J. Aerosol Sci., Vol. 23, Suppl. 1, pp. $477-$481, 1992 Printed in Great Britain.
0021-8502/92 $5.00 +0.00 Pergamon Press Ltd
The Recovery of lpm Aerosol Particles from Large Human Airways Gerhard Scheuch and Willi Stahlhofen GSF Forschungszentrum fiir Umwelt und Gesundheit Paul-Ehflich-Strasse 20, D-6000 FRANKFURT, GERMANY -
ABSTRACT Aerosol particles with aerodynamic diameters (dae) of about 1.1/,~m were inspired into human conducting airways by the bolus inhalation technique. Inhaling small volumes of aerosols ("20 cm 3 - boluses") at the very end of a clean air inhalation these particles should only reach conducting human airways. Particle recoveries (RC) in the exhaled air after various periods of breath holding (tb) were measured in front of the mouth with an aerosol laser photometer. Assuming that losses of the inhaled particles were caused by sedimentation during breath holding periods, the slope of the recovery function (RC(tb)) is a measure of the airway dimensions where the particles were located at end inhalation. This function can be estimated theoretically. By comparing bolus recovery data to model calculations, assuming different aerosol distributions in airway models, and both still and stirred settling, it could be shown that aerosol boluses inhaled to lung depths < 40 cm 3 do not reach alveolar airspaces during inhalation. KEYWORDS Aerosol Inhalation, Bolus Technique, Recovery, Particle Deposition, Human Lungs, Tracheobronchial Deposition, Deposition in Conducting Airways, Model Calculations EXPERIMENTS Material Aerosol particles were produced by condensation of di-2-ethyl-hexyi sebacate vapour on sodium chloride nuclei in a commercially available monodisperse aerosol generator (MAGE, Lavoro E Ambiente, Bologna). The generated particles were monodisperse (Og = 1.07 - 1.11) and hydrophobic. Aerosol Administration Boluses of the generated aerosol were inhaled using an inhalation device described in (Seheueh et al., 1989). Particle number concentration (c) measured with a laser photometer was recorded as a function of the respired volume using a PDPll-73 Computer (DEC, Galway, Ireland). Inspired and expired volumes (Vi. and Vex) were computed by integrating the respired flowrates (Q) measured with a Fleiseh pneumotachometer. With a magneto-pneumatic valve system operated with a personal computer small predetermined aerosol volumes were injected into the particle-free tidal air. Inhalation Protocol The inhalation manoeuvre was previously described in detail in (Scheuch and Stahlhofen, 1992). The subject staged a one litre inhalation of clean air with a constant flowrate of Q = $477
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G. SCHEUCHand W. STAHLHOFEN
250 cma/s and observed his respired flowrate at the screen of an oscilloscope. During this inhalation an aerosol bolus was injected, when the subject had inspired a preselected air volume. At the end of the inspiration all valves were closed, so that the subject could neither inspire nor expire. After a preselected period of breath holding (tb) the expiration valve was opened and the subject exhaled at the same flowrate to his residual lung volume. All experiments reported in this paper were conducted in one healthy male subject. The functional residual capacity (FRC) of this subject was 4000 cm 3. To characterize volumetric penetration of the bolus into the lungs, the following two quantities have been proved useful (Stahlhofen et al., 1987) : 1) The volumetric lung depth (VD. This is a measure of the volumetric penetration of an aerosol bolus into the respiratory tract, defined by V L = Via(max) - V, [ 1] where Via(max) is the entire inspired volume ( =1000 cm3), and V is the volume corresponding to the mean of the inspired bolus distribution.
2) The volumetricfront depth (VF) represents the maximum particle penetration into the lungs and depends on the volumetric bolus width. The particle recovery (RC) of given aerosol bolus is defined as RC = N ~ / N i n , where Nex and Nin are the total number of expired and inspired particles, respectively. THEORETICAL CALCULATIONS The calculations employs the following models: an anatomical geometric model of the airway dimensions; - a model for particle losses during periods of breath holding. a distribution of the inhaled aerosol in the airways The Anatomical Model Weibel's symmetrical model A (WA) (Weibel, 1963) was used for these calculations. The model was isometrically adapted to a lung volume of 4000 cm 3 (Yu and Diu, 1982), since all experiments were carried out at this value. The conducting airways volume (VcA) was evaluated to be VCA = 147 cm 3. The trachea was supposed to be a tube with a length of 12 cm. The oropharynx had been supposed as a tube of 1.7 cm diameter and a length of 7.5 era. The mouth cavity was filled up with a special mouth piece possessing the inner diameter 1.2 cm and the length 10 cm. The experiments were performed for a subject sitting in a posture where the angle of the trachea was about 75 o and the angle of the main bronchi 5 5o. All other airways had been assumed to be randomly oriented. The Deposition Models Deposition (DE) of particles in the airways was assumed to occur by sedimentation. Particle recovery during breath holding periods (RCb) were calculated under two assumptions: i) For particle losses by settling in a quiescent air (still settling) Heyder (1975) gave an equation for the particle recovery RCb*(still). RCb*(Still) = 2/¢r [arccos (To cos6) - T¢3 cos6 (1 - To2cOs2B) 1/2]
[2]
with TG = vs/tb (Vs = settling velocity of the particles). ii) The equation for particle deposition in stirred air (stirred settling) the equation RCb*(stirr) = exp {- (4/~r) To cos8 } had been used (Gebhart et al., 1981).
[3]
Recovery of 1/~m aerosol particles from human airways
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For randomly oriented tubes the probability density of finding a tube oriented at angle 6 to the horizontal is cosR. Hence, for a system of identical tubes the recovery is given by Heyder (1975): RCb = 2/rr 0
RC,o* cord] dfl
[41
The total recovery of a single airway of generation number oe after inhalation, breath holding and exhalation was calculated (RC~(tb)). Distribution of Aerosol in the Airways Figure 1 shows different aerosol distributions assumed to be located in the anatomical model at the end of a bolus inhalation. The lung depth (Vt.) of the inspired bolus was Vt. = 35 cm 3 and VF = 40 cm 3. 'V-Inhalat' and 'V-Exhalat' represent distributions of or, measured with the laser photometer in front of the mouth during inhalation and exhalation, respectively. Assuming a parabolic flow profile during inhalation, the concentration distribution in the airways at end inhalation is represented by 'V-Laminar'. Model Calculations A Fortran program was written to calculate the particle recovery (RC,,) of every airway generation (oe), for a given particle size and settling mechanism (still or stirred). For every airway generation with the volume V,, an apparent aerosol number concentration e~ was drawn from a bolus shape of Fig. 1. The total recovery of the bolus (RC) for a given period of breath holding (tb) was then calculated by superposition: {(c,~ • V,~) • RC,~} RC =
[5]
The summation was carried out over all airway generations. The particle recoveries R C were calculated for various aerosol concentration distributionsin the airways.
RESULTS In Fig. 2 the particle recovery is plotted as function of tb, comparing the theoretically obtained recovery results with the experimental data. As can be seen the theoretical calculation with the aerosol concentration distribution 'V-Laminar' fits the measured data pretty good. Theoretical results obtained with the distribution 'V-Exhalat' resulted in a too steep recovery function, indicating that too many particles were assumed to be located in small airways. DISCUSSION In a previous paper (Scheuch and Stahlhofen, 1991) it had been demonstrated that cardiogenic mixing has a significant influence on bolus dispersion and on particle recovery of 1/~m aerosol particles at volumetric lung depths between VL = 50 - 140 cm 3 (VF = 59 - 148 cm3). This was confirmed by measurements with aerosol boluses using different particle sizes (Scheuch and Stahlhofen, 1992). With increased heart rate aerosol particles are dispersed into smaller airways during breath holding. Particles with dae > 2/~m (vs > 130 /.~m/s) were less succeptible by eardiogenic mixing. In this study particles with dae = 1.1/zm (Vs = 40/zm/s) were used for the investigation. These particles can be effected by cardiogenic mixing. Scheuch and Stahlhofen (1991) showed that the effect of eardiogenie mixing was not effective for boluses inhaled into very shallow lung depths (VL < 40 e m 3) which are used in this study. It could be shown earlier, that the method of aerosol derived lung morphometry enables the evaluation of peripheral air space diameters (Blanchard et al., 1991). Scheuch and Stahlhofen (1991) found that cardiogenic mixing didn't affect these measurements using the bolus recovery technique in volumetric lung depths VL > 250 cm 3. Aerosol derived effective airway diameters (EAD) values in peripheral lung structures were found to be between 0.33 and 0.41 mm (Blanchard et al., 1991).
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Fig. 2: Particle Recovery after Bolus Inhalations as Function of the Period of Breath Holding Comparison between Results of Theoretical Estimations and Measurements
Recovery of 1 #m aerosol particles from human airways
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No morphometrical lung model reported in the literature, employed the diameters of terminal bronchioli or alveoli larger than 0.6 mm. For the investigated subject EAD in a volumetric lung depth of 600 cm 3 was found to be 0.34 _ 0.05 mm. From all our calculations we found that in no case a penetration of more than 3% of the aerosol particles into lung structures with DR < 1 mm could fit the measured recovery values. Calculation of the deposited fraction after tb = 10 -20 S showed that not more than 15% of the particles could reach airspaces of the above dimensions. CONCLUSIONS By comparing bolus recovery data to model calculations, assuming different aerosol distributions in the airways, and both still and stirred settling, it could be shown that aerosol boluses inhaled to volumetric lung depths < 40 cm 3 reach conducting airways during inhalation, exclusively. Less than 3% of particles from these boluses could penetrate to airspaces with diameters DR < 1 mm during inhalation. To avoid a deeper penetration of the inhaled aerosol by cardiogenic mixing during periods of breath holding, the particles should have a sufficient large settling velocity (Vs > 100/xm/sXSeheuch and Stahlhofen, 1992). ACKNOWLEDGEMENT This study was partially supported by the CEC under Contract B16-0347-Item 2. REFERENCES Blanchard, J.D., J. Heyder, C.R. O'Donnel and J.D. Brain (1991). Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes. J. Appl. Physiol. 71, 1216-1224. Gebhart, J., J. Heyder and W. Stahlhofen (1985). Use of aerosols to estimate pulmonary airspace dimensions. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51, 465-476. Heyder, J. (1975). Gravitational deposition of aerosol particles within a system of randomly oriented tubes. J. AerosolSci. 6, 133-137. Scheuch, G. and W. Stahlhofen (1991). The effect of heart rate on aerosol recovery and dispersion in human conducting airways after periods of breathholding. Exp. Lung Res. 17, 763-787. Scheuch, G. and W. Stahlhofen (1992). Deposition and Dispersion of Aerosols in the Airways of the Human Respiratory Tract: The Effect of Particle Size. Exp. Lung Res. 18, 343-358. Scheuch, G., J. Gebhart, G. Heigwer, and W. Stahlhofen (1989). A New Device for Human Inhalation Studies with small Aerosol Boluses. J. Aerosol Sci. 20, 1293-1296. Stahlhofen, W., J. Gebhart, G. Rudolf and G. Scheuch. (1987). Retention of radioactively labelled Fe203-partieles in the human lungs. In: Deposition and Clearance of Aerosols in the Human Respiratory Tract (W. Hoffmann, Ed.) Facultas Universit/itsverlag, Wien, pp. 123-128. Weibel, E.R. (1963). Morphometry of the Human Lung. Springer, Berlin. Yu, C.P. and C.K. Diu (1982). A comparative study of aerosol deposition in different lung models. Am. Ind. Hyg. Assoc. J. 43, 54-65.