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BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

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The dispersion of aerosols originating from one source, the 'index' passenger, within the cabin of the aircraft Do728 is studied experimentally using an aerosol-exhaling thermal manikin and in Reynolds-averaged Navier-Stokes simulations (RANS). The overall aim of the present study is the experimental determination of the aerosol spreading for the state-of-the-art mixing ventilation (MV) and to evaluate the potential of alternative ventilation concepts for controlling the aerosol spreading in RANS. For MV, the experiments showed that the ratio of inhaled to exhaled aerosol particles drops below 0.06% (volume ratio) for distances larger than two seat rows from the source. However, within a single row, the observed ratio is higher. Further, the dispersion is much weaker for a standing than for a seated index passenger. High air exchange rates and a well-guided flow prevent a dispersion of the aerosols in high concentrations over larger distances. Additionally, the positive effect of a mask and an increased air flow rate, and especially their combination are shown. In the complementary conducted RANS, the advantages of floor-based cabin displacement ventilation (CDV) which is alternative ventilation concept to MV, regarding spreading lengths and the dwell time of the aerosols in the cabin were determined. The obtained results also underline the importance of the flow field for the aerosol dispersion. Further, additional unsteady RANS (URANS) simulations of the short-term process of the initial aerosol cloud formation highlighted that the momentum decay of the breathing and the evaporation processes take place within a few seconds only. Supplementary Information: The online version contains supplementary material available at 10.1007/s13272-023-00644-3.

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Airborne transmission of disease is of concern in many indoor spaces. Here, aerosol dispersion and removal in an unoccupied 4-bed hospital room were characterized using a transient aerosol tracer experiment for 38 experiments covering 4 configurations of air purifiers and 3 configurations of curtains. NaCl particle (mass mean aerodynamic diameter ~3 µm) concentrations were measured around the room following an aerosol release. Particle transport across the room was 1.5-4 min which overlaps with the characteristic times for significant viral deactivation and gravitational settling of larger particles. Concentrations were close to spatially uniform except very near the source. Curtains resulted in a modest increase in delay and decay times, less so when combined with purifiers. The aerosol decay rate was in most cases higher than expected from the clean air delivery rate, but the reduction in steady-state concentrations resulting from air purifiers was less than suggested by the decay rates. Apparently, a substantial (and configuration-dependent) fraction of the aerosol is removed immediately, and this effect is not captured by the decay rate. Overall, the combination of curtains and purifiers is likely to reduce disease transmission in multi-patient hospital rooms.

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INTRODUCTION: Group singing has been associated with higher transmission risks via exhaled and spread aerosols in the CoVID19 pandemic. For this reason, many musical activities, such as rehearsals and lessons, but also voice therapy sessions, have been restricted in many countries. Consequently, transmission risks and pathways have been studied, such as aerosol amounts generated by exhalation tasks, convectional flows in rooms, or the impulse dispersion of different kinds of phonation. The use of water resistance exercises such as those utilizing LAX VOX®, are common in voice lessons and as vocal warm-ups. With this context, this study investigates the impulse dispersion characteristics of aerosols during a voiced water resistance exercise in comparison to normal singing. METHODS: Twelve professional singers (six male, six female) were asked to phonate a stable pitch through a silicone tube into a bottle filled with water, holding the end of the tube 5 cm below the surface. Before performing the tasks, the singers inhaled the vapor consisting of 0.5 L base liquid from an e-cigarette. The exhaled gas cloud coming out of the bottle was recorded in all three spatial directions and the dispersion was measured as a function of time. RESULTS: At the end of the phonation task, the median distance to the front was 0.55 m and the median of the lateral expansion of the cloud was 0.89 m, the maximum to the front reached 0.88 m, and the maximum of lateral expansion 1.05 m. For the upwards direction of the clouds a median of 1.00 m and a maximum of 1.34 m from the mouth were measured. Three seconds after the end of the task, the medians were declining. CONCLUSION: The exhaled aerosol cloud can expand despite the obstacle of the water when using LAX VOX® during phonation.

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In this work we compare the DNS results (Fabregat et al. 2021, Fabregat et al. 2021) for a mild cough already reported in the literarure with those obtained with a compressible URANS equations with a k-ϵ turbulence model. In both cases, the dispersed phase has been modelled as spherical Lagrangian particles using the one-way coupling assumption. Overall, the URANS model is capable of reproducing the observed tendency of light particles under 64 µm in diameter to rise due to the action of the drag exerted by the buoyant puff generated by the cough. Both DNS and URANS found that particles above 64 µm will tend to describe parabolic trajectories under the action of gravitational forces. Grid independence analysis allows to qualify the impact of increasing mesh resolution on the particle cloud statistics as flow evolves. Results suggest that the k-ϵ model overpredicts the horizontal displacement of the particles smaller than 64 µm while the opposite occurs for the particles larger than 64 µm.

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Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient's activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm2/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens).

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BACKGROUND: In the CoVID-19 pandemic, singing came into focus as a high-risk activity for the infection with airborne viruses and was therefore forbidden by many governmental administrations. OBJECTIVE: The aim of this study is to investigate the effectiveness of surgical masks regarding the spatial and temporal dispersion of aerosol and droplets during professional singing. METHODS: Ten professional singers performed a passage of the Ludwig van Beethoven's "Ode of Joy" in two experimental setups-each with and without surgical masks. First, they sang with previously inhaled vapor of e-cigarettes. The emitted cloud was recorded by three cameras to measure its dispersion dynamics. Secondly, the naturally expelled larger droplets were illuminated by a laser light sheet and recorded by a high-speed camera. RESULTS: The exhaled vapor aerosols were decelerated and deflected by the mask and stayed in the singer's near-field around and above their heads. In contrast, without mask, the aerosols spread widely reaching distances up to 1.3 m. The larger droplets were reduced by up to 86% with a surgical mask worn. SIGNIFICANCE: The study shows that surgical masks display an effective tool to reduce the range of aerosol dispersion during singing. In combination with an appropriate aeration strategy for aerosol removal, choir singers could be positioned in a more compact assembly without contaminating neighboring singers all singers.

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PURPOSE: The aim of this study was to compare aerosol exposure with or without an aerosol box in a pressurized/depressurized room during aerosol-generating procedures using an experimental model. METHODS: Cake flour (aerosol model) was expelled from an advanced life support training mannequin. The primary outcome measure was the number of 0.3-10 µm-sized particles at three locations corresponding to the physician, medical staff, and environmental aerosol exposure levels. The aerosol dispersion was visualized using a high-resolution video. The number of expelled particles was measured after artificial coughing during simulated tracheal intubation and extubation in four situations, with or without an aerosol box in a pressurized or depressurized room (≤ 2.5 Pa). RESULTS: The particles arising from tracheal intubation at the three positions in the four groups differed significantly in size (p < 0.05). The sizes of particles arising from extubation at the physicians' and medical staff's faces in the four groups differed significantly in size (p < 0.05). Post hoc analysis showed that the counts of all particles at the three positions were significantly lower in the depressurized room with an aerosol box than in the pressurized room without an aerosol box during tracheal intubation (p < 0.05 at three positions) and extubation (p < 0.05) at the physician's and medical staff's positions). Visual assessments supported these results. CONCLUSION: The aerosol box decreased the exposure of the aerosol to the physician, medical staff, and environment during aerosol-generating procedures in the depressurized room only.

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OBJECTIVE: To compare the effectiveness of different mask types in limiting the dispersal of coughed air. METHOD: The Schlieren method with a single curved mirror was used in this study. Coughed air has a slightly higher temperature than ambient air, which generates a refractive index gradient. A curved mirror with a radius of curvature of 10 m and a diameter of 60 cm was used. The spread of the cough wavefront was investigated among five subjects wearing: (1) no mask; (2) a single surgical mask; (3) a double surgical mask; (4) a cloth mask; (5) a valveless N95 mask; and (6) a valved N95 mask. RESULTS: All mask types reduced the size of the contaminated region significantly. The percentage reduction in the cross-sectional area of the contaminated region for the same mask types on different subjects revealed by normalized data suggests that the fit of a mask plays an important role. CONCLUSIONS: No significant difference in the spread of coughed air was found between the use of a single surgical mask or a double surgical mask. Cloth masks may be effective, depending on the quality of the cloth. Valved N95 masks exclusively protect the user. The fit of a mask is an important factor to minimize the contaminated region.

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The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections.

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Legionella bacteria can colonise and proliferate in water systems in the built environment and can be spread by aerosol generation. If inhaled by a susceptible individual, this can lead to respiratory infections such as Legionnaires' Disease (LD), or the generally milder Pontiac fever. Evaporative cooling systems (ECS), including cooling towers, used in industrial processes to dissipate excessive heat are prone to contamination by Legionella. From these systems it is possible for contaminated aerosols to be dispersed over a wide area, potentially exposing workers on site, neighbouring workplaces or nearby members of the public. Analysis of reported data on outbreaks of LD in Great Britain, collated for a ten year period, identified 44 separate legionellosis outbreaks of which seven were attributed to ECS and were responsible for 229 infections and 10 fatalities. This prompted an examination of health and safety inspection records which revealed, over a five year period, 321 enforcement actions taken against failings in Legionella control, of which 31% were attributed to cooling towers. Based on this evidence, an intervention programme was undertaken by health and safety inspectors in which 1,906 sites with ECS were inspected. During these inspections, sites were rated against four topics that are used to demonstrate compliance with statutory requirements for Legionella control: Risk Assessment; Written Control Scheme; Implementation of Control Scheme; and Record Keeping. While there was compliance at the majority of sites, breaches of the legislation were found at 625 sites (33% of those inspected), leading to 409 Improvement Notices (compelling dutyholders to make improvements to health and safety breaches of law in a given timeframe) and 12 Prohibition Notices (compelling dutyholders to stop work until they have remedied breaches in health and safety law) being served at 229 sites (12.0% of those inspected). Data from the intervention programme was analysed to identify root causes of these breaches of legislation on Legionella control. The majority of Improvement Notices (53%) were issued for the 'lack of effective implementation of a Written Control Scheme', with 'Risk Assessment' and 'Written Control Scheme' both accounting for 23%. More detailed examination showed major problems to be lack of training; failure to maintain the cleanliness of cooling towers and the water within them; risk assessments either being absent or not up to date, i.e., no longer representing the risks present; and Written Control Schemes being absent or insufficiently detailed. This provides a valuable data resource for dutyholders, so that they can understand where they need to focus to achieve significant improvement in legal compliance and therefore reduce the risk of LD for employees and members of the public affected by their workplace, and valuable data for regulators to target future interventions aimed at improving dutyholder compliance leading to better protection of workers and members of the public.

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The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 µm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system.

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