) assay, and a high-throughput sequencing method. Generally, lower concentrations of viable bioPM (hourly mean: 1.3 × 10 3  ± 1.6 × 10 3  m -3 ) and endotoxin (0.66 ± 0.16 EU/m 3 ) in Beijing were observed compared to viable bioPM (0.79 × 10 5  ± 1.4 × 10 5  m -3 ) and endotoxin (15.1 ± 23.96 EU/m 3 ) at the Wangdu site. The percentage of viable bioPM number concentration in the total PM was 3.1% in Beijing and 6.4% in Wangdu. Approximately 80% of viable bioPM was found to be in the range from 1 to 2.5 μm. Nevertheless, the size distribution patterns for viable bioPM at the Beijing and Wangdu sites differed and were affected by PM pollution, leading to distinct lung deposition profiles. Moreover, the distinct diurnal variations in viable bioPM on clean days were dimmed by the PM pollution at both sites. Distinct bacterial community structures were found in the air from the Beijing and Wangdu sites. The bacterial community in urban Beijing was dominated by genus Lactococcus (49.5%) and Pseudomonas (15.1%), while the rural Wangdu site was dominated by Enterococcus (65%) and Paenibacillus (10%). Human-derived genera, including Myroides, Streptococcus, Propionibacterium, Dietzia, Helcococcus, and Facklamia, were higher in Beijing, suggesting bacterial emission from humans in the urban air environment. Our results show that different air harbors different biological species, and people residing in different environments thus could have very different biological particle exposure., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cleaning workers are exposed to many risk factors, including handling of cleaning products. Epidemiological studies show that they have a high incidence of asthma and other respiratory symptoms. Some studies have indicated an even higher incidence of asthma in individuals using cleaning sprays regularly. It is known that sprays produce an aerosol that can expose the respiratory system to chemicals. Knowledge of the physical characteristics of the airborne particles, as well as the characteristics of the gas phase, is needed to determine how they affect the respiratory tract and why they cause airway symptoms. The aim of this study was to characterize the aerosols from seven different ready-to-use trigger cleaning sprays in terms of total airborne mass fraction, particle size distribution, and new particle formation from ozone reactions. An additional aim was to calculate the respiratory deposition fraction of the measured particles. The total airborne mass fraction was determined by comparing the mass deposited on the chamber wall with the mass emitted from the bottle during spraying. Particle number concentration and size distribution of the airborne particles were measured using an aerodynamic particle sizer and a fast aerosol mobility size spectrometer. The total airborne mass fraction was between 2.7% and 32.2% of the mass emitted from the bottle, depending on the product. Between 0.0001% and 0.01% of the total airborne mass fraction consisted of residual particles. However, these particles had a mass median aerodynamic diameter between 1.9 µm and 3.7 µm, constituting a total respiratory deposition of up to 77%. New particle formation in the presence of ozone was also shown to vary between 5,000 cm -3 and 35,000 cm -3 depending on the product, in the studied settings. These findings confirm that a substantial part (up to 1/3) of the mass sprayed from the bottle does not reach the intended surface. Thus, the use of cleaning sprays can result in chemical airway exposure, with particles in the relevant size range for both nasal and alveolar deposition.

The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. These enzymes ensure either the capture or the glutathione conjugation of a large number of ligands. Using a multi-technique approach (proteomic, immunocytochemistry and activity assays), our results indicate that GSTs play an important role in the rat olfactory process. First, proteomic analysis demonstrated the presence of different putative odorant metabolizing enzymes, including different GSTs, in the rat nasal mucus. Second, GST expression was investigated in situ in rat olfactory tissues using immunohistochemical methods. Third, the activity of the main GST (GSTM2) odorant was studied with in vitro experiments. Recombinant GSTM2 was used to screen a set of odorants and characterize the nature of its interaction with the odorants. Our results support a significant role of GSTs in the modulation of odorant availability for receptors in the peripheral olfactory process., Competing Interests: The authors have declared that no competing interests exist.

In this study, we present the development of a mobile system to measure real-world total respiratory tract deposition of inhaled ambient black carbon (BC). Such information can be used to supplement the existing knowledge on air pollution-related health effects, especially in the regions where the use of standard methods and intricate instrumentation is limited. The study is divided in two parts. Firstly, we present the design of portable system and methodology to evaluate the exhaled air BC content. We demonstrate that under real-world conditions, the proposed system exhibit negligible particle losses, and can additionally be used to determine the minute ventilation. Secondly, exemplary experimental data from the system is presented. A feasibility study was conducted in the city of La Paz, Bolivia. In a pilot experiment, we found that the cumulative total respiratory tract deposition dose over 1-h commuting trip would result in approximately 2.6 μg of BC. This is up to 5 times lower than the values obtained from conjectural approach (e.g. using physical parameters from previously reported worksheets). Measured total respiratory tract deposited BC fraction varied from 39% to 48% during walking and commuting inside a micro-bus, respectively. To the best of our knowledge, no studies focusing on experimental determination of real-world deposition dose of BC have been performed in developing regions. This can be especially important because the BC mass concentration is significant and determines a large fraction of particle mass concentration. In this work, we propose a potential method, recommendations, as well as the limitations in establishing an easy and relatively cheap way to estimate the respiratory tract deposition of BC., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Exhaled breath condensate (EBC) analysis is a noninvasive method to assess the lower respiratory tract. In human subjects, EBC hydrogen peroxide (H 2 O 2 ), pH and leukotriene B 4 (LTB 4 ) are useful for detection and monitoring of inflammatory lung diseases, including asthma., Objectives: To determine associations between EBC biomarkers and cytological and endoscopic definitions of lower airway inflammation (LAI) while controlling for sampling and environmental variables., Study Design: Prospective, cross-sectional study., Methods: Clinical, endoscopic and airway cytological findings from 47 horses were compared with EBC pH and concentrations of H 2 O 2 and LTB 4 by univariate and multivariable analyses. Dichotomous (presence/absence of airway inflammation) and continuous outcome variables (differential cell counts in tracheal aspirate and bronchoalveolar lavage fluid, BALF) were evaluated and potential effects of collection and methodological factors were included., Results: EBC pH and H 2 O 2 concentrations were higher in horses with LAI and both were positively associated with the percentage of neutrophils in BALF (P<0.05). Mast cell percentage in BALF was negatively associated with EBC pH, and BALF eosinophil percentage was positively associated with EBC LTB 4 (P<0.05). Ambient temperature, relative humidity and assay methodology significantly impacted some analytes., Main Limitations: LAI is challenging to categorise due to a variety of clinical and cytological phenotypes. Although the study was designed to overcome this limitation, numbers of horses were small in some categories., Conclusions: EBC pH and H 2 O 2 concentrations are altered by airway inflammation, suggesting a role for these biomarkers in the diagnosis and monitoring of airway disease. Environmental and methodological factors can influence these biomarkers and should be considered in the interpretation of results., (© 2018 EVJ Ltd.)

Dry powder inhalation (DPI) has attracted much attention as a treatment for respiratory diseases owing to the large effective absorption area in a human respiratory system. Understanding the drug particle motion in the respiratory system and the deposition behavior is necessary to improve the efficiency of DPI. We conducted computer simulations using a model coupling a discrete element method and a computational fluid dynamics method (DEM-CFD) to evaluate the particle deposition in human respiratory system. A simple artificial respiratory model was developed, which numerically investigated the effect of particle properties and inhalation patterns on the particle deposition behavior. The DEM-CFD simulations demonstrated that the smaller- and lower-density particles showed higher reachability into the simple respiratory model, and the particle arrival ratio to the deep region strongly depended on the aerodynamic diameter. The particle arrival ratio can be described as an exponential function of the aerodynamic diameter. Furthermore, the exponential relationship between the particle reachability into the depth of the simple respiratory model and the aerodynamic diameter predicted the particle aerodynamic diameter based on the required reachability. The particle shape also had an impact on the particle deposition behavior. The rod-like particles with a larger aspect ratio indicated higher reachability into the depth of the simple respiratory model. This was attributed to the high velocity motion of the particles whose long axis was in the direction of the deep region.

The aim of this study was to investigate the expression patterns of miRNA-let 7a, 7b, and 7c in bronchoalveolar lavage fluid in infants with asthma and airway foreign bodies. Between January 2016 and February 2017, 27 infants were included and divided into observation group (infants with asthma, n = 15) and control group (infants with airway foreign bodies, n = 12). The differential expression profiles of miRNA-let 7a, 7b, and 7c were determined by reverse transcription-polymerase chain reaction in bronchoalveolar lavage fluid (BALF) from infants of the 2 groups. The BALF was collected from infants undergoing flexible bronchoscopy. MiRNA-let 7a, 7b, and 7c increased significantly in infants from observation group as compared with control group (2.72 ± 0.48 vs 1, 8.23 ± 1.64 vs 1, 3.16 ± 0.62 vs 1, respectively). The increased expression of miRNA-let 7a, 7b, and 7c were associated with the asthma of infants.

Bacteria need nutrients from the host environment to survive, yet we know little about which biochemicals are present in the airways (the metabolome), which of these biochemicals are essential for bacterial growth and how they change with airway disease. The aims of this pilot study were to develop and compare methodologies for sampling the upper and lower airway metabolomes and to identify biochemicals present in the airways that could potentially support bacterial growth. Eight healthy human volunteers were sampled by four methods: two standard approaches - nasal lavage and induced sputum, and two using a novel platform, synthetic adsorptive matrix (SAM) strips-nasosorption and bronchosorption. Collected samples were analyzed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Five hundred and eighty-one biochemicals were recovered from the airways belonging to a range of metabolomic super-pathways. We observed significant differences between the sampling approaches. Significantly more biochemicals were recovered when SAM strips were used, compared to standard sampling techniques. A range of biochemicals that could support bacterial growth were detected in the different samples. This work demonstrates for the first time that SAM strips are a highly effective method for sampling the airway metabolome. This work will assist further studies to understand how changes in the airway metabolome affect bacterial infection in patients with underlying airway disease.

Airborne fine particulate matter (PM 2.5 ) attracts more and more attention due to its environmental effects. The immune system appears to be a most sensitive target organ for the environmental pollutants. Inhaled PM 2.5 can deposit in different compartments in the respiratory tract and interact with epithelial cells and resident immune cells. Exposed to PM 2.5 can induce local or systematic inflammatory responses. This review focus on the effects of respiratory tract exposed to PM 2.5 . Firstly, we introduced the major emission sources, basic characteristics of PM 2.5 and discussed its immunoadjuvant potential. Secondly, we elaborated the immune cells in the respiratory tract and the deposition of PM 2.5 regarding the structural characteristics of the respiratory tract. Furthermore, we summarized the in vivo/vitro studies that revealed the immunotoxic effects of PM 2.5 exposure to pulmonary cellular effectors and explored the contribution of PM 2.5 exposure to the Th1/Th2 balance., (Copyright © 2018. Published by Elsevier B.V.)

The adverse respiratory health effects of PM 2.5 have been studied. However, the epidemiological evidence for the association of specific PM 2.5 sources with health outcomes is still limited. This study investigated the association between PM 2.5 components and sources with a biomarker of acute respiratory inflammation (FeNO) in guards. Personal exposure was estimated by microenvironment samplers and FeNO measurements were carried out before, during and after the Victory Day Military Parade in Beijing. Four sources were determined by factor analysis, including urban pollution, dust, alloy steel abrasion and toxic metals. A mixed-effect model was used to estimate the associations of FeNO with PM 2.5 sources and chemical constituents, controlling for age, BMI, smoke activity, physical activity, waist circumference, temperature and relative humidity. In summary, large concentration decreases in PM 2.5 concentration and PM 2.5 chemical constituents were observed in both roadside and indoor environments during the air control periods, immediately followed by statistically significant decreases in FeNO of roadside guards and patrol guards. Besides, statistically significant increases in FeNO were found to be associated with interquartile range (IQR) increases in some pollutants, with an increase of 1.45ppb (95% CI: 0.69, 2.20), 0.65ppb (95% CI: 0.13, 1.17), 1.48ppb (95% CI: 0.60, 2.35), 0.82ppb (95% CI: 0.44, 1.20), 0.77ppb (95% CI: 0.42, 1.11) in FeNO for mass, sulfate, BC, Ca 2+ and Sm, respectively. In addition, compared to alloy steel abrasion and toxic metals, urban pollution and dust factors were more associated with acute airway inflammation for highly-exposed populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Semi-volatile organic compounds (SVOCs) present in indoor environments are known to cause adverse health effects through multiple routes of exposure. To assess the aggregate exposure, the bioaccessibility and bioavailability of SVOCs need to be determined. In this review, we discussed measurements of the bioaccessibility and bioavailability of SVOCs after inhalation. Published literature related to this issue is available for 2,3,7,8-tetrachlorodibenzo-p-dioxin and a few polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and phenanthrene. Then, we reviewed common modeling approaches for the characterization of the gas- and particle-phase partitioning of SVOCs during inhalation. The models are based on mass transfer mechanisms as well as the structure of the respiratory system, using common computational techniques, such as computational fluid dynamics. However, the existing models are restricted to special conditions and cannot predict SVOC bioaccessibility and bioavailability in the whole respiratory system. The present review notes two main challenges for the estimation of SVOC bioaccessibility and bioavailability via inhalation in humans. First, in vitro and in vivo methods need to be developed and validated for a wide range of SVOCs. The in vitro methods should be validated with in vivo tests to evaluate human exposures to SVOCs in airborne particles. Second, modeling approaches for SVOCs need to consider the whole respiratory system. Alterations of the respiratory cycle period and human biological variability may be considered in future studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane receptor that binds chitin and other acetylated compounds with high affinity. FIBCD1 has previously been shown to be present in the epithelium of the gastrointestinal tract. In the present study, we performed a detailed analysis of normally structured human tissues for the expression of FIBCD1 by quantitative PCR and immunohistochemistry. We find that FIBCD1 is expressed in epithelial cells derived from all three germ layers. Endodermal-derived epithelial cells throughout the gastrointestinal tract and the respiratory system showed high expression of FIBCD1 and also mesodermal-derived cells in the genitourinary system and ectodermal-derived epidermis and sebaceous glands cells expressed FIBCD1. In some columnar epithelial cells, for example, in the salivary gland and gall bladder, the FIBCD1 expression was clearly polarized with strong apical reaction, while other columnar cells, for example, in small and large intestine and in bronchi, the staining was equally strong apically and basolaterally. In keratinocytes in skin, tongue, and oral cavity, the FIBCD1 staining was granular. This expression pattern together with the known binding properties supports that FIBCD1 plays a role in innate immunity in the skin and at mucosal surfaces.

Background: Inhaled tobramycin is important in the treatment of Pseudomonas aeruginosa (Pa) infections in cystic fibrosis (CF). However, despite its use it fails to attenuate the clinical progression of CF lung disease. The bactericidal efficacy of tobramycin is known to be concentration-dependent and hence changing the dosing regimen from a twice-daily (q12h) inhalation to a once-daily (q24h) inhaled double dose could improve treatment outcomes., Objectives: To predict local concentrations of nebulized tobramycin in the airways of patients with CF, delivered with the small airway-targeting Akita® system or standard PARI-LC® Plus system, with different inspiratory flow profiles., Methods: Computational fluid dynamic (CFD) methods were applied to patient-specific airway models reconstructed from chest CT scans. The following q12h and q24h dosing regimens were evaluated: Akita® (150 and 300 mg) and PARI-LC® Plus (300 and 600 mg). Site-specific concentrations were calculated., Results: Twelve CT scans from patients aged 12-17 years (median = 15.7) were selected. Small airway concentrations were 762-2999 mg/L for the q12h dosing regimen and 1523-5997 mg/L for the q24h dosing regimen, well above the MIC for WT Pa strains. Importantly, the q24h regimen appeared to be more suitable than the q12h regimen against more resistant Pa strains and the inhibitory effects of sputum on tobramycin activity., Conclusions: CFD modelling showed that high concentrations of inhaled tobramycin are indeed delivered to the airways, with the Akita® system being twice as efficient as the PARI-LC® system. Ultimately, the q24h dosing regimen appears more effective against subpopulations with high MICs (i.e. more resistant strains)., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract., Objectives: We evaluated a novel RSV fusion inhibitor, MDT-637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans., Method: MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations., Results and Conclusions: The IC 50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50 s. We also measured MDT-637 IC 50 s in 3 lab strains and 4 clinical strains. The IC 50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC 50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis., Methods: We characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronic-bronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort., Results: Mean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 μg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 μg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort., Conclusions: Airway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.).

This paper presents KDEP, an open-source implementation of the ICRP lung deposition model developed by the authors. KDEP, which is freely available to the public, can be used to calculate lung deposition values under a variety of different conditions using the ICRP methodology. The paper describes how KDEP implements this model and discusses some key points of the implementation. The published lung deposition values for intakes by workers were reproduced, and new deposition values were calculated for intakes by members of the public. KDEP can be obtained for free at github.com or by emailing the authors directly.