Change of Composition, Source Contribution, and Oxidative Effects of Environmental PM2.5 in the Respiratory Tract.

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 PM2.5 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 PM2.5 reaching the lung different from environmental PM2.5. 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 PM2.5 during the inhalation process and consequently make source contribution profiles for respiratory tract-deposited PM2.5 different from that for environmental PM2.5 as suggested in 11 Chinese cities and 12 US cities. We also observed that oxidative potential, one of the main health risk causes of PM2.5, increases by 41% after PM2.5 travels through the respiratory tract model. Our results reveal that PM2.5 inhaled in the lung differs from environmental PM2.5. This work provides a starting point for more health-oriented source apportionment, physiology-based health evaluation, and cost-effective control of PM2.5 pollution.

Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.

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.

Analysis of ways to reduce potential health risk from ultrafine and fine particles emitted from 3D printers in the makerspace.

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.

Impact of improved indoor air quality in Nunavik homes on children's respiratory health.

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.

Ultra- and micro-structural changes of respiratory tracts in SARS-CoV-2 infected Syrian hamsters.

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.

Fast analysis of selected compounds in inhaled and exhaled vapor phase of cigarette smoke to evaluate components retained in the upper respiratory tract.

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.

Airway Mucin Concentration as a Marker of Chronic Bronchitis.

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.).

Exploring Triple-Isotopic Signatures of Water in Human Exhaled Breath, Gastric Fluid, and Drinking Water Using Integrated Cavity Output Spectroscopy.

Water, the major body fluid in humans, has four main naturally occurring isotopologues, H216O, H217O, H218O, and H2H16O (i.e., HD16O) 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), δ18O = -5.41 ± 1.47‰ (SD), and δ17O = -2.92 ± 0.79‰ (SD)), GI fluid (GF; δD = -35.91 ± 7.30‰ (SD), δ18O = -3.98 ± 1.29‰ (SD), and δ17O = -2.37 ± 0.57‰ (SD)), and human exhaled breath (EB; δD = -119.63 ± 7.27‰ (SD), δ18O = -13.69 ± 1.23‰ (SD), and δ17O = -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., HD16O 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.

Investigating E-Cigarette Particle Emissions and Human Airway Depositions under Various E-Cigarette-Use Conditions.

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.

[Air pollution and its impact on the respiratory system]. / Répercussion des polluants ­environnementaux sur le système ­respiratoire chez l'adulte.

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.

De nombreuses études épidémiologiques ont montré une augmentation de la morbidité et de la mortalité liées au système respiratoire en relation avec la pollution. L'exposition aux polluants atmosphériques provoque des effets à court terme, suite à une exposition à un pic de pollution, et des effets à long terme : déclin de la fonction pulmonaire et développement de ­pathologies chroniques. Cet article explore l'impact des différents polluants atmosphériques sur la BPCO, l'asthme ainsi que le ­cancer pulmonaire. Les conséquences de la pollution domestique sur le système respiratoire ainsi que l'impact de la pollution ­atmosphérique sur l'effort physique seront également abordés.

Human respiratory system as sink for volatile organic compounds: Evidence from field measurements.

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.

Effect of Particle-Wall Interaction and Particle Shape on Particle Deposition Behavior in Human Respiratory System.

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.

Characterization of airborne particles from cleaning sprays and their corresponding respiratory deposition fractions.

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.

Patient-specific modelling of regional tobramycin concentration levels in airways of patients with cystic fibrosis: can we dose once daily?

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).

[Effect of high-fat diet on expression of transient receptor potential vanilloid 1 in respiratory tract and dorsal root ganglion of mice].

OBJECTIVE: To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons. METHODS: A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG. RESULTS: After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group (6.4±2.6 g vs 2.3±0.5 g; P<0.001). The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared with the ND group, the HFD group had significant increases in the TRPV1 current intensity and number of action potentials in the DRG (P<0.05). CONCLUSIONS: High-fat diet induces a significant increase in body weight and leads to high expression of TRPV1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.

Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition in olfactory mucosa on particle size implies that the occupation deposition of welding fume manganese can be expected to vary with welding method.

Deposition of graphene nanomaterial aerosols in human upper airways.

Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

[Airway oxidative stress and inflammation markers in chronic obstructive pulmonary diseases(COPD) patients are linked with exposure to traffic-related air pollution: a panel study].

OBJECTIVE: To investigate the effects of short-term exposure to traffic-related air pollution on airway oxidative stress and inflammation in chronic obstructive pulmonary diseases (COPD) patients. METHODS: A panel of forty-five diagnosed COPD patients were recruited and followed with repeated measurements of biomarkers reflecting airway oxidative stress and inflammation in exhaled breath condensate (EBC), including nitrate and nitrite, 8-isoprostane, interleukin-8 and acidity of EBC (pH), between 5(th) September in 2014 and 26(th) May in 2015. The associations between air pollution and biomarkers were analyzed with mixed-effects models, controlling for confounding covariates. RESULTS: The concentration of PM2.5, black carbon, NO2 and number concentration of particles with diameter less than 100 nm (PNC100), and particles in size ranges between 100 nm to 200 nm (PNC100-200) during the first follow-up were (156.5±117.7), (10.7±0.7), (165.9±66.0)µg/m(3) and 397 521±96 712, 79 421±44 090 per cubic meter, respectively; the concentration were (67.9±29.6), (3.4±1.3), (126.1±10.9) µg/m(3) and (295 682±39 430), (24 693±12 369) per cubic meter, respectively during the second follow-up. The differences were of significance, with t value being 3.10, 4.42, 2.61, 4.02, 5.12, respectively and P value being 0.005,<0.001, 0.016, <0.001 and <0.001, respectively. In our COPD-patient panel, per interquartile range (IQR) increase in PNC100-200, we observed an increase of 65% (95% CI: 8%-152%) in nitrate and nitrite in EBC reflecting airway oxidative stress. For an IQR increase in PM2.5, black carbon and PNC100-200, respective increases of 0.17 ng/ml (95% CI: 0.02-0.33), 0.12 ng/ml (95% CI: 0.01-0.24) and 0.13 ng/ml (95% CI:0.02-0.24) in interleukin-8 in EBC reflecting airway inflammation were also observed. An IQR increase in ozone was also associated with a 0.24 (95%CI: 0.05-0.42) decrease in pH of EBC reflecting increased airway inflammation. No significant association observed between air pollution and 8-isoprostane in EBC in COPD patients. CONCLUSION: Our results suggested that short-term exposure to traffic-related air pollution was responsible for exacerbation of airway oxidative stress and inflammation in COPD patients.

Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.

The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2-3- and α2-6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcß1-4)Galß1-4GlcNAc) and sialylated N,N'-diacetyllactosamine (NeuAcα2-6GalNAcß1-4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection.

Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.

The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia) acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.