Respiratory Particles Research Articles

Computational fluid dynamics simulation of aerosol transport and deposition

In this article computational fluid dynamics (CFD) simulation of aerosol transport and deposition, i.e. the transport and deposition of particles in an aerosol, is reviewed. The review gives a brief account of the basics of aerosol mechanics, followed by a description of the general CFD approach for flow field simulation, turbulence modeling, wall treatments and simulation of particle motion and deposition. Then examples from the literature are presented, including CFD simulation of particle deposition in human respiratory tract and particle deposition in aerosol devices. CFD simulation of particle transport and deposition may provide information that is difficult to obtain through physical experiments, and it may help reduce the number of experiments needed for device design. Due to the difficulty of describing turbulent flow and particle-eddy interaction, turbulent dispersion of particles remains one of the greatest challenges for CFD simulation. However, it is possible to take a balanced approach toward quantitative description of aerosol dispersion using CFD simulation in conjunction with empirical relations.

Protein Analysis of Purified Respiratory Syncytial Virus Particles Reveals an Important Role for Heat Shock Protein 90 in Virus Particle Assembly

In this study, we used imaging and proteomics to identify the presence of virus-associated cellular proteins that may play a role in respiratory syncytial virus (RSV) maturation. Fluorescence microscopy of virus-infected cells revealed the presence of virus-induced cytoplasmic inclusion bodies and mature virus particles, the latter appearing as virus filaments. In situ electron tomography suggested that the virus filaments were complex structures that were able to package multiple copies of the virus genome. The virus particles were purified, and the protein content was analyzed by one-dimensional nano-LC MS/MS. In addition to all the major virus structural proteins, 25 cellular proteins were also detected, including proteins associated with the cortical actin network, energy pathways, and heat shock proteins (HSP70, HSC70, and HSP90). Representative actin-associated proteins, HSC70, and HSP90 were selected for further biological validation. The presence of beta-actin, filamin-1, cofilin-1, HSC70, and HSP90 in the virus preparation was confirmed by immunoblotting using relevant antibodies. Immunofluorescence microscopy of infected cells stained with antibodies against relevant virus and cellular proteins confirmed the presence of these cellular proteins in the virus filaments and inclusion bodies. The relevance of HSP90 to virus infection was examined using the specific inhibitors 17-N-Allylamino-17-demethoxygeldanamycin. Although virus protein expression was largely unaffected by these drugs, we noted that the formation of virus particles was inhibited, and virus transmission was impaired, suggesting an important role for HSP90 in virus maturation. This study highlights the utility of proteomics in facilitating both our understanding of the role that cellular proteins play during RSV maturation and, by extrapolation, the identification of new potential targets for antiviral therapy.

Particle Size Distribution in Ambient Air of Delhi and Its Statistical Analysis

Particle size distribution in ambient air has been studied in an urban city, Delhi. Different activity sites namely; kerbside, industrial and residential were selected for the study. The statistical analysis was carried out to study the frequency distribution and sources of different particle size fractions. The dominance of coarse particles attributed to local activities was observed at all the sites. It was observed that at kerbside sites, up to 52% of the particles were lower respiratory tract and up to 47% of the particles were upper respiratory tract particles. At residential and industrial sites, up to 40% and 31% were lower and upper respiratory tract particles, respectively. Factor analysis results indicated auto-exhaust as the dominant source of particulate matter at two of the kerbside sites. Resuspended dust was dominant at remaining two kerbside and residential sites. It was inferred using geometric standard deviation of particle size fractions that these were from different sources at residential and industrial site and from similar sources at three of the kerbside sites.

Self-assembly of Severe Acute Respiratory Syndrome Coronavirus Membrane Protein

Coronavirus membrane (M) protein can form virus-like particles (VLPs) when coexpressed with nucleocapsid (N) or envelope (E) proteins, suggesting a pivotal role for M in virion assembly. Here we demonstrate the self-assembly and release of severe acute respiratory syndrome coronavirus (SARS-CoV) M protein in medium in the form of membrane-enveloped vesicles with densities lower than those of VLPs formed by M plus N. Although efficient N-N interactions require the presence of RNA, we found that M-M interactions were RNA-independent. SARS-CoV M was observed in both the Golgi area and plasma membranes of a variety of cells. Blocking M glycosylation does not appear to significantly affect M plasma membrane labeling intensity, M-containing vesicle release, or VLP formation. Results from a genetic analysis indicate involvement of the third transmembrane domain of M in plasma membrane-targeting signal. Fusion proteins containing M amino-terminal 50 residues encompassing the first transmembrane domain were found to be sufficient for membrane binding, multimerization, and Golgi retention. Surprisingly, we found that fusion proteins lacking all three transmembrane domains were still capable of membrane binding, Golgi retention, and interacting with M. The data suggest that multiple SARS-CoV M regions are involved in M self-assembly and subcellular localization.

Removal of exhaled particles by ventilation and deposition in a multibed airborne infection isolation room

Removal of airborne particles in airborne infection isolation rooms is important for infection control of airborne diseases. Previous studies showed that the downward ventilation recommended by Centers for Disease Control and Prevention (CDC) could not produce the expected 'laminar' flow for pushing down respiratory gaseous contaminants and removing them via floor-level exhausts. Instead, upper-level exhausts were more efficient in removing gaseous contaminants because of upward body plumes. The conventional wisdom in the current CDC-recommended design is that floor-level exhausts may efficiently remove large droplets/particles, but such a hypothesis has not been proven. We investigated the fate of respiratory particles in a full-scale six-bed isolation room with exhausts at different locations by both experimental and computational studies. Breathing thermal manikins were used to simulate patients, and both gaseous and large particles were used to simulate the expelled fine droplet nuclei and large droplets. Gaseous and fine particles were found to be removed more efficiently by ceiling-level exhausts than by floor-level exhausts. Large particles were mainly removed by deposition rather than by ventilation. Our results show that the existing isolation room ventilation design is not effective in removing both fine and large respiratory particles. An improved ventilation design is hence recommended. Our findings of the relatively poor performance of fine-particle removal by the existing CDC design of isolation room ventilation suggests a need for improvement, and the findings of the removal of large particles by deposition, not by ventilation, suggest that floor-level exhausts are unnecessary, and that regular surface cleaning and disinfection is necessary, thus providing evidence for maintaining isolation room surface hygiene.

Diesel Exhaust Particle (DEP)‐Induced Acute Loss of Respiratory Neutral Endopeptidase

Neutral endopeptidase (NEP) is a key cell surface peptidase in the maintenance of airway homeostasis involving the development of pulmonary disorders. However, little information is available about the effect of respiratory particles on airway NEP. Cross‐shift spirometry and sputum NEP were measured on twelve normal subjects following acute diesel exhaust exposure. A significant increase in soluble NEP in sputum was observed with 31% average net increases when compared with pre‐exposure. Pearson's correlation analyses indicated that changes in sputum NEP activity were significantly associated with diesel exhaust particle (DEP) exposure. DEP exposure also induced a significant decline in forced expiratory volume in one second (FEV1, 4.03 ± 0.29 vs. 3.78 ± 0.29; p = 0.005 pre‐ vs. post exposure) and forced vital capacity (FVC, 5.16 ± 0.36 vs. 4.86 ± 0.39, p = 0.017), which were significantly associated with sputum NEP activity, not with DEP exposure. The changes in NEP activity may be an accurate endpoint for DEP exposure, be mechanistically linked to lung function, and indicate a greater susceptibility to the risk of pulmonary diseases.

Study on airflow and inhaled particle deposition within realistic human upper respiratory tract

Based on the CT (Computerized Tomography) scanned images of a 19-years-old healthy boy, a realistic geometric model of URT from nasal cavity to the upper six-generation bronchial is rebuilt. To investigate airflow and particle deposition in the obtained realistic human upper respiratory tract, RNG k-ϵ turbulence model was used to describe the primary flow and particle deposition under three breathing intensity such as 15 L/min, 30 L/min and 60 L/min. The particle is tracked and analyzed in the Lagrangian frame. The velocity fields of airflow under different airflow rates were computed and discussed. The trapping of particles with diameter 1μm on the wall surfaces was monitored, and the locations of trapping in different region were visualized.In order to study the characteristics of particles movement and the effect of particles diameter on the deposition pattern, eleven kinds of sphere particles with different diameters are selected as research object. The diameters of selected particles as follows: 0.1μm, 0.5μm, 1μm, 2.5μm, 3μm, 3.5μm, 4μm, 4.5μm, 5μm, 6.5μm and 8μm. The variation of inhalable particles deposition in realistic human upper respiratory tract with respiratory intensity and particle size was researched and compared.

Particle Size Distribution of Airborne Microorganisms and Pathogens during an Intense African Dust Event in the Eastern Mediterranean

BackgroundThe distribution of microorganisms, and especially pathogens, over airborne particles of different sizes has been ignored to a large extent, but it could have significant implications regarding the dispersion of these microorganisms across the planet, thus affecting human health.ObjectivesWe examined the microbial quality of the aerosols over the eastern Mediterranean region during an African storm to determine the size distribution of microorganisms in the air.MethodsWe used a five-stage cascade impactor for bioaerosol collection in a coastal city on the eastern Mediterranean Sea during a north African dust storm. Bacterial communities associated with aerosol particles of six different size ranges were characterized following molecular culture–independent methods, regardless of the cell culturability (analysis of 16S rRNA genes).ResultsAll 16S rDNA clone libraries were diverse, including sequences commonly found in soil and marine ecosystems. Spore-forming bacteria such as Firmicutes dominated large particle sizes (> 3.3 μm), whereas clones affiliated with Actinobacteria (found commonly in soil) and Bacteroidetes (widely distributed in the environment) gradually increased their abundance in aerosol particles of reduced size (< 3.3 μm). A large portion of the clones detected at respiratory particle sizes (< 3.3 μm) were phylogenetic neighbors to human pathogens that have been linked to several diseases.ConclusionsThe presence of aerosolized bacteria in small size particles may have significant implications to human health via intercontinental transportation of pathogens.

미세먼지가 울산지역 초등학생의 폐기능에 미치는 영향

To evaluate the effect of air pollution on respiratory health in children, We conducted a longitudinal study in which children were asked to record their daily levels of Peak Expiratory Flow Rate(PEFR) using potable peak flow meter(mini-Wright) for 4 weeks. The relationship between daily PEFR and ambient air particle levels was analyzed using a mixed linear regression models including gender, age in year, weight, the presence of respiratory symptoms, and relative humidity as an extraneous variable. The daily mean concentrations of <TEX>$PM_{10}$</TEX> and <TEX>$PM_{2.5}$</TEX> over the study period were <TEX>$64.9{\mu}g/m^3$</TEX> and <TEX>$46.1{\mu}g/m^3$</TEX>, respectively. The range of daily measured PEFR in this study was <TEX>$182{\sim}481\;l/min$</TEX>. Daily mean PEFR was regressed with the 24-hour average <TEX>$PM_{10}(or\;PM_{2.5})$</TEX> levels, weather information such as air temperature and relative humidity, and individual characteristics including sex, weight, and respiratory symptoms. The analysis showed that the increase of air particle concentrations was negatively associated with the variability in PEFR. We estimated that the IQR increment of <TEX>$PM_{10}$</TEX> or <TEX>$PM_{2.5}$</TEX> were associated with 1.5 l/min (95% Confidence intervals -3.1, 0.1) and 0.8 l/min(95% CI -1.8, 0.1) decline in PEFR. Even though this study showed negative findings on the relationship between respiratory function and air particles, it was worth noting that the findings must be interpreted cautiously because exposure measurement based on monitoring of ambient air likely resulted in misclassification of true exposure levels and this was the first Korean study that <TEX>$PM_{2.5}$</TEX> measurement was applied as an index of air quality.

154. Severe Acute Respiratory Syndrome Coronavirus-Like Particles (SARS-CoVLPs) Stimulate Human Monocyte-Derived Dendritic Cell Activity and Induce Antibody Response in Mouse Model

154. Severe Acute Respiratory Syndrome Coronavirus-Like Particles (SARS-CoVLPs) Stimulate Human Monocyte-Derived Dendritic Cell Activity and Induce Antibody Response in Mouse Model

Changing health care worker behavior in relation to respiratory disease transmission with a novel training approach that uses biosimulation

BackgroundThis pilot study was conducted to determine whether supplementing standard classroom training methods regarding respiratory disease transmission with a visual demonstration could improve the use of personal protective equipment among emergency department nurses.MethodsParticipants included 20 emergency department registered nurses randomized into 2 groups: control and intervention. The intervention group received supplemental training using the visual demonstration of respiratory particle dispersion. Both groups were then observed throughout their work shifts as they provided care during January-March 2005.ResultsParticipants who received supplemental visual training correctly utilized personal protective equipment statistically more often than did participants who received only the standard classroom training.ConclusionSupplementing the standard training methods with a visual demonstration can improve the use of personal protective equipment during care of patients exhibiting respiratory symptoms.

Particle deposition in obstructed airways

One approach to tackle the particle deposition in human lungs in close proximity is to develop an understanding of the particle motion in bifurcation airways. Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in humans. COPD always results in inflammation that leads to narrowing and obstructing of the airways. The obstructive airways can alter the respiratory flow and particle deposition significantly. In order to study the effect of obstruction on particle deposition, four three-dimensional four-generation lung models based on the 23-generation model of Weibel [1963. Morphometry of the Human Lung. New York Academic Press, Springer, Berlin.] have been generated. The fully three-dimensional incompressible laminar Navier–Stokes equations are solved using computational fluid dynamics (CFD) solver on structured hexahedral meshes. Subsequently, a symmetric four-generation airway model serves as the reference and the other three models are considered to be obstructed at each generation, respectively. The calculation results show that the obstructive airway has significant influence on the particle deposition down-stream of the obstruction. The skewed velocity profile in the bifurcation airway is modified by the throat; consequently, more particles impact on the divider which results in higher deposition efficiency.

Effervescent dry powder for respiratory drug delivery

The objective of this work was to develop a new type of respiratory drug delivery carrier particle that incorporates an active release mechanism. Spray drying was used to manufacture inhalable powders containing polybutylcyanoacrylate nanoparticles and ciprofloxacin as model substances for pulmonary delivery. The carrier particles incorporated effervescent technology, thereby adding an active release mechanism to their pulmonary route of administration. Effervescent activity of the carrier particles was observed when the carrier particles were exposed to humidity. Gas bubbles caused by the effervescent reaction were visualized by confocal laser scanning microscopy. The images showed that nanoparticles were distributed throughout the gas bubble. For the effervescent formulation the average mass median aerodynamic diameter (MMAD) was 2.17 μm ± 0.42, fine particle fraction (FPF <=5.6 μm ) was 46.47% ± 15 and the GSD was 2.00 ± 0.06. The results also showed that the effervescent carrier particles released 56 ± 8% ciprofloxacin into solution compared with 32 ± 3% when lactose carrier particles were used. The mean nanoparticle size did not significantly change upon release when the nanoparticles were incorporated into an effervescent formulation. However, the mean size significantly increased upon release when only lactose was used as carrier particle matrix. In conclusion, effervescent carrier particles can be synthesized with an adequate particle size for deep lung deposition. This opens the door for future research to explore this technology for delivery of a large range of substances to the lungs with possible improved release compared to conventional carrier particles.

Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers

Background: A 1998 survey at a beryllium oxide ceramics manufacturing facility found that 10% of workers hired in the previous 6 years had beryllium sensitisation as determined by the beryllium...

Living near Main Streets and Respiratory Symptoms in Adults

The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), conducted in 1991 (SAPALDIA 1) in eight areas among 9,651 randomly selected adults aged 18-60 years, reported associations among the prevalence of respiratory symptoms, nitrogen dioxide, and particles with an aerodynamic diameter of less than 10 microg/m3. Later, 8,047 subjects reenrolled in 2002 (SAPALDIA 2). The effects of individually assigned traffic exposures on reported respiratory symptoms were estimated, while controlling for socioeconomic and exposure- and health-related factors. The risk of attacks of breathlessness increased for all subjects by 13% (95% confidence interval: 3, 24) per 500-m increment in the length of main street segments within 200 m of the home and decreased in never smokers by 12% (95% confidence interval: 0, 22) per 100-m increment in distance from home to a main street. Living within 20 m of a main street increased the risks of regular phlegm by 15% (95% confidence interval: 0, 31) and wheezing with breathing problems by 34% (95% confidence interval: 0, 79) in never smokers. In 2002, the effects related to road distance were different from those in 1991, which could be due to changes in the traffic pollution mixture. These findings among a general population provide strong confirmation that living near busy streets leads to adverse respiratory health effects.

Blue Ribbon Abstract Award

BACKGROUND/OBJECTIVES: Respiratory disease transmission continues to be an area of safety concern for healthcare personnel (HCP). We describe an experiment that uses a novel training method to demonstrate dispersion of particles during respiration and cough within the context of respiratory disease transmission. The study was conducted to determine whether supplementing standard classroom training methods regarding disease transmission with a visual demonstration can improve the use of PPE among Emergency Department (ED) nurses. METHODS: Participants in a pilot study included 20 ED registered nurses. General demographic information was obtained. All subjects first participated in classroom training dealing with infection control and disease transmission then completed a pre- and post-test to determine knowledge level. Subjects were then randomized into two groups, control and intervention. The intervention group received supplemental training consisting of a visual demonstration of respiratory particle dispersion using a human biosimulator. Both groups were then observed throughout their work shifts as they provided care during January-March 2005. RESULTS: Both the intervention group and the control group completed standard classroom training. The pre classroom training knowledge assessment indicated no difference between the intervention and control groups (t(19) = 1.11, p=.28). In the final dataset, there were 84 observations evaluated with 42 in each group. A Fisher's Exact test was performed to determine if the visual demonstration increased appropriate PPE use relative to the standard training alone. Results indicate that the standard training plus biosimulation significantly increased the use of PPE by nurses when providing care for patients with respiratory symptoms (p = .04). CONCLUSIONS: Analysis comparing the use of PPE between the subjects trained with or without a visual demonstration indicated that those who received the visual demonstration used PPE more often. The additional training resulted in a 21% increase in the use of PPE (74% versus 53%). This indicates that supplementing the standard training methods with a visual demonstration can improve the use of PPE by nurses when providing care for patients exhibiting respiratory symptoms. Supported by the <i>Research Foundation for Prevention of Complications Associated with Health Care</i> and cooperative agreements with the <i>Health Resources and Services Administration</i> and the <i>Centers for Disease Control and Prevention.</i>

"Going Smoke Free" - BMA booklet review.

"Going Smoke Free" - BMA booklet review.

694. Involvement of Glycosaminoglycans in VSV-G Pseudotyped Lentiviral Vector Mediated Gene Transfer into Airway Epithelial Cells

HIV-1-derived lentiviral (LV) vectors are considered promising vehicles for Cystic Fibrosis (CF) gene therapy since they integrate in the host genome, transduce non-dividing cells and ensure long-term expression of the transgene. Although some knowledge on the infection of respiratory epithelial cells has been accumulated, the receptors involved in the transduction of these cells by VSV-G-pseudotyped LV vectors are not well known. Previous studies have shown that heparin inhibited infection of HT1080 cells by Moloney Murine Leukemia retrovirus pseudotyped with VSV-G (Guibinga, 2002), indicating that interaction with glycosaminoglycans (GAGs) of cellular membrane plays a role in infectivity of viral particles with VSV-G envelope. Our study investigated the involvement of heparan sulfate (HS) and chondroitin sulfate B in gene transfer mediated by a VSV-G pseudotyped LV vector in a respiratory epithelial cell line of tracheal origin (CFT1-C2). The HIV-1 derived LV vector PPT-GFP carries the Green Fluorescence Protein (GFP) reporter gene under the control of the CMV promoter (Follenzi, 2000). To evaluate the interaction between GAGs expressed on the apical surface of respiratory epithelial cells and lentiviral particles, the LV vector (3.2|[times]|10E8 TU, corresponding to MOI 2000) was pre-incubated with heparin or chondroitin sulfate B at different concentrations (10|[ndash]|250 micrograms/ml) for 60 minutes in binding buffer and then added to polarized CFT1-C2 cells (polarization was evaluated by the measure of transepithelial resistance and apical expression of ZO-1). The virus-containing solution was incubated with cells for 24 hours and GFP expression was analyzed by flow cytometry 72 hours after. Heparin and chondroitin sulfate B determined a dose-dependent inhibition of transduction efficiency up to 86% and 83% of untreated vector, respectively. HS expression in CFT1-C2 cells was analyzed by flow cytometry and confocal microscopy. HS was expressed by 85|[ndash]|88% of cells, the expression being much stronger on the basolateral side of polarized cells. Cells were incubated with 12 mM EGTA before LV administration to disrupt the epithelial tight junctions and allow the lentiviral particles to access the basolateral side of the epithelium. In the absence of EGTA, 60% of cells resulted GFP positive, whereas the pre-treatment with EGTA increased the percentage of GFP-expressing cells up to 80.5%. Our data strongly indicate that the little amount of GAGs restricted to the apical surface might be sufficient to mediate transduction of respiratory epithelial cells by a VSV-G pseudotyped LV vector. However, we can not exclude that other receptor(s) could be involved.

Bioaerosol Mass Spectrometry for Rapid Detection of Individual Airborne Mycobacterium tuberculosis H37Ra Particles

Single-particle laser desorption/ionization time-of-flight mass spectrometry, in the form of bioaerosol mass spectrometry (BAMS), was evaluated as a rapid detector for individual airborne, micron-sized, Mycobacterium tuberculosis H37Ra particles, comprised of a single cell or a small number of clumped cells. The BAMS mass spectral signatures for aerosolized M. tuberculosis H37Ra particles were found to be distinct from M. smegmatis, Bacillus atrophaeus, and B. cereus particles, using a distinct biomarker. This is the first time a potentially unique biomarker was measured in M. tuberculosis H37Ra on a single-cell level. In addition, M. tuberculosis H37Ra and M. smegmatis were aerosolized into a bioaerosol chamber and were sampled and analyzed using BAMS, an aerodynamic particle sizer, a viable Anderson six-stage sampler, and filter cassette samplers that permitted direct counts of cells. In a background-free environment, BAMS was able to sample and detect M. tuberculosis H37Ra at airborne concentrations of >1 M. tuberculosis H37Ra-containing particles/liter of air in 20 min as determined by direct counts of filter cassette-sampled particles, and concentrations of >40 M. tuberculosis H37Ra CFU/liter of air in 1 min as determined by using viable Andersen six-stage samplers. This is a first step toward the development of a rapid, stand-alone airborne M. tuberculosis particle detector for the direct detection of M. tuberculosis bioaerosols generated by an infectious patient. Additional instrumental development is currently under way to make BAMS useful in realistic environmental and respiratory particle backgrounds expected in tuberculosis diagnostic scenarios.

Assembly of human severe acute respiratory syndrome coronavirus-like particles

Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. In this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. We found that the membrane and envelope proteins are sufficient for the efficient formation of virus-like particles and could be visualized by electron microscopy. Sucrose gradient purification followed by Western blot analysis and immunogold labeling showed that the spike protein could be incorporated into the virus like particle also. The construction of engineered virus-like particles bearing resemblance to the authentic one is an important step towards the development of an effective vaccine against infection of SARS CoV.