Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

Impact of dry intrusion events on the composition and mixing state of particles during the winter Aerosol and Cloud Experiment in the Eastern North Atlantic (ACE-ENA)

Long-range transport of continental emissions has a far-reaching influence over remote regions, resulting in substantial change in the size, morphology, and composition of the local aerosol population and cloud condensation nuclei (CCN) budget. Here, we investigate the physicochemical properties of atmospheric particles collected on board a research aircraft flown over the Azores during the winter 2018 Aerosol and Cloud Experiment in the Eastern North Atlantic (ACE-ENA) campaign. Particles were collected within the marine boundary layer (MBL) and free troposphere (FT) after long-range atmospheric transport episodes facilitated by dry intrusion (DI) events. Chemical and physical properties of individual particles were investigated using complementary capabilities of computer-controlled scanning electron microscopy and X-ray spectromicroscopy to probe particle external and internal mixing state characteristics. Furthermore, real-time measurements of aerosol size distribution, cloud condensation nuclei (CCN) concentration, and back-trajectory calculations were utilized to help bring into context the findings from offline spectromicroscopy analysis. While carbonaceous particles were found to be the dominant particle type in the region, changes in the percent contribution of organics across the particle population (i.e., external mixing) shifted from 68 % to 43 % in the MBL and from 92 % to 46 % in FT samples during DI events. This change in carbonaceous contribution is counterbalanced by the increase in inorganics from 32 % to 57 % in the MBL and 8 % to 55 % in FT. The quantification of the organic volume fraction (OVF) of individual particles derived from X-ray spectromicroscopy, which relates to the multi-component internal composition of individual particles, showed a factor of 2.06 ± 0.16 and 1.11 ± 0.04 increase in the MBL and FT, respectively, among DI samples. We show that supplying particle OVF into the κ-Köhler equation can be used as a good approximation of field-measured in situ CCN concentrations. We also report changes in the κ values in the MBL from κMBL, non-DI=0.48 to κMBL, DI=0.41, while changes in the FT result in κFT, non-DI=0.36 to κFT, DI=0.33, which is consistent with enhancements in OVF followed by the DI episodes. Our observations suggest that entrainment of particles from long-range continental sources alters the mixing state population and CCN properties of aerosol in the region. The work presented here provides field observation data that can inform atmospheric models that simulate sources and particle composition in the eastern North Atlantic.

Modeled Respiratory Tract Deposition of Aerosolized Oil Diluents Used in Δ9-THC-Based Electronic Cigarette Liquid Products

Electronic cigarette, or vaping, products (EVP) heat liquids (“e-liquids”) that contain substances (licit or illicit) and deliver aerosolized particles into the lungs. Commercially available oils such as Vitamin-E-acetate (VEA), Vitamin E oil, coconut, and medium chain triglycerides (MCT) were often the constituents of e-liquids associated with an e-cigarette, or vaping, product use-associated lung injury (EVALI). The objective of this study was to evaluate the mass-based physical characteristics of the aerosolized e-liquids prepared using these oil diluents. These characteristics were particle size distributions for modeling regional respiratory deposition and puff-based total aerosol mass for estimating the number of particles delivered to the respiratory tract. Four types of e-liquids were prepared by adding terpenes to oil diluents individually: VEA, Vitamin E oil, coconut oil, and MCT. A smoking machine was used to aerosolize each e-liquid at a predetermined puff topography (volume of 55 ml for 3 s with 30-s intervals between puffs). A cascade impactor was used to collect the size-segregated aerosol for calculating the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). The respiratory deposition of EVP aerosols on inhalation was estimated using the Multiple-Path Particle Dosimetry model. From these results, the exhaled fraction of EVP aerosols was calculated as a surrogate of secondhand exposure potential. The MMAD of VEA (0.61 μm) was statistically different compared to MCT (0.38 μm) and coconut oil (0.47 μm) but not to Vitamin E oil (0.58 μm); p < 0.05. Wider aerosol size distribution was observed for VEA (GSD 2.35) and MCT (GSD 2.08) compared with coconut oil (GSD 1.53) and Vitamin E oil (GSD 1.55). Irrespective of the statistical differences between MMADs, dosimetry modeling resulted in the similar regional and lobular deposition of particles for all e-liquids in the respiratory tract. The highest (~0.08 or more) fractional deposition was predicted in the pulmonary region, which is consistent as the site of injury among EVALI cases. Secondhand exposure calculations indicated that a substantial amount of EVP aerosols could be exhaled, which has potential implications for bystanders. The number of EVALI cases has declined with the removal of VEA; however, further research is required to investigate the commonly available commercial ingredients used in e-liquid preparations.

Assessing the potential efficacy of marine cloud brightening for cooling Earth using a simple heuristic model

A simple heuristic model is described to assess the potential for increasing solar reflection by augmenting the aerosol population below marine low clouds, which nominally leads to increased cloud droplet concentration and albedo. The model estimates the collective impact of many point source particle sprayers, each of which generates a plume of injected particles that affects clouds over a limited area. A look-up table derived from simulations of an explicit aerosol activation scheme is used to derive cloud droplet concentration as a function of the sub-cloud aerosol size distribution and updraft speed, and a modified version of Twomey's formulation is used to estimate radiative forcing. Plume overlap is accounted for using a Poisson distribution, assuming idealized elongated cuboid plumes that have a length driven by aerosol lifetime and wind speed, a width consistent with satellite observations of ship track broadening, and a depth equal to an assumed boundary layer depth. The model is found to perform favorably against estimates of brightening from large eddy simulation studies that explicitly model cloud responses to aerosol injections over a range of conditions. Although the heuristic model does not account for cloud condensate or coverage adjustments to aerosol, in most realistic ambient remote marine conditions these tend to augment the Twomey effect in the large eddy simulations, with the result being a modest underprediction of brightening in the heuristic model. The heuristic model is used to evaluate the potential for global radiative forcing from marine cloud brightening as a function of the quantity, size, and lifetime of salt particles injected per sprayer and the number of sprayers deployed. Radiative forcing is sensitive to both the background aerosol size distribution in the marine boundary layer into which particles are injected and the assumed updraft speed. Given representative values from the literature, radiative forcing sufficient to offset a doubling of carbon dioxide ΔF2×CO2 is possible but would require spraying 50 % or more of the ocean area. This is likely to require at least 104 sprayers to avoid major losses of particles due to near-sprayer coagulation. The optimal dry diameter of injected particles, for a given salt mass injection rate, is 30–60 nm. A major consequence is that the total salt emission rate (50–70 Tg yr−1) required to offset ΔF2×CO2 is a factor of five lower than the emissions rates required to generate significant forcing in previous studies with climate models, which have mostly assumed dry diameters for injected particles in excess of 200 nm. With the lower required emissions, the salt mass loading in the marine boundary layer for ΔF2×CO2 is dominated by natural salt aerosol, with injected particles only contributing ∼ 10 %. When using particle sizes optimized for cloud brightening, the aerosol direct radiative forcing is shown to make a minimal contribution to the overall radiative forcing.

A New Instrument for Determining the Coarse-Mode Sea Salt Aerosol Size Distribution

Sea salt aerosol(s) (SSA) play a significant role in the atmosphere through aerosol direct and indirect effects, and in atmospheric chemistry as a source of tropospheric bromine. In-situ measurements of coarse-mode SSA particles are limited because of their low concentration and relatively large sizes (dry radius, rd > 0.5 μm). With this in mind, a new, low-cost, easily usable method for sampling coarse-mode SSA particles in the marine boundary layer was developed. A SSA particle sampler that uses an impaction method was designed and built using 3D printing and Arduino microcontrollers and sensors. It exposes polycarbonate slides to ambient airflow remotely on a kite-based platform to capture coarse-mode SSA particles. Because it is a smaller version of the Giant Nucleus Impactor (GNI), designed for use on aircraft, it is named the miniature-Giant Nucleus Impactor, or “mini-GNI”. After sample collection, the same optical microscope methodology utilized by the GNI was used to analyze the wetted salt particles that impacted onto the slides. In this proof-of-concept study, multiple mini-GNIs were attached serially to a kite string, allowing for sampling at multiple altitudes simultaneously. The robustness of the results from this new instrument and methodology for sampling at ambient RH (~ 75 %) the SSA particle size distribution with rd > 3.3 μ m are compared with a similar study. We find that the SSA particle number concentration decreases weakly with altitude and shows no correlation to instantaneous U10 wind speed along the windward coastline of O‘ ahu in the Hawaiian Islands.

Aerosol formation and growth rates from chamber experiments using Kalman smoothing

Bayesian state estimation in the form of Kalman smoothing was applied to differential mobility analyser train (DMA-train) measurements of aerosol size distribution dynamics. Four experiments were analysed in order to estimate the aerosol size distribution, formation rate, and size-dependent growth rate, as functions of time. The first analysed case was a synthetic one, generated by a detailed aerosol dynamics model and the other three chamber experiments performed at the CERN CLOUD facility. The estimated formation and growth rates were compared with other methods used earlier for the CLOUD data and with the true values for the computer-generated synthetic experiment. The agreement in the growth rates was very good for all studied cases: estimations with an earlier method fell within the uncertainty limits of the Kalman smoother results. The formation rates also matched well, within roughly a factor of 2.5 in all cases, which can be considered very good considering the fact that they were estimated from data given by two different instruments, the other being the particle size magnifier (PSM), which is known to have large uncertainties close to its detection limit. The presented fixed interval Kalman smoother (FIKS) method has clear advantages compared with earlier methods that have been applied to this kind of data. First, FIKS can reconstruct the size distribution between possible size gaps in the measurement in such a way that it is consistent with aerosol size distribution dynamics theory, and second, the method gives rise to direct and reliable estimation of size distribution and process rate uncertainties if the uncertainties in the kernel functions and numerical models are known.

Impact of Dry Intrusion Events on Composition and Mixing State of Particles During Winter ACE-ENA Study

Long-range transport of continental emission has far reaching influence over remote regions resulting in substantial change in the size, morphology, and composition of the local aerosol population and cloud condensation nuclei (CCN) budget. Here, we investigate the physiochemical properties of atmospheric particles collected onboard a research aircraft flown over the Azores during the winter 2018 Aerosol and Cloud Experiment in the Eastern North Atlantic (ACE-ENA) campaign. Particles were collected within the marine boundary layer (MBL) and free troposphere (FT), after long-range atmospheric transport episodes facilitated by dry intrusion (DI) events. Chemical and physical properties of individual particles were investigated using complementary capabilities of computer-controlled scanning electron microscopy and X-ray spectro-microscopy to probe particle external and internal mixing state characteristics in the context of real-time measurements of aerosol size distribution, cloud condensation nuclei (CCN) concentration, and back trajectory calculations. While carbonaceous particles were found to be the dominant particle-type in the region, changes in the percent contribution of organics across the particle population (i.e., external mixing) shifted from 68 % to 43 % in the MBL and from 92 % to 46 % in FT samples during DI events. This change in carbonaceous contribution is counterbalanced by the increase of inorganics from 32 % to 57 % in the MBL and 8 % to 55 % in FT. The quantification of organic volume fraction (OVF) of individual particles derived from X-ray spectro-microscopy, which relates to the multi-component internal composition of individual particles, showed a factor of 2.06 ± 0.16 and 1.11 ± 0.04 increase in the MBL and FT, respectively, among DI samples. We show that supplying particle OVF into the κ-Köhler equation can be used as a good approximation of field measured in-situ CCN concentrations. We also report changes in the κ values between κMBL, non-DI = 0.48 to κMBL, DI = 0.41 and κFT, non-DI = 0.36 to κFT, DI = 0.33, which is consistent with enhancements in OVF followed by the DI episodes. Our observations suggest that entrainment of particles from long-range continental sources alters the mixing state population and CCN properties of aerosol in the region. The work presented here provides field observation data that can inform atmospheric models that simulate sources and particle composition in the Eastern North Atlantic.

Factors affecting aerosol size distribution during various dental procedures

Objectives: To determine the impact of various aerosol mitigation interventions and establish duration of aerosol persistence in a variety of dental clinic configurations. Methods: We performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (e.g, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies [ventilation and high-volume evacuation (HVE)] and prevalence of particulate matter in the dental clinic environment before, during and after high-speed drilling, slow speed drilling and ultrasonic scaling procedures. Results: Conical and ISOVAC HVE were superior to standard tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics, regardless of configuration, when conical and ISOVAC HVE were used. Conclusions: Dentists should consider using conical or ISOVAC HVE rather than standard tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients as aerosols are rapidly dispersed. Clinical Significance: ISOVAC HVE is highly effective in reducing aerosol emissions. With adequate ventilation and HVE use, dental fallow time can be reduced to 5 minutes.