Aerodynamic Particle Sizer Research Articles

Associations of personal exposure to domestic heating and cooking fuel emissions and epidemiological effects on rural residents in the Fenwei Plain, China

Solid fuel combustion for domestic heating in northern China in the wintertime is of great environmental and health concern. This study assesses personal exposure to particulate matter with different aerodynamic diameters and multiple gaseous pollutants from 123 rural residents in Yuncheng, the Fenwei Plain. The subjects are divided into groups based on the unique energy source applied, including biomass, coal, and electricity/no heating activities. The health effects of the exposures are expressed with four urinary biomarkers. The personal exposure levels to three different aerodynamic particle sizes (i.e., PM10, PM2.5, and PM1) of the electricity/no heating group are 5.1 % –12 % lower than those of the coal group. In addition, the exposure levels are 25 %–40 % lower for carbon monoxide (CO) and 10.8 %–20.3 % lower for ozone (O3) in the electricity/no heating group than the other two fuel groups. C-reactive protein (CRP) in the urine of the participants in biomass and coal groups is significantly higher than that in the electricity/no heating group, consistent with the observations on other biomarkers. Increases in 8-hydroxy-2 deoxyguanosine (8-OHdG), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) are observed for the exposures to higher concentrations of air pollutants. For instance, PMs and nitrogen dioxide (NO2) show significant impacts on positive correlations with 8-OHdG and IL-8, while O3 positively correlates with CRP. PM1 exhibits higher effects on the biomarkers than the gaseous pollutants, especially on VEGF and IL-8. The study indicates that excessive use of traditional domestic solid fuels could pose severe health effects on rural residents. The promotion of using clean energy is urgently needed in the rural areas of northern China.

Optimization and Scale Up of Spray Dried CPZEN-45 Aerosol Powders for Inhaled Tuberculosis Treatment.

PurposeTuberculosis (TB) remains one of the most serious diseases caused by a single organism. Multiple (MDR) and extensively (XDR) drug resistant disease poses a threat to global health and requires new drugs and/or innovative approaches to treatment. A number of drugs have been proposed as inhaled therapy for TB, frequently prepared by spray drying. CPZEN-45 is a novel anti-tubercular drug that has poor oral bioavailability but has shown promise when administered via inhalation.MethodsExcipient-free CPZEN-45 HCl has been spray dried into a powder with physicochemical characteristics, aerodynamic particle size distribution, and delivered dose suitable for consideration as an inhaled product.ResultsThe mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the powder delivered using a RS01 inhaler were 2.62 ± 0.04 μm and 1.76 ± 0.09, respectively. Additionally, the powder was physically and chemically stable after storage at ambient conditions for >1.5 years with particle size similar to freshly manufactured product. Overages in spray dried powder were recycled the powder and resprayed into drug product likewise resulting in negligible change in quality thus allowing for further preclinical characterization as necessary. CPZEN-45 was scaled up using pilot-scale manufacturing equipment where the density of the powder was increased to facilitate larger delivered doses without affecting the aerodynamic performance properties.ConclusionThe spray dried powders were suitable for pharmacokinetics, efficacy and preclinical toxicology studies. The final method of manufacture may be used directly for CGMP particle manufacture to support IND and Phase I clinical trials and beyond.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11095-022-03393-w.

Comparison of the Chemical Characteristics and Toxicity of PM2.5 Collected Using Different Sizes of Cyclones

Cyclone sampling devices have been helpful in assessing the toxic effects of fine particulate matter (PM2.5). The particle collection efficiency of sampling devices is critical. This study investigated the effect of cyclone size on particle size, chemical composition, and particle toxicity. Three cyclones with different inner diameters (12–68 mm) were tested for penetration using an aerodynamic particle sizer, fluorescent polystyrene latex, and a differential mobility analyzer. The elemental and water-soluble ion compositions of the particles collected by different cyclones were compared. An evaluation of the particles’ toxicity was conducted by comparing the results of dithiothreitol (DTT), limulus amebocyte lysate (LAL), and cell exposure assays. The experimental evaluation showed a 50% cut-size of the cyclones between 0.17–0.28, 0.34–0.36, and 0.70 μm for the small, medium, and large cyclones, respectively. To collect PM2.5 and evaluate separation performance in the real environment, the small and large cyclones were selected according to the particle penetration and flow rate. A comparison of chemical composition and enrichment factor values found that the particles in the small cyclone samples contained smaller and more anthropogenic sources than those in the large cyclone samples. The oxidative potential (OP) measured by the DTT assay of the samples collected using the small and large cyclones differed across sampling periods and associated with the transition metals. The viability of human epithelial A549 cells after exposure to the collected particles using the cyclones was different across sampling periods and associated with OP. The endotoxin concentrations measured in the LAL assay were found only in the large cyclone samples; they affected the estimated level of cytokine based on IL(interleukin)-6 release from human leukemia monocytic (THP-1) cells derived macro-phage-like cells. Regardless of the size, the cyclone techniques used in this study to collect aerosol particles would be a powerful tool for a detailed evaluation of particle toxicity.

Optimizing the design and dosing of dry powder inhaler formulations of the cationic liposome adjuvant CAF®01 for pulmonary immunization

Thermostability is one of the product characteristics preferred by WHO for vaccines against respiratory infections due to ease of administration, pain minimization, and low costs. Thermostable dry powder inhaler (DPI) vaccine formulations can induce protective antibodies and T cells at the site of infection in the lungs. However, the majority of licensed human vaccines is based on liquid dosage forms, and there is no licensed mucosal adjuvants. The cationic adjuvant formulation 01 (CAF®01) is a liposome-based adjuvant system that (i) induces robust T cells and antibodies, (ii) is safe and well-tolerated in clinical trials, and (iii) induces mucosal immune responses after pulmonary administration. However, the optimal DPI formulations of CAF®01 for pulmonary immunization are not known. Here, we show that DPI formulations of CAF®01 spray-dried with a combination of sugars and the amino acid leucine exhibit optimal aerosolization properties and distribute in the lung lobes upon pulmonary administration. We demonstrate that the type of amorphous sugar used as stabilizer and the amount (w/w) of leucine used during spray drying affect the physicochemical properties and aerosol performance of DPI formulations. By systematically varying the ratios (w/w) of trehalose, dextran and leucine used as excipients during spray drying, we manufactured DPI formulations of CAF®01 that displayed (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) solid-state and aerosolization properties suitable for lung delivery. Using a design-of-experiments-based approach, we identified the most optimal process parameters in an in vivo aerosol generator, i.e., the PreciseInhale® system, which was used to measure the flowability of the aerosols. We found that the DPI formulation of CAF®01 spray-dried with trehalose and dextran (70% w/w) and leucine (30% w/w) displayed the most optimal physicochemical, morphological, solid-state, and aerosolization properties for deep lung deposition. Upon pulmonary administration, this DPI formulation distributed in the lung lobes in a way that was almost identical to the biodistribution of the non-spray dried formulation. Hence, DPI formulations of CAF®01, prepared with trehalose and dextran sugar matrix and a leucine shell, display physicochemical and aerosol properties suitable for inhalation.

Detection of Particle Concentration and Particle Size Based on Aerodynamic Particle Size Spectrometer

In order to solve the problem of the continuous online monitoring of the fixed pollution source emission particles, on the basis of the advantages and disadvantages of the comprehensive analysis of the extinction method, the β-ray absorption method, the micro-oscillating balance method, the charge transfer method, and the light scattering method, the particle size distribution and concentration optical detection system based on aerodynamic particle size spectrometer is designed according to the Mie light scattering principle. A high-performance aerodynamic particle size spectrometer is designed using a single-wavelength method to measure the concentration of particulate matter, and the equipment and the detection system are used in the continuous monitoring of particulate matter emitted by thermal power plants and compared with the ES632 equipment. Through the system test, the results show that compared with the ES632 equipment performance, the lowest concentration measured by the design of aerodynamic particle size spectrometer equipment can reach 0.1 mg/m3 with a measurement accuracy of 0.01 mg/m3. Compared with the ES632 equipment, the measurement concentration value is 8% higher, which meets the test requirements.

Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats.

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 μm, whereas the mass median aerodynamic diameter was 5.9 μm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process.

Validation of a cell integrated next-generation impactor to assess in vitro drug transport of physiologically relevant aerosolised particles

The development of novel inhaled formulations in the pre-clinical stage has been impeded by a lack of meaningful information related to drug dissolution and transport at the lung epithelia due to the absence of physiologically relevant in vitro respiratory models. The objective of the present study was to develop an in vitro experimental model, which combined the next generation impactor (NGI) and two respiratory epithelial cell lines, for examining the aerodynamic performance of dry powder inhalers and the fate of aerosolised drugs following lung deposition. The NGI impaction plates of stage 3 (i.e., a cut-off diameter of 2.82–4.46 µm) and stage 7 (i.e., a cut-off diameter of 0.34–0.55 µm) were modified to accommodate 3 cell cultures inserts. Specifically, Calu-3 cells and H441 cells, which are representative of the bronchial and alveolar epithelia in the lung, respectively, were cultivated at the air–liquid interface on SnapwellsTM with polycarbonate membranes. The aerodynamic particle size distribution of the modified NGI was investigated using resveratrol dry powder formulation (as a model drug). The suitability of such an in vitro model was confirmed by examining the in vitro aerodynamic performance of the model drug as compared to the conventional NGI setup (i.e., without the integrated Snapwell inserts), as well as the effect of experimental conditions (e.g., 60 L/min airflows) on the cells in the integrated Snapwell inserts. After deposition of the aerodynamically fractioned resveratrol, the permeation of the drug across the cell layer to the basolateral chamber of the Snapwell inserts was evaluated over 24 h. Results obtained from the drug transport study showed that the cell-integrated NGI provided realistic drug delivery conditions to the cells that can be used to assess the fate of fractionated aerosol particles. This system enables a better understanding of the in vitro drug deposition in the lungs and allows studies on both aerodynamic characterisation and drug transport (drug biological interactions with the cells) to be performed simultaneously.

Characterization and size distribution of initial droplet concentration discharged from human breathing and speaking

A study of the aerodynamic characteristics of aerosol expiration is important for understanding the size distribution of droplet concentration in COVID-19 disease transmission. This study measured the initial concentration and size distribution of droplets released during four breathing processes: nose breathing, mouth breathing, reading alphabets and counting numbers. Influencing factors on droplet generation were studied by statistical analyses. Significant differences in droplet concentration among the four breathing activities in pairs were found ( p < 0.001), except for reading alphabets and numbers ( p = 1). The droplet concentration during nose breathing ( p < 0.05), but not mouth breathing ( p = 0.136), of male subjects, was found significantly higher than that of female subjects. The droplet concentration generated by speaking during letters reading with special phonemes, for example, /i:/, was significantly ( p < 0.05) higher than reading letters without phonemes. The discharged droplet sizes from four breathing activities were dominated by small droplets ( dp < 1.037 μm of over 50% and dp < 2.642 μm of over 80%). Basically, no particles larger than 8 μm were detected by the aerodynamic particle sizer. The inference indicates a possible aerosol transmission of disease during non-symptomatic aerosol-producing activities such as breathing or speaking and may elucidate the disease transmission pathway of COVID-19.

Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: In vitro aerodynamic and cell line measurements

Pulmonary drug administration provides a platform for the effective local treatment of various respiratory diseases. Application of nano-sized active ingredients results in higher bioavailability because of their large specific surface area. Extra-fine dry powder inhalers reach the smaller airways, further improving therapeutic efficiency. Poorly water-soluble meloxicam was the selected active ingredient. We aimed to decrease the particle size into the nano range by wet milling and producing extra-fine inhalable particles via nano spray-drying. The diameter of the drug was reduced to 138 nm. The particle size of the dry products was between 1.1 and 1.5 µm, and the dispersed diameter was between 500 and 800 nm. Owing to the excipients (poly-vinyl-alcohol, leucine), the spray-dried particles presented nearly spherical morphology. The drug became partially amorphous. Thanks to the improved surface area, the solubility and the released and the diffused amount of the meloxicam increased in artificial lung media. The in vitro aerodynamic measurements showed that the leucine-containing formulations had outstanding fine particle fraction (FPF) deposition with 1.3 µm mass median aerodynamic diameter (MMAD). The aerodynamic particle counter test also proved the extra-fine aerodynamic particle size. The in vitro cell line experiments revealed the non-cytotoxicity of the products and the suppression of the interleukin concentration. Overall, the powders are suitable for deep pulmonary delivery and the local treatment of lung inflammations.

Relationships between Aerosol and Raindrop Size Distributions during Rainfall Period (Changma) in Jeju Island, Korea

To investigate the variation in aerosol particles removed by rainfall, we determined the relationship between aerosols and raindrops observed on Jeju Island, Korea, during a heavy rainfall period (Changma) from 1–15 July 2012. Various instruments, including an aerodynamic particle sizer, rain gauge, and disdrometer, were installed at the Gosan meteorological observation site on Jeju Island. During the Changma period, precipitation between 0.7 and 25.4 mm per day was recorded, and large variations in aerosol and raindrop size distributions were observed. Aerosol removal by precipitation was indicated, and its scavenging effect was confirmed from the results. Three major parameters (Brownian diffusion, interception, and impaction) described the collision efficiency based on aerosol and raindrop size distributions. The variations in the scavenging coefficient and below-cloud scavenging rate produced similar results for the accumulated rain amount. Therefore, these field observations explained the relationship between aerosol and raindrop size distributions.

Particle Size-dependent Dissolution of Uranium Aerosols in Simulated Lung Fluid: A Case Study in a Nuclear Fuel Fabrication Plant.

Inhalation exposure to uranium aerosols can be a concern in nuclear fuel fabrication. The ICRP provides default absorption parameters for various uranium compounds but also recommends determination of material-specific absorption parameters to improve dose calculations for individuals exposed to airborne radioactivity. Aerosol particle size influences internal dosimetry calculations in two potentially significant ways: the efficiency of particle deposition in the various regions of the respiratory tract is dependent on aerodynamic particle size, and the dissolution rate of deposited materials can vary according to particle size, shape, and porosity because smaller particles tend to have higher surface-to-volume ratios than larger particles. However, the ICRP model assumes that deposited particles of a given material dissolve at the same rate regardless of size and that uptake to blood of dissolved material normally occurs instantaneously in all parts of the lung (except the anterior portion of the nasal region, where zero absorption is assumed). In the present work, the effect of particle size on dissolution in simulated lung fluid was studied for uranium aerosols collected at the plant, and its influence on internal dosimetry calculations was evaluated. Size fractionated uranium aerosols were sampled at a nuclear fuel fabrication plant using portable cascade impactors. Absorption parameters, describing dissolution of material according to the ICRP Human Respiratory Tract Model, were determined in vitro for different size fractions using simulated lung fluid. Samples were collected at 16 time-points over a 100-d period. Uranium content of samples was determined using inductively coupled plasma mass spectrometry and alpha spectrometry. In addition, supplementary experiments to study the effect of pH drift and uranium adsorption on filter holders were conducted as they could potentially influence the derived absorption parameters. The undissolved fraction over time was observed to vary with impaction stage cut-point at the four main workshops at the plant. A larger fraction of the particle activity tended to dissolve for small cut-points, but exceptions were noted. Absorption parameters (rapid fraction, rapid rate, and slow rate), derived from the undissolved fraction over time, were generally in fair agreement with the ICRP default recommendations for uranium compounds. Differences in absorption parameters were noted across the four main workshops at the plant (i.e., where the aerosol characteristics are expected to vary). The pelletizing workshop was associated with the most insoluble material and the conversion workshop with the most soluble material. The correlation between derived lung absorption parameters and aerodynamic particle size (impactor stage cut-point) was weak. For example, the mean absorption parameters derived from impaction stages with low (taken to be <5 μm) and large (≥5 μm) cut-points did not differ significantly. Drift of pH and adsorption on filter holders appeared to be of secondary importance, but it was found that particle leakage can occur. Undissolved fractions and to some degree derived lung absorption parameters were observed to vary depending on the aerodynamic size fraction studied, suggesting that size fractionation (e.g., using cascade impactors) is appropriate prior to conducting in vitro dissolution rate experiments. The 0.01-0.02 μm and 1-2 μm size ranges are of particular interest as they correspond to alveolar deposition maxima in the Human Respiratory Tract Model (HRTM). In the present work, however, the dependency on aerodynamic size appeared to be of minor importance, but it cannot be ruled out that particle bounce obscured the results for late impaction stages. In addition, it was noted that the time over which simulated lung fluid samples are collected (100 d in our case) influences the curve-fitting procedure used to determine the lung absorption parameters, in particular the slow rate that increased if fewer samples were considered.

A comparison of respiratory particle emission rates at rest and while speaking or exercising

BackgroundThe coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies.MethodsAerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54–20 μm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test.ResultsWe present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57–0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s−1; minute ventilation (VE) 15.1 L min−1) and vigorous exercise (0.207 ng s−1, p = 0.726; VE 62.6 L min−1) is similar, but lower than during very vigorous exercise (0.682 ng s−1, p < 0.001; VE 113.6 L min−1).ConclusionsVocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced.

Risk assessment of consumer spray products using in vitro lung surfactant function inhibition, exposure modelling and chemical analysis

Consumer spray products release aerosols that can potentially be inhaled and reach the deep parts of the lungs. A thin layer of liquid, containing a mixture of proteins and lipids known as lung surfactant, coats the alveoli. Inhibition of lung surfactant function can lead to acute loss of lung function. We focused on two groups of spray products; 8 cleaning and 13 impregnation products, and in the context of risk assessment, used an in vitro method for assessing inhibition of lung surfactant function. Original spray-cans were used to generate aerosols to measure aerodynamic particle size distribution. We recreated a real-life exposure scenario to estimate the alveolar deposited dose. Most impregnation products inhibited lung surfactant function at the lowest aerosolization rate, whereas only two cleaning products inhibited function at the highest rates. We used inhibitory dose and estimated alveolar deposition to calculate the margin of safety (MoS). The MoS for the inhibitory products was ≤1 for the impregnation products, while much larger for the cleaning products (>880). This risk assessment focused on the risk of lung surfactant function disruption and provides knowledge on an endpoint of lung toxicity that is not investigated by the currently available OECD test guidelines.

Radiolabeling Method for Lyophilizate for Dry Powder Inhalation Formulations

Human lung deposition data is non-mandatory for drug approval but very useful for the development of orally inhaled drug products. Lung deposition of inhaled drugs can be quantified by radionuclide imaging, for which one of the first considerations is the method used to radiolabel formulations. In this study, we report the development of a radiolabeling method for lyophilizate for dry powder inhalation (LDPI) formulations. TechneCoatTM is one method that can radiolabel drug particles without using solvents. In this method, particles are radiolabeled with a dispersion of 99mTc-labeled nanoparticles called TechnegasTM. Because a LDPI formulation is not comprised of particles but is a lyophilized cake aerosolized by air impact, the TechneCoat method cannot be used for the radiolabeling of LDPI formulations. We therefore modified the TechneCoat apparatus so that LDPI formulations were not aerosolized by the Technegas flow. Radiolabeling using a modified TechneCoat apparatus was validated with model LDPI formulations of interferon alpha (IFN). IFN of 99mTc-unlabeled, IFN of 99mTc-labeled, and 99mTc of 99mTc-labeled LDPI formulations showed similar behavior, and differences from IFN of 99mTc-unlabeled LDPI formulations were within ±15% in aerodynamic particle size distribution measurement. Our radiolabeling method for LDPI formulations may be useful for the quantification of drug deposition in human lungs.

An experimental method for efficiently evaluating the size-resolved sampling efficiency of liquid-absorption aerosol samplers

Aerosol samplers are critical tools for studying indoor and outdoor aerosols. Development and evaluation of samplers is often labor-intensive and time-consuming due to the need to use monodisperse aerosols spanning a range of sizes. This study develops a rapid experimental methodology using polydisperse solid aerosols to evaluate size-resolved aerosol-to-aerosol (AtoA) and aerosol-to-hydrosol (AtoH) sampling efficiencies. Arizona Test Dust (diameter 0.5–20 µm) was generated and dispersed into an aerosol test chamber and two candidate samplers were tested. For the AtoA test, aerosols upstream and downstream of a sampler were measured using an online aerodynamic particle sizer. For the AtoH test, aerosols collected in sampling medium were mixed with a reference sample and then measured by the laser diffraction method. The experimental methodology were validated as an impressive time-saving procedure, with reasonable spatial uniformity and time stability of aerosols in the test chamber and an acceptable accuracy of absolute mass quantification of collected particles. Evaluation results showed that the AGI-30 and the BioSampler sampler had similar size-resolved sampling efficiencies and that efficiencies decreased with decreasing sampling flow rate. The combined evaluation of AtoA and AtoH efficiency provided more comprehensive performance indicators than either test alone. The experimental methodology presented here can facilitate the design and choice of aerosol sampler.

Real-Time Emission and Exposure Measurements of Multi-walled Carbon Nanotubes during Production, Power Sawing, and Testing of Epoxy-Based Nanocomposites.

ObjectivesThe use of manufactured nanomaterials is increasing globally. Although multi-walled carbon nanotubes (CNTs) are used in a wide range of applications, only limited data are available on emissions and exposures during CNT composite production. No exposure data using portable aethalometers in the personal breathing zone (PBZ) to monitor occupational exposure to CNTs have yet been published. The aim of this study was to characterize emissions of and exposures to CNTs during CNT composite production, sawing, and shear testing. We also investigated whether real-time aethalometer measurements of equivalent black carbon (eBC) could be used as a proxy filter sampling of elemental carbon (EC). The presence of CNTs as surface contamination in the production facility was monitored since this could contribute to airborne exposure.MethodsDuring CNT composite production in an industrial setting including both chemical and manufacturing laboratories, different work tasks (WTs) were studied with a combination of direct-reading instruments (aethalometer, aerodynamic particle sizer, condensation particle counter) and filter-based methods. Measurements were performed to monitor concentrations in the emission zone (EZ), PBZ, and background zone. The filter samples were analysed for EC and fibre concentration of CNTs using scanning electron microscopy (SEM). Additionally, surfaces in the facility were tape sampled for monitoring of CNT contamination, and analysed with SEM.ResultsClear eBC peaks were observed in the PBZ during several WTs, most clearly during open handling of CNT powder. Power sawing emitted the highest particle number concentration in the EZ of both nanoparticles and coarse particles, but no individual airborne CNTs, agglomerates, or aggregates were detected. Airborne CNTs were identified, for example, in a filter sample collected in the PBZ of a worker during mixing of CNT epoxy. The airborne CNT particles were large agglomerates which looked like porous balls in the SEM images. Significant EC exposures were found in the inhalable fraction while all respirable fractions of EC were below detection. The highest inhalable EC concentrations were detected during the composite production. No significant correlation was found between inhalable EC and eBC, most likely due to losses of large EC containing particles in the sampling lines and inside the eBC monitor. In total, 39 tape samples were collected. Surface contamination of CNTs was detected on eight surfaces in the chemical and manufacturing laboratories, mainly in the near-field zone. Elongated CNT-like features were detected in the sawdust after sawing of CNT composite.ConclusionsCharacterization of a workplace producing CNT composite showed that open handling of the CNT powder during weighing and mixing of CNT powder material generated the highest particle emissions and exposures. The portable direct-reading aethalometer provided time-resolved eBC exposure data with complementary information to time-integrated EC filter samples by linking peak exposures to specific WTs. Based on the results it was not possible to conclude that eBC is a good proxy of EC. Surface contamination of CNTs was detected on several surfaces in the near-field zone in the facility. This contamination could potentially be resuspended into the workplace air, and may cause secondary inhalation exposure.

A clinical observational analysis of aerosol emissions from dental procedures.

Aerosol generating procedures (AGPs) are defined as any procedure releasing airborne particles <5 μm in size from the respiratory tract. There remains uncertainty about which dental procedures constitute AGPs. We quantified the aerosol number concentration generated during a range of periodontal, oral surgery and orthodontic procedures using an aerodynamic particle sizer, which measures aerosol number concentrations and size distribution across the 0.5–20 μm diameter size range. Measurements were conducted in an environment with a sufficiently low background to detect a patient’s cough, enabling confident identification of aerosol. Phantom head control experiments for each procedure were performed under the same conditions as a comparison. Where aerosol was detected during a patient procedure, we assessed whether the size distribution could be explained by the non-salivary contaminated instrument source in the respective phantom head control procedure using a two-sided unpaired t-test (comparing the mode widths (log(σ)) and peak positions (DP,C)). The aerosol size distribution provided a robust fingerprint of aerosol emission from a source. 41 patients underwent fifteen different dental procedures. For nine procedures, no aerosol was detected above background. Where aerosol was detected, the percentage of procedure time that aerosol was observed above background ranged from 12.7% for ultrasonic scaling, to 42.9% for 3-in-1 air + water syringe. For ultrasonic scaling, 3-in-1 syringe use and surgical drilling, the aerosol size distribution matched the non-salivary contaminated instrument source, with no unexplained aerosol. High and slow speed drilling produced aerosol from patient procedures with different size distributions to those measured from the phantom head controls (mode widths log(σ)) and peaks (DP,C, p< 0.002) and, therefore, may pose a greater risk of salivary contamination. This study provides evidence for sources of aerosol generation during common dental procedures, enabling more informed evaluation of risk and appropriate mitigation strategies.

Use of Airway Replicas in Lung Delivery Applications.

The use of extrathoracic airway replicas in optimization of drug delivery to the lungs with nebulizers, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) is discussed. Such airway replicas have been useful in evaluating new pulmonary drug delivery platforms mainly based on the comparison of the total lung dose (TLD) and the aerodynamic particle size distribution (APSD) of the aerosol distal to the physical models. The ability of these in vitro methods to replicate in vivo results has allowed advancements in respiratory drug delivery and in the accuracy and utility of in vitro-in vivo correlations (IVIVCs).

Fine Particle Fraction: The Good and the Bad.

Fine particle fraction (FPF) is defined in general terms as the fraction or percentage of the drug mass contained in an aerosol cloud that may be small enough to enter the lungs and exert a clinical effect. An aerodynamic diameter of 5 μm represents the approximate border between "fine" and "coarse" particles, but there is no universally agreed upon definition of FPF in terms of an aerodynamic particle size range. FPF alone does not adequately describe a heterodisperse aerodynamic particle size distribution, and it needs to be combined with another measure or measures indicating the width of the distribution. When determined using techniques specified in United States and European Pharmacopeias, FPF is measured by cascade impactors that have straight-sided ninety degree inlets through which air is drawn at a constant rate. It is not the purpose of in vitro tests to predict in vivo behavior, and FPF is primarily a measure of aerosol quality. Despite this, FPF broadly predicts the amount of drug from an inhaler device depositing in the lungs, but it systematically overestimates whole lung deposition and may not correctly predict the relative lung depositions for two inhalers of different types. The relationship between FPF and both drug pharmacokinetics and clinical response is incompletely understood at the present time, and more studies are needed to investigate these relationships. Modifications to impactor technologies, including inlets that mimic the human extrathoracic airways and the use of realistic breathing patterns, would be expected to improve the predictive power of in vitro tests for drug delivery in vivo.

Characteristics of Particles and Debris Released after Implantoplasty: A Comparative Study.

Titanium particles embedded on peri-implant tissues are associated with a variety of detrimental effects. Given that the characteristics of these detached fragments (size, concentration, etc.) dictate the potential cytotoxicity and biological repercussions exerted, it is of paramount importance to investigate the properties of these debris. This study compares the characteristics of particles released among different implant systems (Group A: Straumann, Group B: BioHorizons and Group C: Zimmer) during implantoplasty. A novel experimental system was utilized for measuring and collecting particles generated from implantoplasty. A scanning mobility particle sizer, aerodynamic particle sizer, nano micro-orifice uniform deposit impactor, and scanning electron microscope were used to collect and analyze the particles by size. The chemical composition of the particles was analyzed by highly sensitive microanalysis, microstructures by scanning electron microscope and the mechanical properties by nanoindentation equipment. Particles released by implantoplasty showed bimodal size distributions, with the majority of particles in the ultrafine size range (<100 nm) for all groups. Statistical analysis indicated a significant difference among all implant systems in terms of the particle number size distribution (p < 0.0001), with the highest concentration in Group B and lowest in Group C, in both fine and ultrafine modes. Significant differences among all groups (p < 0.0001) were also observed for the other two metrics, with the highest concentration of particle mass and surface area in Group B and lowest in Group C, in both fine and ultrafine modes. For coarse particles (>1 µm), no significant difference was detected among groups in terms of particle number or mass, but a significantly smaller surface area was found in Group A as compared to Group B (p = 0.02) and Group C (p = 0.005). The 1 first minute of procedures had a higher number concentration compared to the second and third minutes. SEM-EDS analysis showed different morphologies for various implant systems. These results can be explained by the differences in the chemical composition and microstructures of the different dental implants. Group B is softer than Groups A and C due to the laser treatment in the neck producing an increase of the grain size. The hardest implants were those of Group C due to the cold-strained titanium alloy, and consequently they displayed lower release than Groups A and B. Implantoplasty was associated with debris particle release, with the majority of particles at nanometric dimensions. BioHorizons implants released more particles compared to Straumann and Zimmer. Due to the widespread use of implantoplasty, it is of key importance to understand the characteristics of the generated debris. This is the first study to detect, quantify and analyze the debris/particles released from dental implants during implantoplasty including the full range of particle sizes, including both micro- and nano-scales.