Inhaled Particles and Vapours. Proceedings of an International Symposium Organized by the British Occupational Hygiene Society, Cambridge, 28 September–1 October 1965

632 Pages·1967·29.488 MB·English

by  C. N. Davies (Eds.)

INHALED PARTICLES
AND
VAPOURS
II
Proceedings of an International Symposium
organized by the British Occupational Hygiene Society,
Cambridge, 28 September — 1 October 1965
Edited by
C. N. DAVIES
SYMPOSIUM PUBLICATIONS DIVISION
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Copyright © 1967
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First edition 1967
Library of Congress Catalog Card No. 61-10786
(2680/67)
ORGANIZING COMMITTEE
Chairman: Mr. W: H. WALTON, Pneumoconiosis Field Research Unit, National
Coal Board.
Dr. J. M. BARNES, Director, Toxicology Research Unit, Medical Research
Council.
Dr. R. C. CURRAN, Professor of Pathology, St. Thomas's Hospital Medi­
cal School, London.
Editor: Dr. C. N. DAVIES, London School of Hygiene and Tropical Medicine.
Honorary Editor of Transactions, British Occupational Hygiene So­
ciety.
Dr. J. C. GILSON, Director, Pneumoconiosis Research Unit, Medical
Research Council.
Finance: Dr. J. G. JONES, Richard Thomas and Baldwin Limited, Ebbw Vale.
Honorary Treasurer, British Occupational Hygiene Society.
Publicity: Dr. J. S. MCLINTOCK, Medical Service, National Coal Board.
Honorary Publicity Officer, British Occupational Hygiene Society,
Dr. G. NAGELSCHMIDT, Ministry of Technology.
President, British Occupational Hygiene Society.
Secretary: Mr. R. J. SHERWOOD, Standard Oil Co. (New Jersey), London.
Honorary Business Secretary, British Occupational Hygiene Society.
Mr. S. SMITH, H.M. Factory Inspectorate.
PREFACE
FIVE years, in the advance of science, is not a period within which more than an
occasional new development can be expected. It is therefore not surprising, in the
restricted field of this volume, that the progress recorded derives intimately from the
activities covered by the first volume which was published in 1961. A change of
emphasis will be found, a rejection of some techniques, an elaboration of others, but
the main lines of research are very similar to those described at the Oxford Sympo­
sium of the British Occupational Hygiene Society in the spring of 1960. As a result,
some of the papers which were published in the earlier volume can profitably be
referred to by readers of the second.
Whereas I could write that the original symposium assembled ideas in a way not
previously attempted, it is now necessary to admit to following a prevailing fashion.
Why vapours have become so démodé as to sink in popular appeal from 13 per cent
to 2 per cent, in the present volume 1 do not understand.' That there is less of a
challenge to experimental skill, in working with a single phase, can be admitted but
it is also true that experience gained in handling vapours, both in the design of
experimental apparatus and in the interpretation of experimental results, is a useful
introduction to analogous work with particles; nor is the behaviour of inhaled
vapours devoid of subtlety.
For example, Morgan and his colleagues, in this volume, think that little or no ab­
sorption of methyl iodide occurs in the tidal airways of the lung; Teisinger (Ind. M ed.
Surg. 34,580,1965), on the other hand, working with mercury vapour which has much
the same diffusivity as methyl iodide, believes his own results show that absorption
takes place entirely upon the mucus coating of the bronchial epithelium. The retention
of the two vapours is identical, being about 75 per cent with normal breathing.
It is clear from the diifusivity, about 0*08 cm2/sec, that if every molecule of the very
dilute vapour inhaled which struck the mucus surfaces of the airway walls were to
be fixed, then all the vapour drawn in during a breath would be removed completely
by the time the inhaled air had passed beyond the segmental bronchi. Since, in fact,
about a quarter of the inhaled vapour is breathed out again, it is evident that a sub­
stantial fraction of the collisions of atoms of mercury or molecules of methyl iodide
with the walls of the airways must be followed by reflection or evaporation.
The interesting thing is that the large differences in chemical behaviour of the re-
xi
XU Preface
spective vapours should lead to claims for quite different patterns of regional deposi­
tion which are not detectable as differences in the net absorption. This thought will
elicit a sympathetic resonance in the mind of the student of particles. The view of the
writer is that it may be unwise to commit oneself too definitely on the routes through
the body which are followed by the characteristic atoms until more detailed retention
experiments have revealed the differences between the absorption of methyl iodide
and of mercury which might be expected if the regional sites are indeed distinct.
Regional deposition of particles remains a major outstanding problem and little
progress has been made towards its elucidation since 1960. It is unlikely that a theo­
retical approach can throw any light upon the subject unless it takes full account
of the viscous nature of the flow through the bronchi and bronchioles. This governs
the depth of penetration of inhaled air into the alveolar ducts and determines, in the
shape of hundreds of thousands of apices of the paraboloidal envelopes of an inha­
lation, the surface over which transport of particles from tidal to alveolar air is ef­
fected. Although prevailing theories, based on the idea of deposition from flow through
tubes or filters in series, can be adjusted to give plausible particle size deposition
curves, they are inadequate models of the real processes.
It is a characteristic of viscous flow that it is reversible on account of the negli­
gible influence upon the flow pattern of the mass of the fluid. There is thus a tendency
for the streamlines of flow during exhalation to recapitulate, in a reversed direction,
those of breathing in. The exchange mechanisms, which enable particles or vapours
to move across the streamlines, would then represent the only method of transport
from tidal air to alveolar air. If the airways of the lungs had fixed bopndaries, and
the expansion and contraction of all the alveolated parts proceeded in unison, this
would be true and the kinetics of flow during exhalation would recapitulate in detail
the process of inhalation.
In fact, neither of these suggestions is correct. The calibre of the airways changes
rhythmically and the order of emptying different parts of the lungs may not be exactly
the reverse of the order of filling. Just how much these phenomena may upset the
reciprocity of tidal ebb and flow, and superimpose a mechanical mixing of bulk
aerosol upon the individual mobility of the particles, is not certain. A few experiments
in which a small volume of stable aerosol was introduced into an inhalation of air so
that the rise and fall of concentration was very sharp, revealed upon exhalation
remarkably little blurring of the concentration profile so that mechanical mixing
has probably a fairly small influence on the mingling of tidal and alveolar air which
is mainly due to gas diffusion.
The diffusive transfer of oxygen and carbon dioxide readily transports the gases
diametrically across the alveoli, the alveolar sacs, atria and ducts and even longitudi­
nally up the lumen of the fine peripheral airways to reduce the gas dead space by an
appreciable volume. It looks as though the influence of the gas diffusive motion upon
aerosol particles which are suspended in the alveolar regions is rather small; the par­
ticles trace out the fluid mechanical motions of the suspending gas, but not the diffu­
sion of its constituents. Superimposed on the gas flow the particles have their own
diffusion, which is very much slower than gas diffusion, their sedimentation under
gravity, and their drift by inertia which is negligible in the alveolar regions.
Preface Xlll
Uncertainty continues about the proportions of inhaled particles of different sizes
which deposit in the alveolated regions of the lungs, beyond the terminal bronchioles.
During the last five years the size distribution of lung dust has been studied in detail;
there is no doubt that this dust is considerably finer than the airborne dust which
was inhaled and the peak of the distribution by weight is always below, and often
far below, 1·5 μ diameter. Theoretical interpretation, in the present volume, of earlier
human inhalation experiments by Altshuler and his colleagues (Arch. Ind. Health
15, 293, 1957) leads them to conclude that maximal lower respiratory tract deposition
occurs at a much larger size, between 1-6 μ and 3-2 μ. which is extended to a possible
6 μ in the discussion. If this is correct it means that elimination of deposited dust
from the walls of the alveoli must be biassed towards the larger particles; of this there
is no evidence whatsoever. Calculation of the quantity of dust which would be in­
haled, say by a coal miner working under average conditions, indicates that were his
alveolar deposition to operate according to the curves on pages 332 and 333 then the
rate of elimination from the alveoli must be both selective and considerable. Experi­
ments, such as those of Stöber and his colleagues (page 409) suggest that human
alveolar clearance is slow and that the bulk of lung retention is in the alveoli where
a steady state ensues, after some 20 years of exposure, with the rate of alveolar depo­
sition balanced by the rate of elimination from the alveolar surface, presumably
to the bronchial epithelium; the amount found in the lymph nodes was relatively
small.
A good deal of effort has gone into the use of gamma-emitting particles in attempts
to reveal the mechanics of bronchial elimination. The main difficulty is the extremely
rough collimation of the crystal counter which is exacerbated by experimental tech­
niques using non-homogeneous aerosols and maintaining no control on breathing
pattern. These last points, which are important, are relatively easy to resolve but
the uncertainty about the precise part of the subject's anatomy which is being counted
is fundamental and involves a delicate balance between the permissible dose of in­
haled radioactive aerosol and the sacrifice of sensitivity in counting by better collima­
tion. No doubt, a few more years of progress in crystal counters will ease the situation.
Recent indications are that particles are able to delay for a considerable time on or
in the bronchial epithelium. This was not previously suspected; if it is correct, then
long term chest activity does not necessarily come from radioactive particles in the
alveoli. Differentiation between bronchiolar and alveolar deposition depends on par­
ticle size and tidal volume. Uncertainty about size has already been mentioned; the
lack of concern with tidal volume, and the use of too large a tidal volume to ensure
bronchiolar deposition, indicate a lack of appreciation of the fluid mechanics of
viscous flow.
The volume of the airways down to the base of the terminal bronchioles may be
taken as 200 cm3; this is the anatomical dead space. This volume is less than that
given by the writer in the 1961 book (page 84) owing to recent improvements in the
anatomical scheme. If, now, 200 cm3 of air is breathed in, the advancing tips of
the envelope of inhaled air actually attain a depth up to which the airway volume is
nearly 500 cm3. This is due to the parabolic flow contour which results in axial air
advancing more rapidly, and further, than air near the airway walls. Some 50 cm3
XIV Preface
of a tidal volume of 200 cm3 thus penetrates into alveolated regions. In order to be
sure that no particles can deposit directly into the alveoli a tidal volume of only
100 cm3, or less, is necessary.
It is clear that more exact knowledge of the behaviour of the mucociliary epithelium
is desirable and that the past tendency to regard it as a reliable escalator system needs
examination. The possible existence of areas of stasis, of short circuiting from the
alveoli, of paralysis by inhaled substances and of unsuspected directions of the cur­
rents of mucus flow are aspects of particular interest.
It is shown, for instance, by Proctor and Wagner that in the nose an epithelial
stream exists which is directed backwards towards the nasopharynx. It is, however,
a matter of common observation that dust particles accumulate in the anterior, un-
ciliated part of the nose, just inside the nares, and may be recovered from there some
twelve hours after breathing dusty air. If, in fact, these particles have been brought
up the trachea it seems that an opposite, outwardly directed stream of mucus must
exist as well.
As regards clearance by macrophages from the alveolar regions, a measure of agree­
ment on the general mechanism is being achieved although there is still doubt about
the origin of the cells. A convincing-picture has been drawn by Allison and his col­
leagues of the uptake of particles and, in the case of silica, the attack on the phagosome
membrane leading to the death of the macrophage; a plausible explanation of the
protective action of polyvinyl pyridine-N-oxide fits in with this.
There is an indication, from the work of Strecker, that the fraction of dust deposited
in the alveoli which finds its way into the lymphatic system does so by virtue of its
damaging action upon the macrophages which mop it up. He supports the view that
macrophages originate from the alveolar wall where there is a sufficiently rapid turn­
over of cells to support a pool of phagocytic cells. This, however, is not the view of
Collet and other French histologists who deduce an extrapulmonary origin, on evolu­
tionary grounds, possibly in the lymphoid tissue. Nor is there universal acceptance of
the role of lymphatic clearance which Stöber, Einbrodt and Klosterkötter regard as
an attempt to take care of dust particles which have succeeded ih penetrating the
alveolar walls; these enter lung tissue, to be stored in dust foci and granuloma, and
it is supposed that it is to this fraction of deposited dust that lymphatic clearance is
specifically directed.
Both in this volume and its predecessor it is only too evident that pressures, which
are completely understandable, are an insidious temptation to us to forget our class­
ical scepticism and act like normal human beings. Immured by a complex of irrele-
vancies, our resolution is undermined. For me, the chief lesson of this collection of
papers is the validity of the simple, isolated experimental fact.
London School of Hygiene and C. N. DAVIES
Tropical Medicine
May, 1966
UTILISATION DU CHAT DANS L'ÉTUDE
EXPÉRIMENTALE DES PNEUMOCONIOSES
A. POLICARD, A. COLLET and C. NORMAND-REUET
Centre d'Études et Recherches des Charbonnages de France, Verneuil-en-Halatte
(Oise)
Abstract — Among mammals with a bronchial system comparable to that of
man, cats are distinguished by their small size and relatively low price.
Rather short bronchioles prolonged by a very extensive ramifications of alveo
lar ducts are coated with a cubic non-ciliated epithelium without goblet
cells.
The bronchi differ greatly from those of rodents commonly used, owing to
their large number of glands originating in the neighbourhood of the cartilaginous
bronchi. A large number of smooth muscle fibers are observed in the region of
the alveolar ducts.
Short exposures reveal the places where dust cells first force their way towards
the interstitial spaces and their motion up to the subpleural interstices. Prolonged
dust exposures show the formation of perivascular and peribronchiolar deposits
which are very similar to those found in man. In some cases it was possible to
observe true dust nodules.
INTRODUCTION
LORSQU'ON étudie les réactions biologiques vis-à-vis des particules minérales à
l'échelle de la cellule ou du tissu, on constate des variations d'intensité d'une espèce
animale à l'autre. Par exemple, l'épiploon du Rat se révèle considérablement plus
sensible au quartz que celui du Cobaye. Il s'agit là de modifications quantitatives et
non qualitatives. Mais lorsque l'on doit observer des phénomènes physiopathologi-
ques au niveau d'un organe, tels que la disposition des particules au cours de l'in­
halation et leur cheminement dans les structures pulmonaires, il est indiqué d'utiliser
des animaux possédant un système bronchique et alvéolaire aussi voisin que possible
de celui de l'Homme. Le détail des processus et l'importance de chacun des facteurs
mis en jeu ne pourront être extrapolés avec sécurité qu'à partir d'un organe semblable
au nôtre, soumis à un empoussiérage comparable à celui des environnements in­
dustriels.
Le Singe était dans ces conditions tout particulièrement désigné. Mais il présente
des difficultés évidentes relatives à son élevage, son entretien et sa manipulation.
Le prix de revient des expériences se trouve par ailleurs fort élevé.
Le poumon des rongeurs se révèle un peu simple en ce qui concerne la disposition
et la structure des terminaisons bronchiques. Celui du Chien possède une complexité
suffisante, mais la taille de l'animal et son prix représentent des difficultés assez
3
4 A. POLICARD, A. COLLET and C. NORMAND-REUET
grandes. Réputé peu sensible à la silice (GARDNER, 1938), il a été de fait très peu
utilisé dans une période plus moderne.
Parmi les animaux commodes quant à leur taille, leur prix et leur approvisionne­
ment et possédant un système bronchique convenable, nous avons pensé que le Chat
était un animal de choix (POLICARD et Û/., 1964). Cependant, il semble n'avoir été
utilisé que dans de très rares occasions pour l'étude expérimentale des pneumoco-
nioses (OTTO, 1925), malgré l'opinion favorable de GARDNER (1938) pour qui le
grand champ pulmonaire du Chat constituait un matériel excellent pour les examens
radiologiques.
Nous désirons dans cette note décrire les caractéristiques de l'appareil respiratoire
du Chat et montrer que ses réactions aux poussières se rapprochent beaucoup de
celles que l'on peut observer chez l'Homme.
ANATOMIE
La taille du Chat permet une manipulation aisée. De plus, il n'est pas nécessaire
de construire pour lui des cages d'empoussiérage spéciales, les cages utilisées pour
rats et cobayes convenant parfaitement. En outre, une contention chimique (cianatil
ou 7204 R.P.) réduit les difficultés inhérentes à la psychologie particulière de cet
animal.
En ce qui concerne le poumon, le système bronchique et bronchiolaire se trouve
être à peu près aussi compliqué que celui de l'Homme. D'après ENGEL (1959), la
bronchiole respiratoire ne se ramifie qu'une ou deux fois, contrastant avec la richesse
des canaux alvéolaires qui sont, eux, particulièrement développés. S'il n'est pas
exactement superposable à celui de l'Homme, l'appareil des voies aériennes diffère
considérablement de celui des Rongeurs chez lesquels les canaux alvéolaires et les
bronchioles sont relativement courts, la bronche à epithelium cylindrique faisant
rapidement suite aux sacs alvéolaires.
On remarquera que l'épithélium cubique revêtant les bronchioles, d'abord continues
puis alvéolisées, est dépourvu de cils vibratiles et de cellules caliciformes. Ces deux
éléments demeurent liés à l'épithélium cylindrique, caractéristique des bronches.
La base des cellules bronchiolaires renferme parfois du glycogène en abondance.
Des phénomènes physiologiques se superposent à ces structures anatomiques. La
fréquence respiratoire d'environ 26 par minute, jointe à un volume d'air courant
voisin de 12,4 ml (LUMB, 1963), crée un régime aérodynamique plus proche du nôtre
que la fréquence élevée des Rongeurs, mobilisant de très faibles volumes d'air (90 et
1,8 ml pour le Cobaye (LUMB, 1963).
ENGEL (1959, 1964) a souligné à juste titre le développement considérable des
glandes bronchiques et trachéales du Chat. Nous avons observé cependant que
celles-ci n'apparaissent pas dans les bronches les plus petites avec epithelium cylin­
drique, mais à un niveau supérieur, juste à la ramification conduisant aux bronches
avec cartilage.
Les glandes sont de type acineux, du type qu'on appelait cellules muqueuses
fermées, contenant de nombreuses granulations PAS positives. Le microscope élec­
tronique y montre des cellules pauvres en ergastoplasme, avec des grains de sécrétion
FIG. 1. Cytologie infra-microscopique d'une glande bronchique. Notez la présence des grains
de sécrétion et l'importance des desmosomes.
FIG. 2. Fibres musculaires lisses sous un revêtement alvéolaire normal appartenant probable­
ment à un canal alvéolaire.