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Respiratory Tract Deposition of E‐Cigarette Particles

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Abstract

Total and regional deposition of inhaled electronic cigarette (E‐cig) particles in the respiratory tract (RT) depends on both physical properties of the inhaled particles and biological factors of users, for example, breathing pattern or puff profile, airway anatomy, and regional ventilation. Accurate particle sizing of E‐cig aerosols is essential for predicting particle deposition in the RT. Studies using a variety of sizing methods have shown mass median aerodynamic diameters ranging from 0.2 to 1.2 um and secondary count diameters in the ultrafine range (<0.1 μm). Incorporating these particle sizes into a multiple‐path particle dosimetry (MPPD) model shows 10% to 45% total lung deposition by mass and 30% to 80% for ultrafine particles depending on the breathing patterns. These predictions are consistent with experimental measures of deposition fraction of submicron and ultrafine particles. While box‐mod‐type E‐cig devices allow for full “direct‐lung” inhalations of aerosol, the more recent pod‐based, and disposable E‐cigs (e.g., JUUL, Puff Bar, Stig) deliver the aerosol as a “mouth‐to‐lung” puff, or bolus, that is inhaled early in the breath followed to various degrees by further inhalation of ambient air. Measurement of realistic ventilation patterns associated with these various devices may further improve deposition predictions. Finally, while in vivo measures of RT deposition present a challenge, a recent methodology to radiolabel E‐cig particles may allow for such measurements by gamma scintigraphy. Supported by NIH/NHLBI R01HL139369. © 2022 American Physiological Society. Compr Physiol 12: 3823–3832, year.

Figure 1. Figure 1. Effect of humidity and PG/VG content on particle size (MMAD) from a Sigelei 213 W TC/Uwell Crown 2 tank measured by low flow Sierra cascade impaction.
Figure 2. Figure 2. Average puff profiles (flow rate vs. time) for four adult vapers using the JUUL E‐cigarette. (AUC = area under the curve)
Figure 3. Figure 3. Lifeshirt (respiratory inductance plethysmography) profile for a single inhalation from an E‐cig device (VaporShark DNA 250 TC box‐mod/SMOK TFV8 tank; 80 W power setting).
Figure 4. Figure 4. Predicted intrathoracic deposition of 1 μm diameter particles for a 750 mL tidal volume at 15 breaths per minute in Weibel's symmetric morphology scaled to a lung volume of 3375 mL. The respiratory tract regions are designated as bronchi, bronchioles, and parenchyma and refer to generations 1 to 8, 9 to 16, and 17 to 23, respectively. Adapted from Bennett and Brown 2005 4.
Figure 5. Figure 5. Calculated deposition fractions, for different pauses (BHT) and flow rates, using ARA software 1. The MMAD is 0.75 μm for all combinations. Adapted from Sundahl et al. 2017 (37)
Figure 6. Figure 6. Average deposition efficiency of five subjects for mouth‐breathing as function of particle diameter, the bars indicate the variation of individual deposition, broken lines: computed curves. Adapted from Heyder et al. 1975 17.
Figure 7. Figure 7. Posterior gamma camera images from a healthy subject of a Xe133 equilibrium scan (left) and a deposition scan for deep inhalation of 1 μm aerosol (center). Right shows the central/peripheral (C/P) analysis of deposition images. Adapted from Bennett et al. 2002 5.
Figure 8. Figure 8. Mass and radioactivity cascade impactor measurements of the unlabeled and radiolabeled E‐cig grouped into seven particle size bins. Adapted from Holbrook et al. 2019 20.


Figure 1. Effect of humidity and PG/VG content on particle size (MMAD) from a Sigelei 213 W TC/Uwell Crown 2 tank measured by low flow Sierra cascade impaction.


Figure 2. Average puff profiles (flow rate vs. time) for four adult vapers using the JUUL E‐cigarette. (AUC = area under the curve)


Figure 3. Lifeshirt (respiratory inductance plethysmography) profile for a single inhalation from an E‐cig device (VaporShark DNA 250 TC box‐mod/SMOK TFV8 tank; 80 W power setting).


Figure 4. Predicted intrathoracic deposition of 1 μm diameter particles for a 750 mL tidal volume at 15 breaths per minute in Weibel's symmetric morphology scaled to a lung volume of 3375 mL. The respiratory tract regions are designated as bronchi, bronchioles, and parenchyma and refer to generations 1 to 8, 9 to 16, and 17 to 23, respectively. Adapted from Bennett and Brown 2005 4.


Figure 5. Calculated deposition fractions, for different pauses (BHT) and flow rates, using ARA software 1. The MMAD is 0.75 μm for all combinations. Adapted from Sundahl et al. 2017 (37)


Figure 6. Average deposition efficiency of five subjects for mouth‐breathing as function of particle diameter, the bars indicate the variation of individual deposition, broken lines: computed curves. Adapted from Heyder et al. 1975 17.


Figure 7. Posterior gamma camera images from a healthy subject of a Xe133 equilibrium scan (left) and a deposition scan for deep inhalation of 1 μm aerosol (center). Right shows the central/peripheral (C/P) analysis of deposition images. Adapted from Bennett et al. 2002 5.


Figure 8. Mass and radioactivity cascade impactor measurements of the unlabeled and radiolabeled E‐cig grouped into seven particle size bins. Adapted from Holbrook et al. 2019 20.
References
 1.Applied Research Associates Inc. MPPD: Multiple‐Path Particle Dosimetry Model. https://www.ara.com/mppd/
 2.Asgharian B, Hofmann W, Bergmann R. Particle deposition in a multiple‐path model of the human lung. Aerosol Sci Technol 34 (4): 332‐339, 2001.
 3.Bake B, Wood L, Murphy B, Macklem PT, Milic‐Emili J. Effect of inspiratory flow rate on regional distribution of inspired gas. J Appl Physiol 37: 8‐17, 1974.
 4.Bennett WD, Brown JS. Particulate dosimetry in the respiratory tract. In: Foster WM, Costa DL, editors. Air Pollutants and the Respiratory Tract. New York, NY: Marcel Dekker, Inc., 2005.
 5.Bennett WD, Brown JS, Zeman KL, Hu SC, Scheuch G, Sommerer K. Targeting delivery of aerosols to different lung regions. J Aerosol Med 15: 179‐188, 2002.
 6.Bennett WD, Scheuch G, Zeman KL, Brown JS, Kim C, Heyder J, Stahlhofen W. Regional deposition and retention of particles in shallow, inhaled boluses: Effect of lung volume. J Appl Physiol 86: 168‐173, 1999.
 7.Bennett WD, Zeman KL. Effect of race on fine particle deposition for oral and nasal breathing. Inhal Toxicol 17 (12): 641‐648, 2005.
 8.Bennett WD, Zeman KL, Kim CS. Variability of fine particle deposition in healthy adults: Effect of age and gender. Am J Respir Crit Care Med 153 (5): 1641‐1647, 1996.
 9.Brand P, Rieger C, Schulz H, Beinert T, Heyder J. Aerosol bolus dispersion in healthy subjects. Eur Respir J 10 (2): 460‐467, 1997.
 10.Brown JS, Kim CS, Reist P, Zeman KL, Bennett WD. Generation of radiolabelled “soot‐like” ultrafine aerosols suitable for use in human inhalation studies. Aerosol Sci Technol 32: 325‐337, 2000.
 11.Brown JS, Zeman KL, Bennett WD. Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am J Respir Crit Care Med 166: 1240‐1247, 2002.
 12.Chamberlain MJ, Morgan WKC, Vinitski S. Factors influencing the regional deposition of inhaled particles in man. Clin Sci 64: 69‐78, 1983.
 13.Darquenne C, Brand P, Heyder J, Paiva M. Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests. J Appl Physiol 83 (3): 966‐974, 1997.
 14.Farsalinos K, Poulas K, Voudris V. Changes in puffing topography and nicotine consumption depending on the power setting of electronic cigarettes. Nicotine Tob Res 20 (8): 993‐997, 2018.
 15.Grant BJ, Jones HA, Hughes JM. Sequence of regional filling during a tidal breath in man. J Appl Physiol 37 (2): 158‐165, 1974.
 16.Hensel EC, Eddingsaas NC, DiFrancesco AG, Jayasekera S, O'Dea S, Robinson RJ. Framework to estimate total particulate mass and nicotine delivered to E‐cig users from natural environment monitoring data. Sci Rep 9: 8752, 2019.
 17.Heyder J, Armbruster L, Gebhart J, Grein E, Stahlhofen W. Total deposition of aerosol particles in the human respiratory tract for nose and mouth breathing. J Aerosol Sci 6: 311‐328, 1975.
 18.Heyder JJ, Gebhart J, Rudolf G, Schiller CF, Stahlhofen W. Deposition of particles in the human respiratory tract in the size range 0.005–15 μm. J Aerosol Sci 17 (5): 811‐882, 1986.
 19.Hinds WC. Aerosol Technology: Properties, Behavior and Measurement of Airborne Particles (2nd ed). New York: John Wiley & Sons, Inc., 1999, p. 379‐385.
 20.Holbrook LT, Zeman KL, Burke A, Jaspers I, Bennett WD. Radiolabeling an electronic cigarette aerosol using technetium carbon ultrafine particles. J Aerosol Med Pulm Drug Deliv 32 (1): 47‐53, 2019.
 21.Ingebrethsen BJ, Cole SK, Alderman SL. Electronic cigarette aerosol particle size distribution measurements. Inhal Toxicol 24 (14): 976‐984, 2012.
 22.Jaques PA, Kim CS. Measurement of total lung deposition of inhaled ultrafine particles in healthy men and women. Inhal Toxicol 12: 715‐731, 2000.
 23.Kane DB, Li W. Particle size measurement of electronic cigarette aerosol with a cascade impactor. Aerosol Sci Technol 55 (2): 205‐214, 2021.
 24.Kim CS, Hu SC, DeWitt P, Gerrity TR. Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J Appl Physiol 81 (5): 2203‐2213, 1996.
 25.Kim CS, Jaques PA. Respiratory dose of inhaled ultrafine particles in healthy adults. Philos Trans R Soc London, Ser A 358 (1775): 2693‐2705, 2000.
 26.Martonen TB, Katz IM. Deposition patterns of aerosolized drugs within human lungs: Effects of ventilatory parameters. Pharm Res 10 (6): 871‐878, 1993.
 27.Mikheev VB, Brinkman MB, Granville CA, Gordon SM, Clark PI. Real‐time measurement of electronic cigarette aerosol size distribution and metals content analysis. Nicotine Tob Res 18: 1895‐1902, 2016.
 28.Mikheev VB, Ivanov A, Lucas EA, South PL, Colijn HO, Clark PI. Aerosol size distribution measurement of electronic cigarette emissions using combined differential mobility and inertial impaction methods: Smoking machine and puff topography influence. Aerosol Sci Technol 52 (11): 1233‐1248, 2018.
 29.Miller FJ, Asgharian B, Schroeter JD, Price OT. Improvements and additions to the Multiple Path Particle Dosimetry model. J Aerosol Sci 99: 14‐26, 2016.
 30.National Academies of Sciences, Engineering, and Medicine. In: Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E‐Cigarettes. Washington, DC: National Academies Press, 2018.
 31.National Institute for Public Health and the Environment (RIVM). Multiple Path Particle Dosimetry Model (MPPD v 1.0): A Model for Human and Rat Airway Particle Dosimetry. Bilthoven, The Netherlands. RIVA Report 650010030, 2002.
 32.Newman S, Bennett WD, Biddiscombe M, Devadason SG, Dolovich MB, Fleming J, Haeussermann S, Kietzig C, Kuehl PJ, Laube BL, Sommerer K, Taylor G, Usmani OS, Zeman KL. Standardization of techniques for using planar (2D) imaging for aerosol deposition assessment of orally inhaled products. J Aerosol Med Pulm Drug Deliv 25 Suppl 1: S10‐S28, 2012.
 33.Oldham MJ, Zhang J, Rusyniak MJ, Kane DB, Gardner WP. Particle size distribution of selected electronic nicotine delivery system products. Food Chem Toxicol 113: 236‐240, 2018.
 34.Robinson RJ, Hensel EC, Al‐Olayan AA, Nonnemaker JM, Lee YO. Effect of e‐liquid flavor on electronic cigarette topography and consumption behavior in a 2‐week natural environment switching study. PLoS One 13 (5): e0196640, 2018.
 35.Robinson RJ, Hensel EC, Morabito PN, Roundtree KA. Electronic cigarette topography in the natural environment. PLoS One 10 (6): e0129296, 2015.
 36.Robinson RJ, Hensel EC, Roundtree KA, Difrancesco AG, Nonnemaker JM, Lee YO. Week long topography study of young adults using electronic cigarettes in their natural environment. PLoS One 11 (10): e0164038, 2016.
 37.Sundahl M, Berg E, Svensson M. Aerodynamic particle size distribution and dynamic properties in aerosols from electronic cigarettes. J Aerosol Sci 103: 141‐150, 2017.
 38.Trajan M, Logus JW, Enns EG, Man SFP. Relationship between regional ventilation and aerosol deposition in tidal breathing. Am Rev Respir Dis 130: 64‐70, 1984.
 39.Weibel ER. Morphometry of the Human Lung. Berlin: Springer‐Verlag, 1963.

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How to Cite

William D. Bennett, Phillip W. Clapp, Landon T. Holbrook, Kirby L. Zeman. Respiratory Tract Deposition of E‐Cigarette Particles. Compr Physiol 2022, 12: 3823-3832. doi: 10.1002/cphy.c210038