Environmental Health Perspectives Volume
102, Supplement 5, October 1994
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Biopersistence of Respirable Synthetic Fibers and Minerals: Point of
View of the Chest Physician
Paul De Vuyst
Hôpital Erasme, Université Libre de Bruxelles, Route de
Lennik, Brussels, Belgium
Abstract
Problems of diagnosis related to the presence or absence of particles
in lung and pleural tissues are discussed from the clinician's viewpoint.
The advantage of applying mineralogical analytical techniques is considered.
-- Environ Health Perspect 102(Suppl 5):pp-pp (1994)
Key words: pathogenesis, diagnosis, mesothelioma, pulmonary fibrosis,
bronchial carcinoma, biopersistence, asbestos, synthetic fibers
This paper was presented at the Workshop on Biopersistence
of Respirable Synthetic Fibers and Minerals, held 7-9 September 1992 in
Lyon, France.
Address correspondence to Dr.Paul De Vuyst, Hôpital
Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070
Bruxelles, Belgium. Telephone 32 555 31 11.
Introduction
From the chest physician's point of view, problems related to the biopersistence
of respirable particles are linked to the three classical aspects of diseases:
pathogenesis, diagnosis, and prognosis.
Pathogenesis of Dust-induced Diseases
Exposure to minerals, particularly fibers, is associated with three main
severe diseases: pulmonary fibrosis, bronchial carcinoma, and malignant
mesothelioma. It is easily conceivable that prolonged retention of some
types of minerals in the lung would be a stimulating factor for inflammatory
and neoplastic processes, leading in turn to parenchymal fibrosis and peripheral
cancer. The relationship between biopersistence in the deep lung and lesions
of the large bronchi or the parietal pleura is much less evident.
Biopersistence and Pulmonary Fibrosis
Epidemiological and clinical data indicate that those fibers that resist
pulmonary clearance mechanisms, such as crocidolite, amosite, tremolite,
and erionite, are both strongly fibrogenic and carcinogenic. Nevertheless,
there is evidence from clinical practice that exposure to certain types
of nonpersistent particles may also lead to severe chronic diseases, including
lung fibrosis. This is illustrated by the case report of a diamond polisher
who had been exposed to cobalt dust arising from diamond-cobalt polishing
discs, and died from severe lung fibrosis 8 years after the end of exposure.
Analyses of his lung tissue showed only traces of cobalt, as is usually
the case in cobalt- or hard metal-induced diseases. A hypersensitivity factor
certainly plays a role in the pathogenesis of such diseases, and the solubility
of cobalt appears to be an essential factor (1). It is evident that
metallic cobalt is very different from fibrous silica or asbestos. Nevertheless,
for a clinician, this illustrates that even nondurable particles may initiate
inflammatory reactions that lead to parenchymal fibrosis.
Biopersistence and Bronchial Carcinoma
Are the factors of particle respirability and durability in the lung
also relevant for the development of cancer of proximal airways, which are
so easily reached by aerocontaminants? The very large majority of bronchial
cancers that chest physicians encounter are, evidently, due to tobacco smoking,
indicating that repeated and prolonged exposure to what are certainly nondurable
substances may also lead to neoplastic transformation of the bronchial mucosa.
The risk for an ex-smoker to develop a cancer takes more than 10 years to
decrease to the level of a nonsmoker, indicating that definitive effects
were induced before the carcinogenic agents disappeared.
Epidemiological studies show that the risk of bronchial carcinoma is
increased in workers exposed to amphiboles, as well as to chrysotile, particularly
in the textile industry (2), whereas glass fibers and fibers of rockwool
and slagwool, with low durability and respirability are not associated either
with lung fibrosis or mesothelioma (3). It may, however, not be possible
completely to rule out their role in the elevated standard mortality ratio
(SMR) observed for bronchial carcinoma in workers exposed to these latter
fibers in the early industrial phase, when combined exposure to asbestos
was current during that period (4).
Biopersistence and Mesothelioma
Experimental studies, in which animals received intrapleural injections
of fibers, indicate that fibers most carcinogenic for the pleura are thin
(<0.25 µ diameter) and long (>8 µ) (5). Clinically,
malignant mesothelioma develops generally from the parietal pleura, but
little is known about the mechanisms of translocation of asbestos fibers
towards the pleura, nor whether they actually reach it.
In the few studies of pleural fiber burden, mainly small fibers of chrysotile
were found in the parietal pleura. There was, however, no apparent relationship
between the concentration and type of asbestos fibers in the parietal pleura
and those in the lung parenchyma (6,7), perhaps due to complications
resulting from sampling problems. It is probable that exogenous particles
and fibers concentrate in some areas of the parietal pleura, similar to
the anthracotic zones observed during thoracoscopy.
Biopersistence of Synthetic Fibers
Epidemiological studies of large cohorts of workers exposed to insulation
wools have not shown an increased risk of either pneumoconiosis or mesothelioma
(3). The fibers from rock- and slagwool generally have too large
diameters to be respirable, and do not accumulate in the lung. Were synthetic
fibers to be made that were both respirable and biopersistent, they might
well represent a health hazard for the exposed workers.
Diagnosis
Histological Diagnosis
The diagnosis of pneumoconiosis requires the presence of particles in
histological sections; that of silicosis, the association of fibrous nodules
and silica; and of asbestosis, peribronchiolar and interstitial fibrosis
with asbestos bodies. The latter diagnosis depends on the presence of fibrosis
and persistent mineral structures, and these criteria are still considered
necessary for the diagnosis of asbestosis (8). Therefore, even in
asbestos-exposed workers, if histology shows fibrosis in the absence of
asbestos bodies, the preliminary diagnosis would not be asbestosis, and
this could be a recurrent diagnostic problem in the future years because
of the decreasing use of asbestos (especially amphiboles) and the low levels
of dust exposure.
Clinical Diagnosis of Diseases (Mineralogical Analyses)
Chest physicians are rarely well informed about occupational exposure
risks, and are unlikely, therefore, to establish a complete occupational
history of their patients. Moreover, the patient himself may often be unaware
of the risk to which he has been exposed, especially when the disease occurs
several decades after the industrial exposure. These difficulties may be
overcome by analysis of bioindicators, which can be of diagnostic interest
in evaluating dust or fiber retention. Counting of asbestos bodies in bronchial
alveolar lavage (BAL) or in digested lung tissue can be performed routinely
(9), and electron microscopic qualitative and quantitative analyses
of fibrous and nonfibrous particles in lung tissue and lavage are available
for more specific, medicolegal or scientific purposes.
Cause-Effect Relationship. The presence of durable particles
in a biological sample is not in itself a proof that the particles caused
the disease; many factors must be taken into account, including duration
and intensity of exposure, latency delays, and coexistence of other etiological
agents. Nevertheless, a cause-effect relationship will appear more probable
to the clinician when high concentrations of some types of minerals are
found in biological samples, as is illustrated by two clinical observations.
The first patient had been working with crocidolite for a few months during
World War II. Forty-seven years later, he presented with pleural plaques
and a left pleural effusion. Surgical exploration showed benign effusion
with pleural thickening, and the lung biopsy revealed the presence of more
than 7 million fibers of crocidolite/g of dry lung tissue. The persistence
of a high burden of this type of fiber, together with pleural plaques, supported
a diagnosis of benign asbestos effusion.
The second patient, a Turkish migrant from central Anatolia, presented
with lung fibrosis with pleural thickening and calcification. He had never
been occupationally exposed to asbestos, yet BAL yielded more than 1500
asbestos bodies/milliliter, all tremolite. A clinical diagnosis was made
of environmental asbestosis that had arisen in his country of origin since
tremolite was not used in the host country (10).
Influence of Biopersistence. These techniques are evidently
applicable where there has been exposure to biopersistent material. Historically,
in industry, workers were exposed to mixtures of amphiboles and chrysotile.
As the chrysotile fibers are not biopersistent, the residual amphiboles
serve as a marker of total exposure. Nowadays, chrysotile is virtually the
only type of asbestos used so that mineralogical analysis may be of diminishing
interest for diagnosis (11). When we performed BAL analyses on a
group of workers in a brake lining factory who were exposed only to chrysotile
(12), the concentrations of chrysotile asbestos bodies found during
or soon after exposure were comparable to the concentrations of amphibole
asbestos bodies found in asbestos-cement workers. However, when BAL was
performed in one of the patients three years after exposure, a very significant
decrease in concentration of asbestos bodies was recorded, corresponding
to what is known about clearance of chrysotile. A converse illustration
of the influence of biopersistence on diagnosis was the finding of amphibole
asbestos in lung tissue from autopsies of workers exposed to man-made mineral
fibers (13).
Influence of Sampling Site. Malignant mesothelioma can
be associated with lung asbestos fiber concentrations no higher than would
be found in unexposed subjects. Considering the problem of translocation,
it is difficult to see the significance of such a low fiber burden in the
lung and at a considerable distance from the target organ at the time of
cancer progression, perhaps more than 30 years after exposure. Generally,
when mesothelioma is diagnosed, the pleural cavity is full of tumoral tissue,
making it impossible to take a sample of pleura that would yield an analysis
of the mineral content representative of the fiber burden before malignant
transformation. A sample taken from the contralateral side when autopsy
is performed might give a more meaningful result.
Prognosis
A chest physician who is aware of the health risks consequent on exposure
to mineral particles, will probably keep closer watch over patients who
have been so exposed, and even if there is no specific treatment, he may
still be able to restrict exposure to carcinogenic factors, such as smoking.
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