- Email: [email protected]
A polydisperse aerosol inhalation system designed for human studies
Aerosol Science 33 (2002) 1433 – 1446 www.elsevier.com/locate/jaerosci
A polydisperse aerosol inhalation system designed for human studies Jacky A. Rosatia; ∗ , James S. Brownb , Thomas M. Petersa , David Leitha , Chong S. Kimc a
Department of Environmental Sciences and Engineering, University of North Carolina, CB# 7431, 104 Rosenau Hall, Chapel Hill, NC, 27599-7431, USA b Center for Environmental Medicine and Lung Biology, Chapel Hill, NC, USA c U.S. EPA National Health and Environmental E-ects Research Laboratory, Human Studies Division, Chapel Hill, NC, USA Received 14 January 2002; received in revised form 28 May 2002; accepted 29 May 2002
Abstract A polydisperse aerosol inhalation system has been developed to measure particle deposition in the lungs of human subjects. Nebulizers are used to generate aerosols with mass median aerodynamic diameters from 0.3 to 3 m, and geometric standard deviations of 1.8–2.0. Inspired aerosol is drawn from a holding bag, passes through a sliding valve and a pneumotachograph, and enters a heated mouthpiece. Exhaled aerosol passes from the mouthpiece and pneumotachograph, through a second sliding valve and is collected in a heated sample bag. Inhalation and exhalation valves trigger automatically with change in 8ow direction through the pneumotachograph. Complete size distributions of inhaled and exhaled aerosol are measured by an aerodynamic particle sizer and a scanning mobility particle sizer. Fractional particle deposition of a test aerosol in the lung is determined by comparing inhaled and exhaled aerosol size fractions. Total deposition is determined from the sum of the fractional depositions. This new system precludes the need for monodisperse aerosol series to simulate polydisperse aerosol data, thus substantially reducing both study length and subject exposure. ? 2002 Elsevier Science Ltd. All rights reserved. Keywords: Polydisperse aerosol; Inhalation; Deposition
1. Introduction Although deposition of monodisperse aerosols in the human lung has been extensively investigated, few data are available on the deposition of polydisperse aerosols. The deposition of polydisperse ∗
Corresponding author. Tel.: +1-919-966-0632; fax: +1-919-966-6367. E-mail address: [email protected] (J.A. Rosati).
0021-8502/02/$ - see front matter ? 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 0 2 1 - 8 5 0 2 ( 0 2 ) 0 0 0 8 7 - 3
1434
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
aerosols is important because aerosols in ambient and occupational settings are polydisperse (James et al., 1996, Chap. 10) and these aerosols have been associated with adverse health eAects (Dockery et al., 1993; Dockery & Pope, 1994). Recent studies suggest airborne particulate matter, at concentration levels below present US National Ambient Air Quality Standards and United Kingdom PM-10 workplace regulations, negatively aAect human health and worker productivity (Utell & Frampton, 1995; MacNee & Donaldson, 1999, Chap. 30; Wark & Warner, 1981). Due to the lack of polydisperse data, deposition of a series of monodisperse aerosols in the human lung has been used to simulate polydisperse aerosol deposition in modeling (Diu & Yu, 1983; Ferron, Karg, & Peter, 1993). Use of this method assumes that particle interactions in the human lung from coagulation and scavenging will be negligible provided that aerosol concentrations are suGciently low (Diu & Yu, 1983). Whether this is truly the case, and whether interactive forces beyond coagulation and scavenging are present in the human lung remains a question. The present paper describes a method to directly measure the deposition of polydisperse aerosols in the human lung. While the aerosol delivery system used in this method is similar to those used previously, older systems are limited in their aerosol measurement ability. Most traditional systems determine only total deposition of monodisperse aerosols using a photometer or laser, although some have looked at total deposition of polydisperse aerosols using a laborious Ilter method, and others have analyzed only the aerosol’s ultraIne fraction (Davies, Heyder, & Subba Ramu, 1972; Heyder, Gebhart, Heigwer, Roth, & Stahlhofen, 1973; Wanner, Brodnan, Perez, Henke, & Kim, 1985; Wilson, Hiller, Wilson, & Bone, 1985). The current system can measure the complete size distribution of both an inhaled and exhaled polydisperse aerosol from 0.015 to 15:4 m. It can determine both the total deposition of an inhaled aerosol as well as the fractional deposition of multiple particle sizes within this aerosol. Use of this new method would preclude the need to use a series of monodisperse aerosols to simulate a polydisperse aerosol in modeling, would account for particle interactions, would allow inhalation studies to be conducted more rapidly, and by doing so, would substantially reduce human subject exposure during studies. 2. Methods and setup Fig. 1 is a schematic of the apparatus used, which can be broken into three components: the aerosol generation system, the inhalation system, and the aerosol measurement system. 2.1. Aerosol generation system Polydisperse aerosol is generated using a three-jet Collison nebulizer (BGI, Inc., Waltham, MA) and DeVilbiss Model 40 Glass nebulizer (Sunrise Medical, Somerset, PA). Nebulizers were chosen based on generated aerosol size. The Collison nebulizer produces wet droplets with a maximum mass median aerodynamic diameter (MMAD) of 2 m and a geometric standard deviation (GSD) of 1.8–2.0 at an air 8ow of 7:1 lpm and operating pressure of 20 psi. The DeVilbiss nebulizer produces wet droplets with a maximum MMAD of 4:2 m and a GSD of 1.8–2:0 at an air 8ow of 11 lpm and operating pressure of 10 psi (John, 1993, Chap. 5). For testing purposes, non-hygroscopic di-2-ethylhexyl sebacate was nebulized. Solutions were prepared by dissolving sebacate in ethyl
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 Mouthpiece & Pneumotach Pressure Transducer Outlet Valve
Signal Modulation & Data Acquisition
1435
Compressed Air
Inlet Valve DataRam Nebulizer
Heated Exhale Bag
Inhale Bag
Neutralizer
Three-way Valve
SMPS APS
Dilution Air In & Vacuum Air Out of Mixing Chambers
Fig. 1. Schematic of polydisperse aerosol generation and measurement system designed for human studies.
alcohol. Final particle size is dependent on the maximum wet droplet size of the nebulizer and the cube root of the solute-to-solvent concentration. The Collison nebulizer, with solute-to-solvent concentrations of 0.3% and 13%, was used to generate sebacate aerosols with MMADs of 0.3 and 1:0 m, respectively. The DeVilbiss nebulizer, with a solute-to-solvent concentration of 36%, was used to generate sebacate aerosol with a MMAD of 3:0 m. A syringe pump (Harvard Apparatus, Millis, MA) provides a constant feed of solution to the nebulizers to minimize the change in solution concentration due to solvent evaporation and thus, minimize the change in generated particle size. A three-stage dilution system is used to reduce the concentration of the aerosol to levels acceptable for a human exposure study (less than 2 mg=m3 ). Nebulized aerosol enters a 2l mixing chamber and a portion of the aerosol is removed with a vacuum system. The remainder of the aerosol is diluted with Iltered air and proceeds through two additional chambers where the process is repeated. After the Inal dilution, sampling with a Drager pump (Drager, Germany) found ethyl alcohol to be non-detectable. From the dilution process, aerosol proceeds through a Kr-85 charge neutralizer (TSI, Inc., St. Paul, MN) before entering the inhalation bag.
1436
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
2.2. Inhalation system The subject breathes through a removable, Te8on-covered brass mouthpiece while following a computer-generated breathing pattern. As a breath is drawn, a pneumatically controlled three-way slide valve opens (Hans Rudolph, Kansas City, MO) and aerosol enters the heated mouthpiece from a 25 l latex rubber bag. This bag ensures that the subject has enough aerosol to breathe at all times, even when aerosol 8ow is lower than the inhaled 8ow. On expiration, the inhalation valve closes and a second slide valve opens, directing exhaled aerosol into a second 25 l latex rubber bag that is housed in a heated plexiglass box. This exhalation bag accumulates approximately 15 –20 l of ◦ exhaled aerosol for sampling. Heating the bag and surrounding box to 38 C (body temperature) prevents condensation of water vapor, thus reducing loss of aerosol to the interior walls of the bag. Dessicant packs that line the bag serve to dry the aerosol before it passes through a diAusion dryer and into the sampling equipment. Prior to each test, the exhalation bag is 8ushed with clean air and put under a vacuum to remove residual air. Inspiratory and expiratory 8ows are measured by a Fleisch No. 1 pneumotachograph. Flow resistance through the pneumotachograph corresponds to pressure drop, which is converted to voltage by a pressure transducer (Model 239, Setra Systems, Acton, MA) and then relayed to an analog-to-digital converter (Model 2801A, Data Translation, Marlboro, MA) in a desktop computer. The 8ow data are acquired at 40 Hz and analyzed using ASYST software (ASYST Software Technologies, Rochester, NY). This software was also used to calibrate the 8ow and volume through the pneumotachograph and to open and close the slide valves. The program allows the triggering of inlet and outlet slide valves with change in 8ow direction through the pneumotachograph. When the inlet valve opens, the outlet valve closes and vice versa to avoid re-inhalation of exhaled air. The program also generates a desired breathing pattern for a subject to follow on the computer screen. This program can be modiIed to accommodate various tidal volumes (TV), 8ow rates, and breath holds. Furthermore, this software tracks the length of time from initial inhalation to APS and SMPS sampling, as well as the total volume exhaled into the bag. 2.3. Aerosol measurement system A DataRam (MIE, Inc., Billerica, MA) continuously measures the aerosol concentration at the outlet of the inhalation bag to ensure that inhaled aerosol concentration is suGciently low for human subject studies, i.e. less than 2 mg=m3 . The DataRam, a light scattering device used to determine total mass concentration of aerosols, was calibrated for each test aerosol using gravimetric Ilter samples. To determine fractional deposition, inhaled and exhaled aerosol is measured with an aerodynamic particle sizer (APS) (Model 3310, TSI, Inc., St. Paul, MN) and a scanning mobility particle sizer (SMPS) consisting of an electrostatic classiIer (Model 3071, TSI, Inc., St. Paul, MN) and a condensation particle counter (Model 3022, TSI, Inc., St. Paul, MN). The APS measures particles with a diameter ¿ 0:7 m while the SMPS is used for particles ¡ 0:7 m. The APS samples at 5 lpm, with 1 lpm of aerosol 8ow and 4 lpm of sheath air. A 60-s sample is used, and APS size limits were set to range from 0.75 to 15:399 m. The SMPS samples at 0:3 lpm through an impactor with a 0:508 mm diameter oriIce. At these operating conditions, the impactor provides a 50% cut size of 0:808 m, which eliminates larger particles that can distort the measured particle size distribution.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1437
For a given sample 8ow, size limits of the SMPS are governed by sampling time. Using 60-s upscan and 30-s downscan, the measurable SMPS size range is 14.9 –700 nm. The data from both the APS and SMPS are then merged to provide a complete size distribution. A three-way manual valve (Hans Rudolph, Kansas City, MO) is used to control the aerosol sampling location. Prior to each run, the valve is oriented to sample aerosol at the outlet of the inhalation bag (Fig. 1). After a suGcient volume of respired air is collected in the exhalation bag, the valve is switched so that exhaled aerosol is sampled directly from the middle of the heated bag. 2.4. Validation and optimization of data from the APS and SMPS The sizing accuracy of the APS and SMPS systems was validated using aerosolized monodisperse polystyrene latex (PSL) spheres (Duke ScientiIc Corp., Palo Alto, CA) from 0.2 to 5 m in diameter. PSL spheres in deionized water were nebulized using a Retec Medical Nebulizer (Retec=DeVilbiss, Somerset, PA), dried by passing through a diAusion dryer, and sampled from a small chamber by the APS and SMPS. Calibration curves were developed by comparing the APS and SMPS data to the PSL sphere sizes. The complete aerosol distribution, developed from merged APS and SMPS data, was validated using a Sierra 210 Cascade Impactor (Anderson Instruments Inc., Smyrna, GA) and an InTox Impactor (InTox, Albuquerque, NM) operated at 5 and 10 lpm, respectively. The InTox impactor was operated at a higher 8ow rate to achieve cut sizes less than 1 m. Impactor 8ows were calibrated prior to testing with a Gilibrator Primary Standard Air8ow Calibrator (Gilian Instrument Corp, Wayne, NJ). Impactors were used to validate the aerosol distribution because they directly measure mass, and are generally considered a ‘primary standard’ for measuring aerosol mass size distributions. Polydisperse aerosol was generated using a Collison nebulizer. Nebulized aerosol was routed to a mixing chamber where it was sampled by the APS, SMPS, Sierra 210, and InTox concurrently. Four sampling runs were performed to ensure precision of the measurements and merging technique. For all tests, the aerosol concentration was kept between 1 and 2 mg=m3 , the level at which subjects will be exposed. Sampling time was approximately 180 min to collect suGcient mass on the impactor substrates and Ilter for gravimetric analysis. APS and SMPS samples were taken consecutively at 5-min intervals, and runs were averaged by bin to provide a single time-averaged size distribution that could be directly compared to the impactor measurements. The data merging method was optimized by trial and error to maximize agreement between the data sets. 2.5. System removal e;ciencies Particle loss, , was determined for each part of the inhalation system. Here, varies with particle diameter and represents the fraction of an incoming aerosol that collects in the part of the system in question. DiAerent sized monodisperse test aerosols were run through each part of the inhalation system. Concentration was measured using two calibrated DataRams—one upstream and one downstream of the system part evaluated. Removal eGciency could then be determined from =1−Cdown =Cup , where Cdown represents downstream concentration and Cup represents that upstream. Fig. 2 shows each sampling location in the inhalation system.
1438
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 Mouthpiece & Pneumotach
Sampling Position #2 (conc #2)
Exhaled Aerosol = CB
Sampling Position #1 (conc #1) Inlet Aerosol = CA
Heated Exhalation Bag
Inhalation Bag
Definition of Losses or Efficiencies: η 1= 1-(conc #2/conc #1) η 2= 1-(conc #3/conc #2) η 3= 1-(conc #3/conc #1)
Aerosol
Three-way Valve Sampling Position #3 (conc #3) Classifier & CPC APS
Fig. 2. DeInition of system removal eGciencies, 1 , 2 and 3 , and sampling locations in the inhalation system. CA = concentration of inlet aerosol into the system and CB = concentration of aerosol exhaled at mouthpiece, both as measured by the APS and SMPS. Sampling locations (denoted by crosses) represent placement of DataRams during loss testing.
Particle deposition eGciency in the lung can then be calculated by Eq. (1) Deposition eGciency = 1 − =1−
Exhaled particle concentration Inhaled particle concentration CB (1 − 3 ) ; CA (1 − 1 )(1 − 2 (t))
(1)
where CA is the concentration of inlet aerosol into the system as measured by the APS and SMPS, CB is the concentration of aerosol exhaled at mouthpiece as measured by the APS and SMPS, 1 is the loss for inlet line, inlet valve, and mouthpiece, 2 (t) is the time-dependent loss for outlet lines, outlet valve, exhalation bag and diAusion dryer, 3 is the loss for sampling line from inlet to APS and SMPS, and, 1 − is the recovery, or particles that are not deposited in the sample lines. As aerosols are collected in the exhalation bag for a number of breaths, preliminary studies indicate that the aerosol may remain in the bag for up to 5 min before sampling with the APS and SMPS. 2 (t) losses were determined for 0 –5 min bag holding times allowing the appropriate correction to be applied based on residence time in the bag prior to APS and SMPS sampling.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1439
2.6. Preliminary testing Two types of preliminary testing were performed. First, the new polydisperse aerosol inhalation system was tested against an existing, photomoter-based system (Kim & Hu, 1998; Kim, Hu, DeWitt, & Gerrity, 1996) using monodisperse aerosols. Second, the new inhalation system was tested with polydisperse aerosols to compare the deposition of monodisperse particles to the deposition of discrete sections of the polydisperse aerosol. The new inhalation system was tested against the photometer system using a Harvard Pump (Harvard Apparatus, Millis, MA) to simulate breathing. Monodisperse sebacate particles (1 and 3 m) were produced by a monodisperse aerosol generator (MAGE) (Lavoro E Ambiente, Bologna, Italy). Aerosol concentration was approximately 3 mg=m3 for each system. The concentration was high enough to provide stable signals for the photometer system, and low enough to minimize coincidence error in the APS and SMPS system. Stainless-steel screens were placed in a Ilter holder prior to the Harvard Pump. Screen mesh size was varied to achieve the desired level of deposition for each particle size tested. The pump was set to ‘breathe’ with a tidal volume of 0:75 l and a 8ow rate of 250 ml=s. Aerosol was ‘inhaled’ and ‘exhaled’ by the pump on each system, and deposition for each aerosol size was determined. Nine or more runs were performed for each particle size at both a high and low deposition levels. Deposition for the two systems was then compared for each particle size using a paired t-test. To compare monodisperse particle deposition with discrete sections of polydisperse aerosol deposition, a polydisperse aerosol with an MMAD of 3 m and GSD of 2.0 was generated, and the Harvard Pump was set up with the same parameters as the above experiment. Again, nine runs were performed at both a high and low deposition levels. Deposition data for the monodisperse particles were then compared to the deposition of discrete sections of the polydisperse aerosol, i.e. 3 m bin from APS and SMPS data, using a paired t-test. 3. Results and discussion 3.1. Validation of data from the APS and SMPS The sizing accuracy of the APS and SMPS system was validated using aerosolized polystyrene latex (PSL) spheres. Several sphere diameters were used, and data for the actual sizes as determined by the manufacturer are plotted versus the measured size in Fig. 3. Error bars that represent one standard deviation are not visible in the Igure because the error was so small (less than 2%). Comparisons of the size distribution of a polydisperse aerosol measured simultaneously with the APS and SMPS system and two diAerent cascade impactors are presented in Figs. 4a and b. The data were compared as mass concentration frequencies to account for diAerences in sample mass between the three instruments in Fig. 4a. Presentation of the data in this form shows reasonably good agreement between the instruments, with some discrepancies between the impactor and APS and SMPS data. The SMPS overestimated aerosol concentration between 0.3 and 0:6 m when compared to the cascade impactors, and the APS underestimated aerosol concentration between 0.7 and 1:9 m when compared to the impactors. Such discrepancies between the SMPS, APS and cascade impactors were expected because each instrument uses a diAerent measurement technique
1440
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 6.0
Measured Average PSL DP, µm
1:1 Line 5.0
SMPS APS
4.0
3.0
2.0
1.0
0.0 0.0
1.0
2.0
3.0
4.0
5.0
6.0
Actual PSL Dp, µm
Fig. 3. Diameter of PSL spheres measured with the APS and SMPS system compared to size reported by the manufacturer.
and has diAerent measurement error. In addition, error is introduced during the conversion from number count into mass of particles. As respiratory deposition is determined by the ratio of exhaled to inhaled aerosol for each particle size, these discrepancies should pose no signiIcant problems. The similarity in the cumulative mass size distributions (MMAD = 1:12 ± 0:08 and GSD = 1:98 ± 0:05) presented in Fig. 4b suggests that the discrepancies have a minimal eAect on size distribution. 3.2. System removal e;ciencies System losses () were determined for several diAerent size particles. Figs. 5 and 6 show percent recovery, 1 − 1 and 1 − 3 , as a function of particle size for sebacate oil aerosol. Recovery data were It to a curve and the curve’s equation (given on the Igure) was used for raw APS and SMPS data correction. All curves It had an R2 value of 0.96 or greater. Fig. 7 shows changes in recovery, 1 − 2 (t), for each particle size as a function of residence time in the exhalation bag. Fig. 8 shows recovery as a function of aerosol size for an exhalation bag=line hold time of 3 min. Again, recovery data were It to a curve, and the curve’s equation was used to correct raw APS and SMPS data. The R2 value of each curve was 0.99 or greater. 3.3. Comparison of new system to photometer-based system The loss correction equations and the new inhalation system were validated against a pre-existing photometer system. Deposition values for 3 m particles on the new system and the photometer-based system were 7:86% ± 5:84 and 7:74% ± 0:37, respectively, for a low deposition condition. For a high deposition condition, values for 3 m particles on the new system and the photometer-based system were 69:17% ± 2:99 and 72:67% ± 0:52, respectively. Paired t-tests found no signiIcant diAerence in the corrected deposition data acquired by the new system and the photometer-based system for 3 m particles. Deposition values for 1 m particles on the new system and on the photometer-based system were 22.0% ± 0:39 and 19:5% ± 0:13, respectively, for a low deposition condition. For a
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1441
1.60 Sierra Impactor
Mass Concentration Frequency
1.40
Intox Impactor
1.20
APS & SMPS Merged Data
1.00 0.80 0.60 0.40 0.20 0.00 0.10
1.00 Particle Diameter, µm
(a)
10.00
10
Particle Size, µm
Intox Sierra APS & SMPS
1
(b)
0.9999
0.999
0.99
0.9
0.95
0.2 0.3 0.4 0.5 0.6 0.7 0.8
0.1
0.05
0.01
0.001
0.0001
0.1
Cumulative Mass Probability Less Than Indicated Particle Size
Fig. 4. (a) Mass frequency plot of merged APS and SMPS sampling data compared to sampling data for two types of cascade impactor. (b) Cumulative distribution plot of merged APS and SMPS sampling data, as well as sampling data for two types of cascade impactor. MMAD and GSD comparable for all sampling instruments.
high deposition condition, values for 1 m particles on the new system and the photometer-based system were 63:20% ± 0:97 and 62:14% ± 0:21, respectively. Although t-tests yielded a signiIcant diAerence in the deposition data acquired by the two systems for 1 m particles, this diAerence was less than 1% and was deemed unimportant. Figs. 9a and b show mean values with standard error bars for monodisperse 1 and 3 m particles, respectively, at high and low deposition levels. The
1442
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 120
Recovery, %
100 80 2
y = -0.6114x - 2.1986x + 99.833 2 R = 0.963
60 40 20 0 0.0
1.0
2.0
3.0
4.0
5.0
Particle Diameter, µm
Fig. 5. Percent recovery (1 − 1 ) from inlet line, inlet valve, and mouthpiece by particle size. 120
Recovery, %
100 80
2
y = -2.895x + 6.8131x + 97.416 2 R = 0.9979
60 40 20 0 0.0
1.0
2.0 3.0 Particle Diameter, µm
4.0
5.0
Fig. 6. Percent recovery (1 − 3 ) from inlet to APS and SMPS by particle size.
results clearly demonstrate the accuracy of the new inhalation system when measuring inhaled and exhaled aerosols under simulated breathing conditions. 3.4. Comparison of monodisperse deposition data to polydisperse data from the new system Paired t-tests found no signiIcant diAerence for 3 m particles when comparing the deposition of monodisperse particles with the deposition of the 3 m discrete section of a polydisperse aerosol, i.e. the 3 m bins from APS and SMPS data. Deposition values for 3 m monodisperse particles and the 3 m discrete section of a polydisperse aerosol were 6:83%±2:68 and 6:09%±1:69, respectively, for a low deposition condition. For a high deposition condition, values for 3 m monodisperse particles and the 3 m discrete section of a polydisperse aerosol were 69:24% ± 3:38 and 71:40% ± 1:73, respectively. Fig. 10 shows mean deposition values with standard error bars for both the monodisperse and the discrete section of the polydisperse aerosol at high and low deposition levels. The good agreement between the monodisperse and the discrete section of the polydisperse aerosol indicates
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1443
120
Recovery, %
100 80 60
0.3 micron 0.5 micron 1.0 micron 2 micron 3 micron 5 micron
40 20 0 0
1
3
2
4
5
Time (min)
Fig. 7. Time dependent percent recovery (1 − 2 (t)) from outlet lines, outlet valve, exhalation bag and diAusion dryer by particle size. 120
Recovery, %
100 80 60 2
y = -1.3782x - 10.804x + 101.45 2 R = 0.9978
40 20 0 0.0
1.0
2.0
3.0
4.0
5.0
Particle Diameter, µm
Fig. 8. Percent recovery (1 − 2 (t = 3 min)) by particle size from outlet lines, outlet valve, exhalation bag, and diAusion dryer with three minute exhalation bag hold.
that the new inhalation system is suitable to study the deposition of polydisperse aerosols. However, the present results are based on a well-deIned aerosol and simple, simulated breathing conditions. Our validation results may not be applied to the human lungs, and the suitability of the system for use with complex and unstable aerosols needs to be examined. 4. Conclusions A system to generate and measure polydisperse aerosols has been developed to characterize particle deposition in human lung. Data obtained from the new aerosol inhalation system, and corrected
1444
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
Percent Deposition
(a) 70 60
Photometer System Polydisperse System
50 40 30 20 10 0
Low Deposition (b)
80 70
Percent Deposition
High Deposition
60
Photometer System Polydisperse System
50 40 30 20 10 0
Low Deposition
High Deposition
Fig. 9. (a) Average percent deposition with error bars for monodisperse 1 m particles at high and low deposition levels. While diAerences between the two systems are statistically signiIcant due to the low variances, the actual diAerences were minimal. (b) Average percent deposition with error bars for monodisperse 3 m particles at high and low deposition levels. The diAerences between the two systems were not statistically signiIcant.
using the derived loss equations, compares well to data from a pre-existing photometer system capable of generating monodisperse aerosols only. Also, same size particle deposition during simulated breathing of both monodisperse and polydisperse aerosols is comparable when using the new system. The new system can be used to determine the deposition of polydisperse aerosol in the human lung directly, thus precluding the use of a monodisperse aerosol series to simulate polydisperse aerosol data. This advantage is important as it substantially reduces both study length and subject exposure. Acknowledgements The authors would like to thank the members of the Baity Laboratory at the University of North Carolina at Chapel Hill and TRC, Incorporated, Chapel Hill, for their assistance and valuable input into this project.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1445
80 70
Discrete Polydisperse Particles Monodisperse Particles
Percent Deposition
60 50 40 30 20 10 0
Low Deposition
High Deposition
Fig. 10. Average percent deposition with error bars for 3 m monodisperse and the 3 m discrete section of a polydisperse aerosol at high and low deposition levels. The diAerences between the two aerosols were not statistically signiIcant.
Jacky A. Rosati was funded under a Department of Education Fellowship for Interdisciplinary Doctoral Research in Environmental Engineering and a US EPA Training Agreement with the University of North Carolina, Department of Environmental Sciences and Engineering (CT 826513). Disclaimer Although the research described in this article has been supported by the US Environmental Protection Agency, it has not been subjected to Agency review and therefore does not necessarily re8ect the views of the Agency and no oGcial endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. References Davies, C. N., Heyder, J., & Subba Ramu, M. C. (1972). Breathing of half-micron aerosols I. Experimental. Journal of Applied Physiology, 32, 591–600. Diu, C. K., & Yu, C. P. (1983). Respiratory tract deposition of polydisperse aerosols in humans. American Industrial Hygiene Association Journal, 44, 62–65. Dockery, D. W., & Pope, C. A. III. (1994). Acute respiratory eAects of particulate air pollution. Annual Review of Public Health, 15, 107–132. Dockery, D. W., Pope, C. A. III., XU, C., Spengler, J. D., Ware, J. H., Fay, M. E., Ferris, B. G., & Speizer, F. E. (1993). An association between air pollution and mortality in six U.S. cities. New England Journal of Medicine, 329, 1753–1759. Ferron, G. A., Karg, E., & Peter, J. E. (1993). Estimation of deposition of polydisperse hygroscopic aerosols in the human respiratory tract. Journal of Aerosol Science, 24, 655–670. Heyder, J., Gebhart, J., Heigwer, G., Roth, C., & Stahlhofen, W. (1973). Experimental studies of the total deposition of aerosol particles in the human respiratory tract. Journal of Aerosol Science, 4, 191–208. James, A. C., Jarabek, A. M., Morrow, P., Schlesinger, R. B., Snipes, M. B., & Yu, C. P. (1996). Dosimetry of inhaled particle in the respiratory tract. USEPA, Air Quality Criteria Document for Particulate Matter. John, W. (1993). The characteristics of environmental and laboratory-generated aerosols. In K. Willeke, & P. A. Baron (Eds.), Aerosol measurement: Principles, techniques, and applications. New York: Van Nostrand Reinhold.
1446
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
Kim, C. S., & Hu, S. C. (1998). Regional deposition of inhaled particles in human lungs: comparison between men and women Journal of Applied Physiology, 84, 1834–1844. Kim, C. S., Hu, S. C., DeWitt, P., & Gerrity, T. R. (1996). Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. Journal of Applied Physiology, 81, 2203–2213. MacNee, W., & Donaldson, K. (1999). Particulate air pollution: Injurious and protective mechanisms in the lungs, air pollution and health. In S. T. Holgate, H. S. Koren, R. L. Maynard, & J. M. Samet (Eds.), Air pollution and health. New York: Academic Press. Utell, M. J., & Frampton, M. W. (1995). Particles and mortality: A clinical perspective. Inhalation Toxicology, 7, 645–655. Wanner, A., Brodnan, J. M, Perez, J., Henke, K. G., & Kim, C. S. (1985). Variability of airway responsiveness to histamine aerosol in normal subjects. American Review of Respiratory Disease, 131, 3–7. Wark, K., & Warner, C. F. (1981). Air pollution: Its origin and control. New York: Harper Collins. Wilson, F. J., Hiller, F. C., Wilson, J. D., & Bone, R. C. (1985). Quantitative deposition of ultraIne stable particles in the human respiratory tract. Journal of Applied Physiology, 58, 223–229.
A polydisperse aerosol inhalation system designed for human studies Jacky A. Rosatia; ∗ , James S. Brownb , Thomas M. Petersa , David Leitha , Chong S. Kimc a
Department of Environmental Sciences and Engineering, University of North Carolina, CB# 7431, 104 Rosenau Hall, Chapel Hill, NC, 27599-7431, USA b Center for Environmental Medicine and Lung Biology, Chapel Hill, NC, USA c U.S. EPA National Health and Environmental E-ects Research Laboratory, Human Studies Division, Chapel Hill, NC, USA Received 14 January 2002; received in revised form 28 May 2002; accepted 29 May 2002
Abstract A polydisperse aerosol inhalation system has been developed to measure particle deposition in the lungs of human subjects. Nebulizers are used to generate aerosols with mass median aerodynamic diameters from 0.3 to 3 m, and geometric standard deviations of 1.8–2.0. Inspired aerosol is drawn from a holding bag, passes through a sliding valve and a pneumotachograph, and enters a heated mouthpiece. Exhaled aerosol passes from the mouthpiece and pneumotachograph, through a second sliding valve and is collected in a heated sample bag. Inhalation and exhalation valves trigger automatically with change in 8ow direction through the pneumotachograph. Complete size distributions of inhaled and exhaled aerosol are measured by an aerodynamic particle sizer and a scanning mobility particle sizer. Fractional particle deposition of a test aerosol in the lung is determined by comparing inhaled and exhaled aerosol size fractions. Total deposition is determined from the sum of the fractional depositions. This new system precludes the need for monodisperse aerosol series to simulate polydisperse aerosol data, thus substantially reducing both study length and subject exposure. ? 2002 Elsevier Science Ltd. All rights reserved. Keywords: Polydisperse aerosol; Inhalation; Deposition
1. Introduction Although deposition of monodisperse aerosols in the human lung has been extensively investigated, few data are available on the deposition of polydisperse aerosols. The deposition of polydisperse ∗
Corresponding author. Tel.: +1-919-966-0632; fax: +1-919-966-6367. E-mail address: [email protected] (J.A. Rosati).
0021-8502/02/$ - see front matter ? 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 0 2 1 - 8 5 0 2 ( 0 2 ) 0 0 0 8 7 - 3
1434
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
aerosols is important because aerosols in ambient and occupational settings are polydisperse (James et al., 1996, Chap. 10) and these aerosols have been associated with adverse health eAects (Dockery et al., 1993; Dockery & Pope, 1994). Recent studies suggest airborne particulate matter, at concentration levels below present US National Ambient Air Quality Standards and United Kingdom PM-10 workplace regulations, negatively aAect human health and worker productivity (Utell & Frampton, 1995; MacNee & Donaldson, 1999, Chap. 30; Wark & Warner, 1981). Due to the lack of polydisperse data, deposition of a series of monodisperse aerosols in the human lung has been used to simulate polydisperse aerosol deposition in modeling (Diu & Yu, 1983; Ferron, Karg, & Peter, 1993). Use of this method assumes that particle interactions in the human lung from coagulation and scavenging will be negligible provided that aerosol concentrations are suGciently low (Diu & Yu, 1983). Whether this is truly the case, and whether interactive forces beyond coagulation and scavenging are present in the human lung remains a question. The present paper describes a method to directly measure the deposition of polydisperse aerosols in the human lung. While the aerosol delivery system used in this method is similar to those used previously, older systems are limited in their aerosol measurement ability. Most traditional systems determine only total deposition of monodisperse aerosols using a photometer or laser, although some have looked at total deposition of polydisperse aerosols using a laborious Ilter method, and others have analyzed only the aerosol’s ultraIne fraction (Davies, Heyder, & Subba Ramu, 1972; Heyder, Gebhart, Heigwer, Roth, & Stahlhofen, 1973; Wanner, Brodnan, Perez, Henke, & Kim, 1985; Wilson, Hiller, Wilson, & Bone, 1985). The current system can measure the complete size distribution of both an inhaled and exhaled polydisperse aerosol from 0.015 to 15:4 m. It can determine both the total deposition of an inhaled aerosol as well as the fractional deposition of multiple particle sizes within this aerosol. Use of this new method would preclude the need to use a series of monodisperse aerosols to simulate a polydisperse aerosol in modeling, would account for particle interactions, would allow inhalation studies to be conducted more rapidly, and by doing so, would substantially reduce human subject exposure during studies. 2. Methods and setup Fig. 1 is a schematic of the apparatus used, which can be broken into three components: the aerosol generation system, the inhalation system, and the aerosol measurement system. 2.1. Aerosol generation system Polydisperse aerosol is generated using a three-jet Collison nebulizer (BGI, Inc., Waltham, MA) and DeVilbiss Model 40 Glass nebulizer (Sunrise Medical, Somerset, PA). Nebulizers were chosen based on generated aerosol size. The Collison nebulizer produces wet droplets with a maximum mass median aerodynamic diameter (MMAD) of 2 m and a geometric standard deviation (GSD) of 1.8–2.0 at an air 8ow of 7:1 lpm and operating pressure of 20 psi. The DeVilbiss nebulizer produces wet droplets with a maximum MMAD of 4:2 m and a GSD of 1.8–2:0 at an air 8ow of 11 lpm and operating pressure of 10 psi (John, 1993, Chap. 5). For testing purposes, non-hygroscopic di-2-ethylhexyl sebacate was nebulized. Solutions were prepared by dissolving sebacate in ethyl
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 Mouthpiece & Pneumotach Pressure Transducer Outlet Valve
Signal Modulation & Data Acquisition
1435
Compressed Air
Inlet Valve DataRam Nebulizer
Heated Exhale Bag
Inhale Bag
Neutralizer
Three-way Valve
SMPS APS
Dilution Air In & Vacuum Air Out of Mixing Chambers
Fig. 1. Schematic of polydisperse aerosol generation and measurement system designed for human studies.
alcohol. Final particle size is dependent on the maximum wet droplet size of the nebulizer and the cube root of the solute-to-solvent concentration. The Collison nebulizer, with solute-to-solvent concentrations of 0.3% and 13%, was used to generate sebacate aerosols with MMADs of 0.3 and 1:0 m, respectively. The DeVilbiss nebulizer, with a solute-to-solvent concentration of 36%, was used to generate sebacate aerosol with a MMAD of 3:0 m. A syringe pump (Harvard Apparatus, Millis, MA) provides a constant feed of solution to the nebulizers to minimize the change in solution concentration due to solvent evaporation and thus, minimize the change in generated particle size. A three-stage dilution system is used to reduce the concentration of the aerosol to levels acceptable for a human exposure study (less than 2 mg=m3 ). Nebulized aerosol enters a 2l mixing chamber and a portion of the aerosol is removed with a vacuum system. The remainder of the aerosol is diluted with Iltered air and proceeds through two additional chambers where the process is repeated. After the Inal dilution, sampling with a Drager pump (Drager, Germany) found ethyl alcohol to be non-detectable. From the dilution process, aerosol proceeds through a Kr-85 charge neutralizer (TSI, Inc., St. Paul, MN) before entering the inhalation bag.
1436
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
2.2. Inhalation system The subject breathes through a removable, Te8on-covered brass mouthpiece while following a computer-generated breathing pattern. As a breath is drawn, a pneumatically controlled three-way slide valve opens (Hans Rudolph, Kansas City, MO) and aerosol enters the heated mouthpiece from a 25 l latex rubber bag. This bag ensures that the subject has enough aerosol to breathe at all times, even when aerosol 8ow is lower than the inhaled 8ow. On expiration, the inhalation valve closes and a second slide valve opens, directing exhaled aerosol into a second 25 l latex rubber bag that is housed in a heated plexiglass box. This exhalation bag accumulates approximately 15 –20 l of ◦ exhaled aerosol for sampling. Heating the bag and surrounding box to 38 C (body temperature) prevents condensation of water vapor, thus reducing loss of aerosol to the interior walls of the bag. Dessicant packs that line the bag serve to dry the aerosol before it passes through a diAusion dryer and into the sampling equipment. Prior to each test, the exhalation bag is 8ushed with clean air and put under a vacuum to remove residual air. Inspiratory and expiratory 8ows are measured by a Fleisch No. 1 pneumotachograph. Flow resistance through the pneumotachograph corresponds to pressure drop, which is converted to voltage by a pressure transducer (Model 239, Setra Systems, Acton, MA) and then relayed to an analog-to-digital converter (Model 2801A, Data Translation, Marlboro, MA) in a desktop computer. The 8ow data are acquired at 40 Hz and analyzed using ASYST software (ASYST Software Technologies, Rochester, NY). This software was also used to calibrate the 8ow and volume through the pneumotachograph and to open and close the slide valves. The program allows the triggering of inlet and outlet slide valves with change in 8ow direction through the pneumotachograph. When the inlet valve opens, the outlet valve closes and vice versa to avoid re-inhalation of exhaled air. The program also generates a desired breathing pattern for a subject to follow on the computer screen. This program can be modiIed to accommodate various tidal volumes (TV), 8ow rates, and breath holds. Furthermore, this software tracks the length of time from initial inhalation to APS and SMPS sampling, as well as the total volume exhaled into the bag. 2.3. Aerosol measurement system A DataRam (MIE, Inc., Billerica, MA) continuously measures the aerosol concentration at the outlet of the inhalation bag to ensure that inhaled aerosol concentration is suGciently low for human subject studies, i.e. less than 2 mg=m3 . The DataRam, a light scattering device used to determine total mass concentration of aerosols, was calibrated for each test aerosol using gravimetric Ilter samples. To determine fractional deposition, inhaled and exhaled aerosol is measured with an aerodynamic particle sizer (APS) (Model 3310, TSI, Inc., St. Paul, MN) and a scanning mobility particle sizer (SMPS) consisting of an electrostatic classiIer (Model 3071, TSI, Inc., St. Paul, MN) and a condensation particle counter (Model 3022, TSI, Inc., St. Paul, MN). The APS measures particles with a diameter ¿ 0:7 m while the SMPS is used for particles ¡ 0:7 m. The APS samples at 5 lpm, with 1 lpm of aerosol 8ow and 4 lpm of sheath air. A 60-s sample is used, and APS size limits were set to range from 0.75 to 15:399 m. The SMPS samples at 0:3 lpm through an impactor with a 0:508 mm diameter oriIce. At these operating conditions, the impactor provides a 50% cut size of 0:808 m, which eliminates larger particles that can distort the measured particle size distribution.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1437
For a given sample 8ow, size limits of the SMPS are governed by sampling time. Using 60-s upscan and 30-s downscan, the measurable SMPS size range is 14.9 –700 nm. The data from both the APS and SMPS are then merged to provide a complete size distribution. A three-way manual valve (Hans Rudolph, Kansas City, MO) is used to control the aerosol sampling location. Prior to each run, the valve is oriented to sample aerosol at the outlet of the inhalation bag (Fig. 1). After a suGcient volume of respired air is collected in the exhalation bag, the valve is switched so that exhaled aerosol is sampled directly from the middle of the heated bag. 2.4. Validation and optimization of data from the APS and SMPS The sizing accuracy of the APS and SMPS systems was validated using aerosolized monodisperse polystyrene latex (PSL) spheres (Duke ScientiIc Corp., Palo Alto, CA) from 0.2 to 5 m in diameter. PSL spheres in deionized water were nebulized using a Retec Medical Nebulizer (Retec=DeVilbiss, Somerset, PA), dried by passing through a diAusion dryer, and sampled from a small chamber by the APS and SMPS. Calibration curves were developed by comparing the APS and SMPS data to the PSL sphere sizes. The complete aerosol distribution, developed from merged APS and SMPS data, was validated using a Sierra 210 Cascade Impactor (Anderson Instruments Inc., Smyrna, GA) and an InTox Impactor (InTox, Albuquerque, NM) operated at 5 and 10 lpm, respectively. The InTox impactor was operated at a higher 8ow rate to achieve cut sizes less than 1 m. Impactor 8ows were calibrated prior to testing with a Gilibrator Primary Standard Air8ow Calibrator (Gilian Instrument Corp, Wayne, NJ). Impactors were used to validate the aerosol distribution because they directly measure mass, and are generally considered a ‘primary standard’ for measuring aerosol mass size distributions. Polydisperse aerosol was generated using a Collison nebulizer. Nebulized aerosol was routed to a mixing chamber where it was sampled by the APS, SMPS, Sierra 210, and InTox concurrently. Four sampling runs were performed to ensure precision of the measurements and merging technique. For all tests, the aerosol concentration was kept between 1 and 2 mg=m3 , the level at which subjects will be exposed. Sampling time was approximately 180 min to collect suGcient mass on the impactor substrates and Ilter for gravimetric analysis. APS and SMPS samples were taken consecutively at 5-min intervals, and runs were averaged by bin to provide a single time-averaged size distribution that could be directly compared to the impactor measurements. The data merging method was optimized by trial and error to maximize agreement between the data sets. 2.5. System removal e;ciencies Particle loss, , was determined for each part of the inhalation system. Here, varies with particle diameter and represents the fraction of an incoming aerosol that collects in the part of the system in question. DiAerent sized monodisperse test aerosols were run through each part of the inhalation system. Concentration was measured using two calibrated DataRams—one upstream and one downstream of the system part evaluated. Removal eGciency could then be determined from =1−Cdown =Cup , where Cdown represents downstream concentration and Cup represents that upstream. Fig. 2 shows each sampling location in the inhalation system.
1438
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 Mouthpiece & Pneumotach
Sampling Position #2 (conc #2)
Exhaled Aerosol = CB
Sampling Position #1 (conc #1) Inlet Aerosol = CA
Heated Exhalation Bag
Inhalation Bag
Definition of Losses or Efficiencies: η 1= 1-(conc #2/conc #1) η 2= 1-(conc #3/conc #2) η 3= 1-(conc #3/conc #1)
Aerosol
Three-way Valve Sampling Position #3 (conc #3) Classifier & CPC APS
Fig. 2. DeInition of system removal eGciencies, 1 , 2 and 3 , and sampling locations in the inhalation system. CA = concentration of inlet aerosol into the system and CB = concentration of aerosol exhaled at mouthpiece, both as measured by the APS and SMPS. Sampling locations (denoted by crosses) represent placement of DataRams during loss testing.
Particle deposition eGciency in the lung can then be calculated by Eq. (1) Deposition eGciency = 1 − =1−
Exhaled particle concentration Inhaled particle concentration CB (1 − 3 ) ; CA (1 − 1 )(1 − 2 (t))
(1)
where CA is the concentration of inlet aerosol into the system as measured by the APS and SMPS, CB is the concentration of aerosol exhaled at mouthpiece as measured by the APS and SMPS, 1 is the loss for inlet line, inlet valve, and mouthpiece, 2 (t) is the time-dependent loss for outlet lines, outlet valve, exhalation bag and diAusion dryer, 3 is the loss for sampling line from inlet to APS and SMPS, and, 1 − is the recovery, or particles that are not deposited in the sample lines. As aerosols are collected in the exhalation bag for a number of breaths, preliminary studies indicate that the aerosol may remain in the bag for up to 5 min before sampling with the APS and SMPS. 2 (t) losses were determined for 0 –5 min bag holding times allowing the appropriate correction to be applied based on residence time in the bag prior to APS and SMPS sampling.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1439
2.6. Preliminary testing Two types of preliminary testing were performed. First, the new polydisperse aerosol inhalation system was tested against an existing, photomoter-based system (Kim & Hu, 1998; Kim, Hu, DeWitt, & Gerrity, 1996) using monodisperse aerosols. Second, the new inhalation system was tested with polydisperse aerosols to compare the deposition of monodisperse particles to the deposition of discrete sections of the polydisperse aerosol. The new inhalation system was tested against the photometer system using a Harvard Pump (Harvard Apparatus, Millis, MA) to simulate breathing. Monodisperse sebacate particles (1 and 3 m) were produced by a monodisperse aerosol generator (MAGE) (Lavoro E Ambiente, Bologna, Italy). Aerosol concentration was approximately 3 mg=m3 for each system. The concentration was high enough to provide stable signals for the photometer system, and low enough to minimize coincidence error in the APS and SMPS system. Stainless-steel screens were placed in a Ilter holder prior to the Harvard Pump. Screen mesh size was varied to achieve the desired level of deposition for each particle size tested. The pump was set to ‘breathe’ with a tidal volume of 0:75 l and a 8ow rate of 250 ml=s. Aerosol was ‘inhaled’ and ‘exhaled’ by the pump on each system, and deposition for each aerosol size was determined. Nine or more runs were performed for each particle size at both a high and low deposition levels. Deposition for the two systems was then compared for each particle size using a paired t-test. To compare monodisperse particle deposition with discrete sections of polydisperse aerosol deposition, a polydisperse aerosol with an MMAD of 3 m and GSD of 2.0 was generated, and the Harvard Pump was set up with the same parameters as the above experiment. Again, nine runs were performed at both a high and low deposition levels. Deposition data for the monodisperse particles were then compared to the deposition of discrete sections of the polydisperse aerosol, i.e. 3 m bin from APS and SMPS data, using a paired t-test. 3. Results and discussion 3.1. Validation of data from the APS and SMPS The sizing accuracy of the APS and SMPS system was validated using aerosolized polystyrene latex (PSL) spheres. Several sphere diameters were used, and data for the actual sizes as determined by the manufacturer are plotted versus the measured size in Fig. 3. Error bars that represent one standard deviation are not visible in the Igure because the error was so small (less than 2%). Comparisons of the size distribution of a polydisperse aerosol measured simultaneously with the APS and SMPS system and two diAerent cascade impactors are presented in Figs. 4a and b. The data were compared as mass concentration frequencies to account for diAerences in sample mass between the three instruments in Fig. 4a. Presentation of the data in this form shows reasonably good agreement between the instruments, with some discrepancies between the impactor and APS and SMPS data. The SMPS overestimated aerosol concentration between 0.3 and 0:6 m when compared to the cascade impactors, and the APS underestimated aerosol concentration between 0.7 and 1:9 m when compared to the impactors. Such discrepancies between the SMPS, APS and cascade impactors were expected because each instrument uses a diAerent measurement technique
1440
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 6.0
Measured Average PSL DP, µm
1:1 Line 5.0
SMPS APS
4.0
3.0
2.0
1.0
0.0 0.0
1.0
2.0
3.0
4.0
5.0
6.0
Actual PSL Dp, µm
Fig. 3. Diameter of PSL spheres measured with the APS and SMPS system compared to size reported by the manufacturer.
and has diAerent measurement error. In addition, error is introduced during the conversion from number count into mass of particles. As respiratory deposition is determined by the ratio of exhaled to inhaled aerosol for each particle size, these discrepancies should pose no signiIcant problems. The similarity in the cumulative mass size distributions (MMAD = 1:12 ± 0:08 and GSD = 1:98 ± 0:05) presented in Fig. 4b suggests that the discrepancies have a minimal eAect on size distribution. 3.2. System removal e;ciencies System losses () were determined for several diAerent size particles. Figs. 5 and 6 show percent recovery, 1 − 1 and 1 − 3 , as a function of particle size for sebacate oil aerosol. Recovery data were It to a curve and the curve’s equation (given on the Igure) was used for raw APS and SMPS data correction. All curves It had an R2 value of 0.96 or greater. Fig. 7 shows changes in recovery, 1 − 2 (t), for each particle size as a function of residence time in the exhalation bag. Fig. 8 shows recovery as a function of aerosol size for an exhalation bag=line hold time of 3 min. Again, recovery data were It to a curve, and the curve’s equation was used to correct raw APS and SMPS data. The R2 value of each curve was 0.99 or greater. 3.3. Comparison of new system to photometer-based system The loss correction equations and the new inhalation system were validated against a pre-existing photometer system. Deposition values for 3 m particles on the new system and the photometer-based system were 7:86% ± 5:84 and 7:74% ± 0:37, respectively, for a low deposition condition. For a high deposition condition, values for 3 m particles on the new system and the photometer-based system were 69:17% ± 2:99 and 72:67% ± 0:52, respectively. Paired t-tests found no signiIcant diAerence in the corrected deposition data acquired by the new system and the photometer-based system for 3 m particles. Deposition values for 1 m particles on the new system and on the photometer-based system were 22.0% ± 0:39 and 19:5% ± 0:13, respectively, for a low deposition condition. For a
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1441
1.60 Sierra Impactor
Mass Concentration Frequency
1.40
Intox Impactor
1.20
APS & SMPS Merged Data
1.00 0.80 0.60 0.40 0.20 0.00 0.10
1.00 Particle Diameter, µm
(a)
10.00
10
Particle Size, µm
Intox Sierra APS & SMPS
1
(b)
0.9999
0.999
0.99
0.9
0.95
0.2 0.3 0.4 0.5 0.6 0.7 0.8
0.1
0.05
0.01
0.001
0.0001
0.1
Cumulative Mass Probability Less Than Indicated Particle Size
Fig. 4. (a) Mass frequency plot of merged APS and SMPS sampling data compared to sampling data for two types of cascade impactor. (b) Cumulative distribution plot of merged APS and SMPS sampling data, as well as sampling data for two types of cascade impactor. MMAD and GSD comparable for all sampling instruments.
high deposition condition, values for 1 m particles on the new system and the photometer-based system were 63:20% ± 0:97 and 62:14% ± 0:21, respectively. Although t-tests yielded a signiIcant diAerence in the deposition data acquired by the two systems for 1 m particles, this diAerence was less than 1% and was deemed unimportant. Figs. 9a and b show mean values with standard error bars for monodisperse 1 and 3 m particles, respectively, at high and low deposition levels. The
1442
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446 120
Recovery, %
100 80 2
y = -0.6114x - 2.1986x + 99.833 2 R = 0.963
60 40 20 0 0.0
1.0
2.0
3.0
4.0
5.0
Particle Diameter, µm
Fig. 5. Percent recovery (1 − 1 ) from inlet line, inlet valve, and mouthpiece by particle size. 120
Recovery, %
100 80
2
y = -2.895x + 6.8131x + 97.416 2 R = 0.9979
60 40 20 0 0.0
1.0
2.0 3.0 Particle Diameter, µm
4.0
5.0
Fig. 6. Percent recovery (1 − 3 ) from inlet to APS and SMPS by particle size.
results clearly demonstrate the accuracy of the new inhalation system when measuring inhaled and exhaled aerosols under simulated breathing conditions. 3.4. Comparison of monodisperse deposition data to polydisperse data from the new system Paired t-tests found no signiIcant diAerence for 3 m particles when comparing the deposition of monodisperse particles with the deposition of the 3 m discrete section of a polydisperse aerosol, i.e. the 3 m bins from APS and SMPS data. Deposition values for 3 m monodisperse particles and the 3 m discrete section of a polydisperse aerosol were 6:83%±2:68 and 6:09%±1:69, respectively, for a low deposition condition. For a high deposition condition, values for 3 m monodisperse particles and the 3 m discrete section of a polydisperse aerosol were 69:24% ± 3:38 and 71:40% ± 1:73, respectively. Fig. 10 shows mean deposition values with standard error bars for both the monodisperse and the discrete section of the polydisperse aerosol at high and low deposition levels. The good agreement between the monodisperse and the discrete section of the polydisperse aerosol indicates
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1443
120
Recovery, %
100 80 60
0.3 micron 0.5 micron 1.0 micron 2 micron 3 micron 5 micron
40 20 0 0
1
3
2
4
5
Time (min)
Fig. 7. Time dependent percent recovery (1 − 2 (t)) from outlet lines, outlet valve, exhalation bag and diAusion dryer by particle size. 120
Recovery, %
100 80 60 2
y = -1.3782x - 10.804x + 101.45 2 R = 0.9978
40 20 0 0.0
1.0
2.0
3.0
4.0
5.0
Particle Diameter, µm
Fig. 8. Percent recovery (1 − 2 (t = 3 min)) by particle size from outlet lines, outlet valve, exhalation bag, and diAusion dryer with three minute exhalation bag hold.
that the new inhalation system is suitable to study the deposition of polydisperse aerosols. However, the present results are based on a well-deIned aerosol and simple, simulated breathing conditions. Our validation results may not be applied to the human lungs, and the suitability of the system for use with complex and unstable aerosols needs to be examined. 4. Conclusions A system to generate and measure polydisperse aerosols has been developed to characterize particle deposition in human lung. Data obtained from the new aerosol inhalation system, and corrected
1444
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
Percent Deposition
(a) 70 60
Photometer System Polydisperse System
50 40 30 20 10 0
Low Deposition (b)
80 70
Percent Deposition
High Deposition
60
Photometer System Polydisperse System
50 40 30 20 10 0
Low Deposition
High Deposition
Fig. 9. (a) Average percent deposition with error bars for monodisperse 1 m particles at high and low deposition levels. While diAerences between the two systems are statistically signiIcant due to the low variances, the actual diAerences were minimal. (b) Average percent deposition with error bars for monodisperse 3 m particles at high and low deposition levels. The diAerences between the two systems were not statistically signiIcant.
using the derived loss equations, compares well to data from a pre-existing photometer system capable of generating monodisperse aerosols only. Also, same size particle deposition during simulated breathing of both monodisperse and polydisperse aerosols is comparable when using the new system. The new system can be used to determine the deposition of polydisperse aerosol in the human lung directly, thus precluding the use of a monodisperse aerosol series to simulate polydisperse aerosol data. This advantage is important as it substantially reduces both study length and subject exposure. Acknowledgements The authors would like to thank the members of the Baity Laboratory at the University of North Carolina at Chapel Hill and TRC, Incorporated, Chapel Hill, for their assistance and valuable input into this project.
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
1445
80 70
Discrete Polydisperse Particles Monodisperse Particles
Percent Deposition
60 50 40 30 20 10 0
Low Deposition
High Deposition
Fig. 10. Average percent deposition with error bars for 3 m monodisperse and the 3 m discrete section of a polydisperse aerosol at high and low deposition levels. The diAerences between the two aerosols were not statistically signiIcant.
Jacky A. Rosati was funded under a Department of Education Fellowship for Interdisciplinary Doctoral Research in Environmental Engineering and a US EPA Training Agreement with the University of North Carolina, Department of Environmental Sciences and Engineering (CT 826513). Disclaimer Although the research described in this article has been supported by the US Environmental Protection Agency, it has not been subjected to Agency review and therefore does not necessarily re8ect the views of the Agency and no oGcial endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. References Davies, C. N., Heyder, J., & Subba Ramu, M. C. (1972). Breathing of half-micron aerosols I. Experimental. Journal of Applied Physiology, 32, 591–600. Diu, C. K., & Yu, C. P. (1983). Respiratory tract deposition of polydisperse aerosols in humans. American Industrial Hygiene Association Journal, 44, 62–65. Dockery, D. W., & Pope, C. A. III. (1994). Acute respiratory eAects of particulate air pollution. Annual Review of Public Health, 15, 107–132. Dockery, D. W., Pope, C. A. III., XU, C., Spengler, J. D., Ware, J. H., Fay, M. E., Ferris, B. G., & Speizer, F. E. (1993). An association between air pollution and mortality in six U.S. cities. New England Journal of Medicine, 329, 1753–1759. Ferron, G. A., Karg, E., & Peter, J. E. (1993). Estimation of deposition of polydisperse hygroscopic aerosols in the human respiratory tract. Journal of Aerosol Science, 24, 655–670. Heyder, J., Gebhart, J., Heigwer, G., Roth, C., & Stahlhofen, W. (1973). Experimental studies of the total deposition of aerosol particles in the human respiratory tract. Journal of Aerosol Science, 4, 191–208. James, A. C., Jarabek, A. M., Morrow, P., Schlesinger, R. B., Snipes, M. B., & Yu, C. P. (1996). Dosimetry of inhaled particle in the respiratory tract. USEPA, Air Quality Criteria Document for Particulate Matter. John, W. (1993). The characteristics of environmental and laboratory-generated aerosols. In K. Willeke, & P. A. Baron (Eds.), Aerosol measurement: Principles, techniques, and applications. New York: Van Nostrand Reinhold.
1446
J.A. Rosati et al. / Aerosol Science 33 (2002) 1433 – 1446
Kim, C. S., & Hu, S. C. (1998). Regional deposition of inhaled particles in human lungs: comparison between men and women Journal of Applied Physiology, 84, 1834–1844. Kim, C. S., Hu, S. C., DeWitt, P., & Gerrity, T. R. (1996). Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. Journal of Applied Physiology, 81, 2203–2213. MacNee, W., & Donaldson, K. (1999). Particulate air pollution: Injurious and protective mechanisms in the lungs, air pollution and health. In S. T. Holgate, H. S. Koren, R. L. Maynard, & J. M. Samet (Eds.), Air pollution and health. New York: Academic Press. Utell, M. J., & Frampton, M. W. (1995). Particles and mortality: A clinical perspective. Inhalation Toxicology, 7, 645–655. Wanner, A., Brodnan, J. M, Perez, J., Henke, K. G., & Kim, C. S. (1985). Variability of airway responsiveness to histamine aerosol in normal subjects. American Review of Respiratory Disease, 131, 3–7. Wark, K., & Warner, C. F. (1981). Air pollution: Its origin and control. New York: Harper Collins. Wilson, F. J., Hiller, F. C., Wilson, J. D., & Bone, R. C. (1985). Quantitative deposition of ultraIne stable particles in the human respiratory tract. Journal of Applied Physiology, 58, 223–229.