Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations

Darquenne, Chantal; Borojeni, Azadeh A.T.; Colebank, Mitchel J.; Forest, M. Gregory; Madas, Balázs G.; Tawhai, Merryn H.; Jiang, Yi

doi:10.3389/fphys.2022.923945

Cited by 14 publications

(7 citation statements)

References 106 publications

(133 reference statements)

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“…Furthermore, we also observed a significant size growth and tighter size distribution of the emitted particles as the device ages, which agrees with the measurements from a previous study that observed high particle concentration and submicron-sized particles in the ENDS-emitted aerosol [ 41 , 42 ]. In particular, increasing particle sizes with a narrower particle size distribution can enhance respiratory deposition and sedimentation rate of hazardous particle components within the ENDS aerosol [ 43 , 44 , 45 ]. For instance, our inhalation dosimetry analysis showed a significant increase in particle mass deposition and deposited surface area as the device ages, which is shown to be highly affected by changes in particle sizes and concentrations.…”

Section: Discussionmentioning

confidence: 99%

Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age

Jeon¹,

Zhang²,

Chepaitis³

et al. 2023

Toxics

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Electronic nicotine delivery systems (ENDS) aerosols are complex mixtures of chemicals, metals, and particles that may present inhalation hazards and adverse respiratory health risks. Despite being considered a safer alternative to tobacco cigarettes, metal exposure levels and respiratory effects associated with device aging and vaping frequency have not been fully characterized. In this study, we utilize an automated multi-channel ENDS aerosol generation system (EAGS) to generate aerosols from JUUL pod-type ENDS using tobacco-flavored e-liquid. Aerosol puff fractions (1–50) and (101–150) are monitored and sampled using various collection media. Extracted aerosols are prepared for metal and toxicological analysis using human primary small airway epithelial cells (SAEC). ENDS aerosol-mediated cellular responses, including reactive oxygen species (ROS), oxidative stress, cell viability, and DNA damage, are evaluated after 24 h and 7-day exposures. Our results show higher particle concentrations in later puff fractions (0.135 mg/m3) than in initial puff fractions (0.00212 mg/m3). Later puff fraction aerosols contain higher toxic metal concentrations, including chromium, copper, and lead, which elicit increased levels of ROS followed by significant declines in total glutathione and cell viability. Notably, a 30% increase in DNA damage was observed after 7 days because of later puff fraction exposures. This work is consistent with ENDS aerosols becoming more hazardous across the use of pre-filled pod devices, which may threaten respiratory health.

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Section: Discussionmentioning

confidence: 99%

Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age

Jeon¹,

Zhang²,

Chepaitis³

et al. 2023

Toxics

View full text Add to dashboard Cite

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“…Another plausible mechanism is through inhalation of infected droplets as considered in the present study. Residual inhaled droplets or those formed by aerosolisation of the infected mucosa (due to interaction of the infected mucosa with airflow) are subsequently transported from the nasopharynx deeper into the lung where they can release the viruses causing further infection ( Darquenne et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Another possibility is through inhalation of infected droplets, present in the nasopharynx, deeper into the LRT. These may be the droplets inhaled from the enivronment (which have not deposited in the URT), or those formed due to aerosolization of infected nasopharyngeal mucosa (ANM) ( Edwards et al., 2021 ; Darquenne et al., 2022 ). Hydrodynamic interaction between breathed air and the infected nasopharyngeal mucosa may cause the latter to aerosolize in certain conditions creating virus-laden aerosols/droplets ( Moriarty and Grotberg, 1999 ).…”

Section: Introductionmentioning

confidence: 99%

Inhalation of virus-loaded droplets as a clinically plausible pathway to deep lung infection

2023

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Respiratory viruses, such as SARS-CoV-2, preliminarily infect the nasopharyngeal mucosa. The mechanism of infection spread from the nasopharynx to the deep lung–which may cause a severe infection—is, however, still unclear. We propose a clinically plausible mechanism of infection spread to the deep lung through droplets, present in the nasopharynx, inhaled and transported into the lower respiratory tract. A coupled mathematical model of droplet, virus transport and virus infection kinetics is exercised to demonstrate clinically observed times to deep lung infection. The model predicts, in agreement with clinical observations, that severe infection can develop in the deep lung within 2.5–7 days of initial symptom onset. Results indicate that while fluid dynamics plays an important role in transporting the droplets, infection kinetics and immune responses determine infection growth and resolution. Immune responses, particularly antibodies and T-lymphocytes, are observed to be critically important for preventing infection severity. This reinforces the role of vaccination in preventing severe infection. Managing aerosolization of infected nasopharyngeal mucosa is additionally suggested as a strategy for minimizing infection spread and severity.

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“…The intricate geometry of the extra-thoracic that includes bends, expansions and constrictions leads to transition to turbulent airflows in the pharynx, larynx and trachea with Reynolds numbers on the order of several thousands (i.e., 2'000-10'000), depending on inhalation regimes [1][2][3][4]. Detailed modeling of these complex flows is required to determine the fate of particle-laden airflows and ensuing deposition patterns towards predicting for example pulmonary dosimetry [5] or the dispersion of airborne pathogen in the lungs [6,7].…”

Section: Introductionmentioning

confidence: 99%

In vitro–in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model

et al. 2023

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There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro–in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-ω SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1’500 to 7’000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro–in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints.

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Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations

Cited by 14 publications

References 106 publications

Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age

Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age

Inhalation of virus-loaded droplets as a clinically plausible pathway to deep lung infection

In vitro–in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model

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