EPIDEMIOLOGY
OF ASBESTOS-ASSOCIATED DISEASES
CHRONIC
PULMONARY DISEASE. ROLE OF ASBESTOSIS
-
Kaz
Shimada 5/26/94
1. Introduction
Asbestosis is a pulmonary disease of extremely long evolutionary
process. One of its characters is
that it is caused by an inorganic agent.
Another is that it causes non-granulomatous lesion [TABLE 211-1]. Macrophage contributes to the
pathogenesis of the disease [FIGURE 211-1]. Asbestos-associated diseases, which include asbestosis, will
be described in this paper, emphasizing epidemiological aspects.
2. Definition
\Asbestosis is a diffuse interstitial fibrosing disease of the lung
that is directly related to the intensity and duration of exposure.
\Asbestosis is reserved for the parenchymal disease caused by
asbestos. Other asbestos-related
disorders are: asbestos-induced
pleural disorders, asbestos-induced mesothelioma, asbestos-induced airway
dysfunction, and asbestos-induced lung cancer.
3. Agent
\Asbestos is a kind of inorganic dust [FIGURE 2].
\Asbestos refers to the commercial product after mining and
processing; it is a family of
several different fibrous hydrated silicates, including chrysotile (90%),
amosite, anthophyllite, and crocidolite [FIGURE 1].
\Asbestos is mainly produced in former Soviet Union, China, Canada,
and South Africa. In U.S., Vermont
and California have mines.
\Usage of asbestos
Because
of its exceptional thermal and electric insulation properties, asbestos is used
in cement piping for water mains and sewage lines (25%), construction material,
fire-smothering blankets, safety garments, filler for plastic materials, in
cement and floor tiles, and in friction materials, such as brake (especially
automobile drum brake lining) and clutch linings, and missile fuel system,
structure coating for fire resistance (see below), etc.
Worldwide
utilization of asbestos increased dramatically between 1940 and 1970 [TABLE
1]. Starting in 1975 it
has been mostly replaced with fiberglass or slag wool.
Asbestos
is still used in the manufacture of brake linings, and will remain in buildings
and ships, especially in developing countries where use of it is widespread.
Pathogenicity - asbestosis
\Exposure to any of the asbestiform fiber types will result in
pulmonary fibrosis.
\Chrysotile fibers have large aerodynamical cross-sectional diameter,
so they tend to be deposited more proximally. Thinner and straight fibers will lodge in the terminal
airways.
\Because of their shape, asbestos fibers can persist in the lungs for
many years after inhalation, so a single fiber may activate a series of
macrophages over a long period of time.
This may explain why there
is often a long latency period between exposure and the development of
asbestosis and why the disease can continue to progress for up to 20 years
after exposure has been discontinued.
\The bulk of the fibers is removed by the mucociliary escalator. Short fibers are ingested by
macrophages. The epithelial cells
also take up fibers. About half
the asbestos is removed within a few days. The bulk of this material is excreted in the feces.
\During phagocytosis of the asbestos fiber, the membrane of the
macrophage is damaged, which results in the release of lysosomes containing
enzymes that may act to damage (fibrogenic factors are released) the lung
parenchyma.
\Also accumulation of leukocytes and the release of lysosomal enzymes
after asbestos activated complement by the alternative pathway, and possible
stimulation of the production of collagen are considered in the
pathophysiology.
\The clinical manifestations are typical of those physical findings
in any patient with pulmonary
fibrosis.
Pathogenicity - bronchogenic carcinoma
\Since asbestos is not a potent mutagen, it is suggested that
asbestos increases the susceptibility of epithelial cells of the bronchi and
their branches to transformation by carcinogens in the environment.
\Asbestos fibers may serve as a physical carrier of the carcinogens
in cigarette smoke to the basal cell, the presumptive progenitor of the
neoplasms.
Other naturally occurring asbestiform material
\In central Turkey, population exposed to volcanic rock (erionite, a
fibrous zeolite) had an excess incidence of lung cancer and mesotheliomas.
Man-made mineral fiber (MMMF)
\No cases of mesotheliomas from MMMF without exposure to asbestos
have been reported.
4. Host
\Approximately 9.1 million workers in US who had exposure to the
various forms of asbestos fibers were estimated to be alive in 1980 and
therefore subsequently at risk of asbestos-related diseases.
\Direct exposure
Occupations
of asbestos exposure include mining, milling, and manufacturing of asbestos
products, pipe fitters, boiler makers, and other workers in the building
trades, fire-resistant fabric production, automobile/aircraft industry, and
demolition workers.
\Indirect exposure
Cases
of asbestos-related diseases have been encountered among:
painter or electrician who works
alongside the insulation worker in a shipyard,
housewife who does no more than shake
out and wash her husbandÕs work
clothes,
residents in the neighborhood of an
asbestos plant in London and in the
communities near asbestos mines in South Africa (mesothelioma cases).
Community
exposure has probably resulted from the use of asbestos- containing material
sprayed on steel girders in many large buildings as a safety
feature to prevent buckling in case of fire.
Environment
\Many Americans consume water containing asbestos-like minerals.
\Amphibole asbestos fibers were found in the drinking water of
Duluth, Minn., resulting from the disposal contamination of Lake Superior.
\Asbestos fibers were found in over half the samples of water
studied: Boston (3.98 fibers/liter, Duluth (1.72), New York (0), Philadelphia
(16.95), etc.
\Mineral fibers have been detected in the urine of residents of
Duluth.
5. Epidemiological data
\There is no good answer to the question ÔIs there difference by
fiber types?Õ
Malignant mesotheliomas
\Prevalence of the tumor in workers who have had heavy exposure over
extended periods is about 2 to 3 % and has been reported to approach 10 %.
\More than 80 % of mesotheliomas may be associated with asbestos
exposure.
Bronchogenic carcinoma
\The prevalence of tumors is higher in persons working with the
finished products (such as insulators) than in miners and millers. The severity of the pulmonary
parenchymal fibrosis correlates with an increase in the number of
neoplasms. The incidence of tumors
is also increased in asbestos workers who lack radiologic evidence of
asbestosis.
\A linear dose-response relation between the cumulative dosage of
asbestos and the development of bronchogenic carcinoma has been reported in
miners and millers of chrysotile in Canada and factory workers in the UK.
\Mortality among chrysotile workers is increased 2.4-fold, whereas it
is five times higher than normal among miners of both chrysotile and
crocidolite.
\Bronchogenic carcinoma is uncommon in non-smoking asbestos workers.
\Only a slight increase in the prevalence of lung cancer among
non-smoking workers. Those smoke
more than 20 per day have an 80-fold to 90-fold greater predisposition to
cancer of the lung. Thus, the
combined effects of asbestos and smoking appear to be multiplicative rather
than additive.
Extra-pulmonary cancers
\Asbestos is implicated in the causation of cancer in the upper and
lower gastrointestinal tract and the kidney. Oropharyngeal and esophageal tumors occur more frequently in
asbestosis workers who smoke.
\Twofold to threefold increase in the prevalence of tumors of the
digestive tract in insulators, factory workers, and shipyard employees is
reported.
\It is suspicious that peritoneal mesotheliomas have been confused
with metastatic carcinomas of gastrointestinal-tract origin in death
certificate data.
\Asbestos migrates to the kidney.
\The animal and post-mortem studies suggest that ingested asbestos is
disseminated to abdominal organs by the lymphatics and blood vessels.
6. Natural history of the disease
Asbestosis
\Usually at least 10 years of moderate to severe exposure has
occurred before the disease becomes manifest. It develops slowly over a period of years and seems to
progress in the absence of continued exposure to asbestos.
\Except for a history of exposure to asbestos, asbestosis resembles
the other forms of diffuse interstitial fibrosis.
\Initially, fibrosis is found in and around the respiratory
bronchioles and alveolar ducts, where relatively long fibers deposit. With time, the fibrotic lesion
progresses in a seemingly centrifugal manner.
\Fibers of asbestos tend to accumulate preferentially in the lower
lobes and adjacent to the visceral pleura. Fibrosis is usually prominent in these regions.
\An early sign of severe disease may be a reduction in diffusing
capacity.
\Spirogram shows a restrictive pattern with a decrease in lung
volumes.
\X-ray reveals pleural plaques [pleural lesion is differentiated from
asbestosis] for past exposure (not pulmonary impairment). Radiographic diagnosis of asbestosis
depends upon the presence of irregular or linear opacities.
\Ferruginous bodies (asbestos bodies) are the histologic hallmark of
exposure to asbestos. Ferruginous
bodies in most human lungs have asbestos as a core.
\No specific treatment available.
\Strongly recommend cessation of smoking to avoid cancer.
Lung cancer
\Lung cancer is the most frequent cancer associated with asbestos
exposure.
\15~19 years between first exposure and development of disease.
\Adenocarcinomas predominate.
\If a smoker, sputum cytologic examinations and repeated chest x-rays
as frequently as every 4 to 6 months will detect early stage cancer.
Mesotheliomas
\No association with smoking.
\Both pleural and peritoneal.
\This is of particular concern from a public-health standpoint
because persons who have had either transient (1~2 years) or indirect exposure
to asbestos will have disease some 20 ~ 25 years after the exposure.
\Peak dormant period is 30 ~ 35 years.
\Death usually results from local extension although there is 50 %
chance of metastasis.
\Effusion may obscure the underlying pleural tumor.
\Documented mesothelioma in a worker with occupational exposure to
asbestos may be compensable in many parts of U.S.
7. Prevention
Standards
\Recommendation for levels of asbestos in the air of occupational settings in U.S. was
formulated in the 1940s.
\Federal regulations were promulgated in 1970.
\1970 standard was 5 fibers /cm3 air, fibers 5µm or
longer counted by light microscope, averaged over 8 hour period, with
stipulations for transient excesses above that concentration.
\1976 standard is 2 fibers/cm3.
\0.5 fiber/cm3 is proposed.
Problems in establishing standards
\Establishment of standards for air quality in the work place is very
difficult because of the necessity to use data on morbidity and mortality, and
the long latency period of asbestosis and the asbestos-associated cancers.
\The dust concentrations permitted by current regulations will
probably not induce substantial pulmonary fibrosis during the lifetime of an
industrial worker.
\Standards are based on extrapolations from data accumulated among
workers exposed to relatively heavy concentrations of dust in the past. No threshold level is assumed.
\Risk for the nonsmoking asbestos worker is substantially lower than
the risk for a member of the general population who smokes two or three packs
of cigarettes each day.
\The conclusion that asbestosis fails to develop below a certain
threshold dosage is based on physical examinations and radiologic studies of
workers and not on pathological examinations.
8. Liability
\12,000 suits have been brought against 260 companies (1982).
\Federal government is involved for alleged negligence in
establishing adequate environmental standards.
References
1) Wilson
JD, Braunwald E, Isselbacher KJ, et al. ed. Principles of internal medicine,
12nd ed. New York, McGraw-Hill, 1991.
2) Craighead
JE, Mossman BT. The pathogenesis of asbestos-associated diseases. The
New England journal of medicine; 306: 1446 - 1455, 1982.
3) LaDou
J. Occupational medicine. Norwalk, Appleton & Lange, 1990.
* No reference in MMWR after 1988.
|
|