Investigation into the dust deposition pattern in the respiratory tract. Final report on CEC Contract 6244-00/8/101

The deposition and short-term clearance characteristics of monodisperse aerosol particles (size range 4.5 – 13?m diameter) in the human respiratory tract have been investigated in eighteen human volunteer subjects.The primary aim of the study has been to define accurately the upper size limit of dust which is able to penetrate below the larynx and to deposit subsequently in the dead space airways. It is this size fraction of dust which may be important in the aetiology of chronic bronchitis. The experimental problems of obtaining an accurate sample of the inhaled aerosol and of controlling the physiological conditions of aerosol administration have been given particular emphasis, in order to improve on the suitability and accuracy of existing experimental techniques. A new type of apparatus has been constructed which accurately samples-the aerosol to be inhaled by a subject and at the same time ensures a rigorous control of the physiological conditions of aerosol administration.The sampling part of the device employs a simple mechanical servornechanism which consists in essence of two spirometers in mutual balance. The most important advantages of the new method are: 1. its proven accuracy even at the largest particle size employed (13 μm diameter); 2. the future possibility of studying result; 3. its cost effectiveness in terms of high accuracy at low cost compared with, for example, that of aerosol sampling techniques based on optical scatter.The experimental and historical background to the present work is discussed in order to emphasise the areas in which previous research might be open to misinterpretation and to illustrate gaps in the knowledge of aerosol behaviour in the human respiratory tract.The regional distribution of the inhaled particles within the respiratory tract has been estimated using an indirect technique, the accuracy of which depends, in part, on certain widely accepted assumptions. The method is based on the monitoring of the clearance of inhaled radioactive particles over a period of about one day. By assuming that the material cleared within this period represents only those particles which initially deposited on the ciliated dead space airways, the relative proportions of respiratory zone and dead space aerosol deposition may be estimated. A profile scanning techniquefor distinguishing between adjacent and overlapping anatomical regions has been employed (HOLMA, 1967), which is considered to be a more suitable method for this purpose than, the fixed radiation detectoi- systems employed elsewhere.The total deposition results of the present work are generally lower than those of other workers, with one exception, in a limited region of comparison, rising only slowly from a mean value of about 80% of the inhaled aerosol at 4.5μm particle diameter to about 88% at 13μm percentages being expressed in relation to the inhaled aerosol and averaged over three subjects at each particle size. Mouthwash recovery ranged from below 1% to just over 9% in the same particle size range. These figures are also lower than those reported by other workers and it is suggested that mouthpiece design and dimensions may be the most important causative factors. Aerosol losses in the laryngeal/ pharyngeal region have been carefully measured and exhibit the largest scatter of observations of any anatomical region studied, suggesting an important role for the glottal opening. The mean values at each size ranged from 9% to 42% which is lower than those reported by LIPPMANN and ALBERT (1969), whose results exhibited considerably greater scatter. Considering the rapidly increasing trend in these losses with increasing particle size it seems unlikely that particles more than several microns greater than the largest particle size employed in the present work (13m diameter) are able to penetrate below the larynx in significant amounts.Estimated percentage aerosol deposition on the dead space airways maintains a fairly constant level throughout most of the particle size range studied, rising from about 24% at 4.5m to about 36% at 6.7m and remaining at about this level up to and including 13 IM particle diameter. The estimated levels of one-day retention are higher than those of LIPPMANN and ALBERT (1969) but agree well with the one published result of STAHLHOFFEN et al. (1979)- Good agreement has also been obtainedwith the fractional retention values reported by FOORD et al. (1978) in a limited region of particle size overlap. The present results for respirable dust are about 45% retention (relative to inhaled aerosol) at ~24 hours and 4.5m particle diameter, declining steadily to about 8 1/2 at 10.4m and about 64% at 13m particle diameter. However, while these results would appear to indicate that the larger particles are able to penetrate to the respiratory zone of the lungs far more effectively than had hitherto been considered possible by most investigators, the rapid decline in the independently obtained laryngeal/trscheal clearance curves does not support this finding. Moreover, an analysis of the present data using a simple filter model of the respiratory tract demonstrates that the regional aerosol deposition results are wholly inconsistent with the expected behaviour of airborne particles in the respiratory zone. It is therefore concluded.that the measured levels of one- day retention at large particle sizes are being caused by an incomplete clearance of particles which initially deposited on the dead space airways.The ramifications of the above conclusion with respect to existing respirable dust: sampling curves are discussed and it is recommended that the results of the present work should be regarded only as an upper deposition limit, in the case of respirnblc dust, and a lower deposition limit in the case of that dust fraction which deposits on the dead space airways.An interesting secondary phenomenon has also been observed, the clearance curves exhibit distinct non-random fluctuations. By means of fixed and double radiation detectors placed, oer the laryngeal and tracheal region of the throat, it has been established that the fluctuations are not merely an artefact of the primary measuring; detector and have their origin from somewhere below the trachea, not solely in the larynx itself. The possible biological and physical factors thot may be implicated in the causation, of the clearance pulses are discussed. “”