In vitro toxicological evaluation of aerosols generated by a 4th generation vaping device using nicotine salts in an air-liquid interface system.

BACKGROUND: Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface. METHODS: Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure. RESULTS: PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm². CONCLUSION: Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid.

Development of a protocol of isolation of nanoparticles from patients' broncho-alveolar lavages for their in vitro toxicity assessment.

To investigate potential correlations between human exposure to inhaled particles and pathological effects, the biological monitoring of nanoparticles in broncho-alveolar lavages (BAL) from patients has been proposed. To better understand the underlying mechanisms of toxicity, we propose to couple this biomonitoring of nanoparticles to their in vitro toxicity assessment. However, BAL obtained from regular clinical practice are conditioned with sodium hypochlorite solution (in a 50% v/v ratio), which is toxic to cells. The aim of this study was to develop a protocol to neutralize sodium hypochlorite, allowing to properly investigate the toxicity of the nanoparticles BAL contain. We first tried to neutralize chemically the sodium hypochlorite using H2O2, ascorbic acid or sodium ascorbate but this approach was unsuccessful. In addition, standard toxicology assays (MTT, LDH) could not be used because of interference with neutralizing solutions. We thus changed strategy and used ultracentrifugation to isolate nanoparticles from the sodium hypochlorite solution, with satisfactory extraction yields (88 to 100%). We then incubated the extracted nanoparticles with macrophages from the RAW264.7 cell line and assessed the cell viability and pro-inflammatory response. This study can be used as a proof-of-concept for further study of the biological impact of nanoparticles. This approach paves the way for studies aiming at a better understanding of the aetiology of some idiopathic diseases and underlying mechanisms.

Development of a Novel Bronchodilator Vaping Drug Delivery System Based on Thermal Degradation Properties.

This work aims to investigate bronchodilator delivery with the use of different vaping drug delivery systems (VDDS) by determining the dose equivalence delivered in relation to different references: a clinical jet nebulizer, a pMDI (pressurized metered dose inhaler) and a DPI (dry powder inhaler). Three different bronchodilators were used (terbutaline, salbutamol hemisulfate, ipratropium bromide). The e-liquids contained the active pharmaceutical ingredient (API) in powder form. Two different VDDS were tested (JUUL and a GS AIR 2 atomizer paired with a variable lithium-ion battery (i-stick TC 40 W), 1.5 ohm resistance, and 15 W power). Samples were collected using a glass twin impinger (GTI). High-performance liquid chromatography (HPLC) was used to quantify the drugs. A next-generation impactor (NGI) was used to measure the particle size distribution. Terbutaline emerged as the optimal API for bronchodilator delivery in both VDDS devices. It achieved the delivery of a respirable dose of 20.05 ± 4.2 µg/puff for GS AIR 2 and 2.98 ± 0.52 µg/puff for JUUL. With these delivered doses, it is possible to achieve a dose equivalence similar to that of a jet nebulizer and DPI, all while maintaining a reasonable duration, particularly with the GS AIR 2. This study is the first to provide evidence that vaping bronchodilators work only with appropriate formulation, vaping technology, and specific drugs, depending on their thermal degradation properties.

Biological effects of brake wear particles in mammalian models: A systematic review.

Road traffic is a major contributor to air pollution through aerosols both from exhaust emissions (EE) and non-exhaust emissions (NEE). NEE result from mechanical abrasion of brakes and tires, erosion of road surfaces and resuspension of road dust into the atmosphere by passing traffic. EE have been thoroughly studied and have decreased over time due to a stricter control. On the other hand, NEE have not received such attention and there is currently no legislation to specifically reduce NEE particles. Consequently, NEE relative part has become prevalent, potentially making of these emissions a major human health concern. The aim of this systematic review was to provide an overview of the current state of knowledge on the biological effects of brake wear particles, a type of NEE. To this end, we conducted a bibliographic search of two databases (PubMed and Web of Science) on June 1, 2023, focusing on the toxicological effects of brake wear particles induced in vitro and in vivo. We excluded reviews (no original experimental data), papers not written in English, studies performed in non-mammalian models and papers where no toxicity data were reported. Of the 291 papers, 19 were found to be relevant and included in our analysis, confirming that the assessment of the brake wear particles toxicity in mammalian models is still limited. This review also reports that brake wear particles can induce oxidative stress, proinflammatory response and DNA damage. Finally, some perspectives for further research and measures to mitigate the risk of brake wear emissions are discussed.

Can the impact of micro- and nanoplastics on human health really be assessed using in vitro models? A review of methodological issues.

Because of the many advantages they offer (strength, low cost, durability, lightweight, resistance, etc.), plastics are integral part of our daily life with a production constantly rising. However, their waste management is still inadequate, resulting in their release and accumulation in the environment, representing a main source of pollution. Their degradation results in debris of variable size including microplastics (0.1 µm-5 mm) and even nanoplastics (<0.1 µm), whose potential impact on ecosystems and human health have raised concerns. The potential adverse effects they may cause have been evaluated using both in vitro and in vivo models. However, due to some specific characteristics of micro- and nanoplastics, there are challenging questions about whether conventional in vitro tests are appropriate for evaluating their toxicity. For example, low-density plastics float on the surface of the culture medium and cannot come into contact with cells adhering to the bottom of the culture plates, which prevents proper evaluation of potential adverse effects and leads to misinterpretation of toxicological assays. In this review, we discuss the main issues related to the evaluation of micro- and nanoplastics toxicity using conventional in vitro assays. A literature survey has allowed to propose some solutions to circumvent these issues including the use of mathematical models to accurately determine the dose of particles delivered to cells, advanced 3D models (organoids), inverted cell culture models, cell cultures at the air-liquid interface or under dynamic conditions. Finally, we propose some perspectives and recommendations for further research on the in vitro evaluation of micro- and nanoplastics toxicity, underlining the importance of using standardized protocols for comparison purposes and samples and experimental conditions more representative of real-life exposure.

Advancements in acoustic drug delivery for paranasal sinuses: A comprehensive review.

Chronic rhinosinusitis (CRS) impacts patients' quality of life and healthcare costs. Traditional methods of drug delivery, such as nasal sprays and irrigation, have limited effectiveness. Acoustic Drug Delivery (ADD) using a nebulizer offers targeted delivery of drug to the sinuses, which may improve the treatment of CRS. This review examines the influence of aerosol particle characteristics, aero-acoustic parameters, inlet flow conditions, and acoustic waves on sinus drug delivery. Key findings reveal that smaller particles improve the ADD efficiency, whereas larger sizes or increased density impair it. The oscillation amplitude of the air plug in the ostium is crucial for the ADD efficiency. Introducing acoustic waves at the NC-sinus system's resonance frequency improves aerosol deposition within sinuses. Future research should address advanced models, optimizing particle characteristics, investigating novel acoustic waveforms, incorporating patient-specific anatomy, and evaluating long-term safety and efficacy. Tackling these challenges, ADD could offer more effective and targeted treatments for sinus-related conditions such as CRS.

Impact of gas humidification and nebulizer position under invasive ventilation: preclinical comparative study of regional aerosol deposition.

Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 cm to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99mtechnetium-labeled diethylene-triamine-penta-acetic acid. Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions are more likely to cause peripheral deposition of aerosols in the lungs. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification.

Acoustic Aerosol Delivery: Assessing of Various Nasal Delivery Techniques and Medical Devices on Intrasinus Drug Deposition.

This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99mTc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2-3; respectively 0.03 ± 0.007% vs. 0.003 ± 0.0002% in the right maxillary sinus and 0.027 ± 0.006% vs. 0.013 ± 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition.

Impact of e-cigarette experimentation and use on smoking behavior among adolescents aged 15-16 years in the Loire department, France.

INTRODUCTION: We describe the vaping and smoking habits of French adolescents aged 15-16 years in the Loire department with a view to assess the impact of e-cigarette experimentation and use on their smoking behavior. METHODS: This quantitative, cross-sectional, single-center and observational study conducted from January to July 2019 targeted 6622 students aged 15-16 years attending public high school in the Loire department, France. RESULTS: A total of 4937 (74.6%) adolescents were included. Of these, 73.2% were non-vapers and 72.2% non-smokers; 66.0% of adolescents were non-vapers and non-smokers. Slightly less than half of adolescents had experimented with e-cigarettes (44.6%), more than half of whom (26.8%) continued to use vaping products, with 6.02% vaping daily. Likewise, a little less than half of adolescents had experimented with smoked tobacco (42.4%), more than half of whom (27.8%) continued to use smoking products, with 10.3% smoking daily. Vapers and smokers (20.6%) tended to begin with the use of smoked tobacco and to progress to the dual use of vaping and smoked tobacco products. Vaping had a positive effect, as 71.8% of vapers who smoked tobacco before initiating vaping stopped or reduced smoking following their progression to this double use. More than half of tobacco users are daily users while this daily use affects only 1/3 boys and 1/6 girls for vape. Finally, nearly 80.7% of adolescents who had never smoked before vaping did not smoke at the time of the study. CONCLUSIONS: Our data suggest that vaping has a rather marginal impact on smoking initiation among French adolescents aged 15-16 years in the Loire department. They therefore neither confirm nor completely disprove the gateway effect theory, relating to use of tobacco subsequent to vaping.

Regional French evolution of tobacco and e-cigarette experimentation and use among adolescents aged 15-16 years: A cross-sectional observational study conducted in the Loire department from 2018 to 2020.

Background: We assessed/compared the evolution of tobacco and e-cigarette experimentation and use among French adolescents of the Loire department aged 15-16 years. Methods: A descriptive, cross-sectional/observational study conducted in 2018-2020 among 7,950 Year 11 pupils attending 27 public secondary schools of the Loire department, France. Results: From 2018 to 2020, 66.18% of adolescents were "non-vapers and non-smokers", 19.76% were "vapers and smokers", 7.90% were "non-vapers and smokers" and 6.15% were "vapers and non-smokers". E-cigarette experimentation was more prevalent than tobacco experimentation (44.92% vs 41.67%), and daily vaping was less prevalent than daily smoking (5.40% vs 10.24%). More boys than girls were daily vapers or daily smokers. A decrease was observed in tobacco experimentation (from 41.22% in 2018 to 39.73% in 2020) and e-cigarette experimentation (from 50.28% in 2018 to 41.25% in 2020). Current vaping remained stable, with an increase in daily vaping. French adolescent vapers frequently use e-liquids with little or no nicotine or with fruit or sweet flavours. Conclusions: Adolescents used e-cigarettes mainly for experimental and/or recreational purposes, with no intention of progression to daily smoking. Although the design of this study is not longitudinal and caution must be exercised, from our cross-sectional observational study data, it appears that the proportion of "non-vapers and non-smokers" tended to increase. "Smokers" tended to progress to the dual use of vaping and smoked tobacco, with the likely intention to reduce or quit smoking.

Biological effects of Tire and Road Wear Particles (TRWP) assessed by in vitro and in vivo studies - A systematic review.

Air quality is a critical issue because even small amounts of air pollutants can cause significant adverse health effects. Road traffic is a major contributor to air pollution both through aerosols from exhaust emissions (EE) and non-exhaust emissions (NEE). The latter result from mechanical abrasion of brakes and tires, erosion of road surfaces and resuspension of road dust into the atmosphere by passing traffic. EE have been extensively characterized and have declined over time due to mitigation measures. By contrast, NEE have been less studied, are not tightly regulated and there are limited data on their toxicity. Thus, NEE relative part has become prevalent, potentially making of these emissions a major human health concern. The aim of this systematic review was to provide an overview of the current state of knowledge on the biological effects of NEE. We paid particular attention to the toxicological effects of Tire and Road Wear Particles (TRWP) induced in vitro and in vivo in mammalian models. To this end, we performed a bibliographic search in two databases (PubMed and Web of Science). Of the 400 papers, 22 were found to be relevant and included in our analysis, confirming that the assessment of the TRWP toxicity in mammalian models is still limited. This review also reports that oxidative stress and inflammation are the main mechanisms underlying the toxicity of TRWP.

Filtration efficiency of medical and community face masks using viral and bacterial bioaerosols.

Face masks are often recommended in community settings to prevent the airborne transmission of respiratory viruses or bacteria. Our first objective was to develop an experimental bench to assess the viral filtration efficiency (VFE) of a mask with a methodology similar to the normative measurement of bacterial filtration efficiency (BFE) used to determine the filtration performance of medical masks. Then, using three categories of masks of increasing filtration quality (two types of community masks and one type of medical mask), filtration performances measured ranged from 61.4 to 98.8% of BFE and from 65.5 to 99.2% of VFE. A strong correlation (r = 0.983) between bacterial and viral filtration efficiency was observed for all types of masks and for the same droplets size in the 2-3 µm range. This result confirms the relevance of the EN14189:2019 standard using bacterial bioaerosols to evaluate mask filtration, to also extrapolate mask performances whatever their filtration quality against viral bioaerosols. Indeed, it appears that the filtration efficiency of masks (for micrometer droplet sizes and low bioaerosol exposure times) depends mainly on the size of the airborne droplet, rather than on the size of the infectious agent contained in that droplet.

Assessing of low-tech solutions for aerosol delivery: Comparative performance study of manufactured versus homemade spacers.

PURPOSE: This study aims to evaluate the performance of low-cost homemade spacers compared with manufactured valved holding chambers (VHCs) for fluticasone propionate delivery via a pMDI (pressurized Metered Dose Inhaler). METHODS: The Total Emitted Dose (TED) and particle size distribution were measured for pMDI alone or connected to the different spacers, according to CAN/CSA-Z264.1-02 standard. Two types of low-cost alternative and manufactured spacers were investigated: 500 mL plastic bottle and 553 mL aluminium can; non-antistatic plastic VHCs and aluminium antistatic VHCs. RESULTS: The TED of homemade plastic bottle vs plastic VHC were similar in the 20-23% range. In contrast, the TED of homemade aluminium can was higher compared to aluminium VHC (83% vs 68%). The Fine Particle Fraction (FPF) was similar for the two plastic-based spacers (in the 12.68-17.60% range), although it was greater for the aluminium can compared to aluminium VHC (51% vs 42%). However, all spacers have limited large particles fraction, mainly deposited in the oropharyngeal tract, potentially decreasing side effects. CONCLUSION: We demonstrated that low-tech solutions as homemade spacers have at least similar performances to VHC medical devices composed of same material (aluminium or plastic). Thus, low-cost homemade spacers represent alternatives in case of emergency and without VHCs nearby.

Évolution des comportements tabagique et de vapotage d'adolescents français de 15 à 18 ans (2018-2020).

Introduction : Longitudinal studies make it possible to study the evolution of a class of individuals over time. However, they are rarely used in France to observe the same population of young adolescents according to their grade level over the course of several years.Purpose of research : Based on the longitudinal monitoring of repeated annual cross-sectional studies on young adolescents (from 15 to 18 years old) conducted at the Honoré d’Urfé public high school (Saint-Étienne, Loire, France) involving 336 10th grade pupils in 2018, 360 11th grade pupils in 2019 and 273 12th grade pupils in 2020, we observed and studied students’ smoking and vaping behavior over a period of three years.Results : Between the ages of 15 and 18 years, the prevalence of tobacco experimentation increased almost linearly (39.10%, 47.50%, and 53.11%), while the prevalence of ‘non-smoking’ decreased by 4.5%. In addition, the prevalence of e-cigarette experimentation was stable (46.38%, 49.44%, 47.62%), whereas the prevalence of daily vaping increased by 5.0%.Conclusions : The prevalence of tobacco experimentation tends to increase with age and to catch up with that of e-cigarette experimentation, which remains stable at this stage of adolescence. Introductions to these two products seem to be rather recreational, playful, and experimental in nature, and do not have a significant connection with the development of their daily use or propensity to addiction.

Considerations on dosimetry for in vitro assessment of e-cigarette toxicity.

Electronic cigarettes (or e-cigarettes) can be used as smoking cessation aid. Some studies tend to show that they are less hazardous than tobacco cigarettes, even if it does not mean they are completely safe. The huge variation in study designs assessing in vitro toxicity of e-cigarettes aerosol makes it difficult to make comparisons and draw robust and irrefutable conclusions. In this paper, we review this heterogeneity (in terms of e-cigarette products, biological models, and exposure conditions) with a special focus on the wide disparity in the doses used as well as in the way they are expressed. Finally, we discuss the major issue of dosimetry and show how dosimetry tools enable to align data between different exposure systems or data from different laboratories and therefore allow comparisons to help further exploring the risk potential of e-cigarettes.

Characterization of the elemental and particle load of patient exhaled breath condensate and comparison with pulmonary lavages.

In the field of biomonitoring, exhaled breath condensate (EBC) is described as a potentially useful matrix for assessing inhalation exposure biomarkers in a non-invasive way. However, it is still unclear to what extent EBC is representative of the deep lung. To address this knowledge gap, EBC, bronchial washes (BWs), and bronchoalveolar lavages (BALs) were collected from 82 patients suffering from interstitial lung diseases (ILDs). The particulate contents and elemental composition of EBC, BW, and BAL were then compared in the same patients. The size distribution of particles in EBC was assessed with dynamic light scattering while inductively coupled plasma mass spectrometry was used to quantify its elemental composition. In addition, transmission electron microscopy coupled with energy dispersive x-ray spectrometry were used to further characterize samples of interest. EBC was found to be representative of both the sub-micron and nano-sized particle fractions of BAL and BW, with lower overall levels of elements in EBC than in BW and BAL. Silicon (Si) was the main component for all respiratory matrices with median levels of 2525µg l-1, 5643µg l-1and 5169µg l-1in the nano/ion fractions of EBC, BAL and BW, respectively. Moreover, Si levels in EBC from patients in this study were elevated compared to the levels reported in the literature for healthy subjects. Interestingly, Si levels in the EBC of ILD patients were inversely related to those in BAL and BW. In conclusion, the particulate content of EBC is associated with the lung particle burden and potentially correlates with pathologies, rendering it a relevant biomonitoring technique for the occupational and clinical fields.

In Vitro Biological Effects of E-Cigarette on the Cardiovascular System-Pro-Inflammatory Response Enhanced by the Presence of the Cinnamon Flavor.

The potential cardiovascular effects of e-cigarettes remain largely unidentified and poorly understood. E-liquids contain numerous chemical compounds and can induce exposure to potentially toxic ingredients (e.g., nicotine, flavorings, etc.). Moreover, the heating process can also lead to the formation of new thermal decomposition compounds that may be also hazardous. Clinical as well as in vitro and in vivo studies on e-cigarette toxicity have reported potential cardiovascular damages; however, results remain conflicting. The aim of this study was to assess, in vitro, the toxicity of e-liquids and e-cigarette aerosols on human aortic smooth muscle cells. To that purpose, cells were exposed either to e-liquids or to aerosol condensates obtained using an e-cigarette device at different power levels (8 W or 25 W) to assess the impact of the presence of: (i) nicotine, (ii) cinnamon flavor, and (iii) thermal degradation products. We observed that while no cytotoxicity and no ROS production was induced, a pro-inflammatory response was reported. In particular, the production of IL-8 was significantly enhanced at a high power level of the e-cigarette device and in the presence of the cinnamon flavor (confirming the suspected toxic effect of this additive). Further investigations are required, but this study contributes to shedding light on the biological effects of vaping on the cardiovascular system.

Technical features of vaping drug delivery system for bronchodilator delivery.

PURPOSE: Several technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). METHODS: Terbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). RESULTS: GS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. CONCLUSION: We proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

Impact of washing parameters on bacterial filtration efficiency and breathability of community and medical facemasks.

Can medical face masks be replaced by reusable community face masks with similar performance? The influence of the number of wash cycles, the wash temperature and the use of detergent was evaluated on the performance of one medical face masks (MFM) and ten community face masks (CFM). The performance of the new and washed masks was characterized from the bacterial filtration efficiency (BFE) and the differential pressure (DP). The tests on the new masks showed that the MFM had always better BFE than CFMs. Although two of the CFMs showed a BFE value exceeding 95%, only one can be classified as type I MFM based on both BFE and DP requirements. The influence of the washing parameters was investigated on the MFM and these two CMFs with excellent BFE properties. The parameters had no effect on the BFE of CFMs whilst the MFM exhibited a loss in efficiency when washed with detergent. The DP of masks were not impacted by the washing. The results clearly show that even though a compromise has to be made between the BFE and breathability, it seems possible to manufacture CFMs with performances similar to a type I MFM, without achieving type II requirements.

Toward Better Characterization of a Free-Base Nicotine Fraction in e-Liquids and Aerosols.

Given that nicotine salts are a growing market, methods are needed to characterize nicotine forms in e-cigarette vaping products. By lowering the free-base nicotine fraction (αfb) in favor of protonated forms, the addition of organic acids to the e-liquid mix greatly modulates nicotine pharmacokinetics and improves vapers' craving. This research investigated (1) the performance of pH measurement, liquid-liquid extraction (LLE), and acid/nicotine molar ratio calculation methods for αfb estimation in 6 nicotine benzoate and nicotine salicylate e-liquids and (2) nicotine protonation in the aerosol post vaporization. Aerosols were generated with a JUUL device and another mod-pod on a vaping machine to assess device effects. E-liquid and aerosol samples were then analyzed after further analytical optimization of previous methods and careful consideration of biases. Globally, performances were comparable between methods. αfb accounted for less than 5% of nicotine content regardless of experimental conditions. αfb were consistent between e-liquids and aerosols irrespective of e-cigarette devices. Hence, e-liquids are adequate surrogates for aerosols, facilitating the establishment of regulations. pH measurement is one of the most used methods and enables the establishment of relative scales for e-liquid classification but lacks automation possibility. Until now, the extent of sample dilution remained arbitrary. The dilution factor was fixed at 10, as usually achieved, since no effect of dilution was noted. pH values ranged from 5.3 to 6.3 in accordance with the literature. By contrast, LLE relies on the specificity of organic solvent for free-base nicotine extraction, causing discrepancies in previous studies. Here, the results were similar to αfb values from pH determination. Yet, LLE presented the highest variability and was the most time-consuming protocol. Finally, αfb calculation from molar ratio was the most robust and versatile method. Estimations can be made in silico from reported composition data and/or after liquid chromatography routine analysis.