Asbestos-Related Disease

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Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK; Sarah Al Ghanem, MBBS, Consulting Staff, Department of Medical Imaging, King Fahad National Guard Hospital, Saudi Arabia; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Carolyn M Allen, MB, BCh, MRCP, FRCR, CCST, Consultant Radiologist, Department of Clinical Radiology, North Manchester General Hospital, UK
Contributor Information and Disclosures

Asbestos is a naturally occurring, fibrous silicate that was widely used in the past for commercial applications because of its heat-resistance properties. Asbestos exists in several forms. The 2 primary groups of asbestos are made up of amphibole and serpentine fibers. Amphibole fibers, which are characteristically straight, rigid, and needlelike, can be subdivided into commercial amphiboles (crocidolite, blue asbestos, and amosite [brown asbestos]) and noncommercial amphiboles (actinolite, anthophyllite, and tremolite). Chrysotile (white asbestos) is the only form of serpentine asbestos that is used commercially, and it accounts for more than 90% of asbestos used in the United States.1
For the most part, asbestos exposure has been industrial or occupational; such exposure primarily affects workers involved in mining or processing asbestos or those involved in the use of asbestos in the shipbuilding, construction, and textile- and insulation-manufacturing industries.2, 3 Chrysotile is mined in Canada, and tremolite and anthophyllite are mined in Finland and North America. Crocidolite and amosite are mined in South Africa and Australia. About 2-6 million people in the United States are estimated to have had significant levels of exposure.3, 4

High exposures ceased in the United States in the late 1970s, and later in the United Kingdom, because of governmental legislation passed after the adverse effects became recognized. However, because the latency period between an initial exposure and the development of most asbestos-related disease is 20 years or longer, asbestos-related disease remains an important public health issue.5, 6

The spectrum of asbestos-related thoracic diseases includes benign pleural effusion, pleural plaques, diffuse pleural thickening, rounded atelectasis, asbestosis, mesothelioma, and lung cancer.7

Asbestosis is defined as diffuse lung fibrosis due to the inhalation of asbestos fibers, and it is one of the major causes of occupationally related lung damage. Mesothelioma is a malignant pleural or peritoneal tumor that rarely occurs in patients who have not been exposed to asbestos.8, 9, 10, 11, 12, 13

The diagnostic approach to asbestos-related intrathoracic disease is different from that of other diffuse lung diseases because of the medicolegal implications.14 The likelihood of asbestos-related disease should be determined, and other possible causes should be eliminated. An assessment of the extent of disease is used to calculate compensation. Therefore, imaging plays a pivotal role in the diagnosis and management of asbestos-related disease.

See also the following related eMedicine topics:

Asbestosis [Pulmonology]

Asbestosis [Radiology]

Mesothelioma

Mesothelioma, Malignant

Peritoneal Cancer


Pathophysiology

Physical properties of asbestos fibers

Evidence regarding the relative importance of the different physical properties of the asbestos types in causing disease is conflicting.15, 16 Certainly, fine fibers are more pathogenic than are thick fibers. Fibers of 5 µm or more in diameter tend to become deposited in larger airways, from which they are effectively cleared through mucociliary action. In comparison, fibers that are more slender tend to be deposited in small airways or airspaces, from which only a proportion of them are cleared.

The effect of fiber length is less certain, but straight fibers that are approximately 5-20 µm long, such as crocidolite fibers, are not cleared as effectively as others are, and they can cause intense inflammation and fibrogenic changes within the interstitium. Conversely, chrysotile fibers are flexible, they usually do not fragment, and they are longer than 100 µm; therefore, they tend to be deposited in major airways, from which they are cleared to a large extent.

Despite differences in their physical properties, all types of asbestos fibers are fibrogenic. However, crocidolite is the most carcinogenic.

Pathogenesis

The pleurae are more sensitive than pulmonary parenchyma to the effects of the fibers. Thus, pleural plaques develop after low, intermittent exposure, whereas asbestosis is associated with cumulative, high-level, long-term, continuous exposure in association with a definite dose-effect relationship. Nonmanual workers in industries involving asbestos, inhabitants of areas immediately surrounding asbestos mills, and families of asbestos workers have an increased incidence of mesothelioma. However, even with significant industrial exposure, asbestosis is unusual.

Pleural plaques are the most common manifestation of asbestos exposure, occurring after a latent period of approximately 20-40 years. A history of exposure can be elicited in more than 80% of patients. Histologically, pleural plaques consist of acellular collagen bundles that form a basket-weave pattern, which almost exclusively involves the parietal pleura. The plaques may contain chrysotile asbestos fibers.

The precise pathogenesis of pleural plaques remains undetermined. That they are caused by the mechanical effect of asbestos fibers piercing the visceral pleura (the scratching theory) was assumed. Currently, however, the fibers are believed to be transported to the parietal pleura via lymphatic channels, where they incite an inflammatory response. Plaques slowly grow over time, even after cessation of exposure, but they are not considered premalignant.

Calcification occurs later, often 30-40 years following exposure. Pleural plaques tend to occur in isolation without any other manifestations of asbestos-related disease; however, the converse is not true. Asbestosis is rarely seen in the absence of plaques.

Diffuse pleural thickening is less specific for asbestos exposure than is the presence of pleural plaques, since thickening also may be seen following tuberculous (TB) pleuritis, hemothorax, and empyema. Usually, the latent period is approximately 15 years. The pathogenesis is unclear, but it is believed to be due to inflammation and fibrosis of the visceral pleural lymphatics, and it has been considered to be an extension of parenchymal fibrosis. Histologically, the appearances are similar, although in diffuse pleural thickening, fusion of the visceral and parietal layers and asbestos bodies (which are absent in pleural plaques) is profuse. Development of diffuse pleural thickening has a similar time line as plaque formation.

Benign, asbestos-related pleural effusions are often the earliest manifestation of asbestos-related disease, typically occurring within 10 years after exposure. The effusions are exudative. Occasionally, they are hemorrhagic, but otherwise, their features are nonspecific. Effusions tend to be self-limiting, with a duration of a few months, but they can be chronic or recurrent. Diffuse pleural thickening not uncommonly develops following resolution of the effusion.17, 18, 19

Fibers not cleared by mucociliary action are believed to be transported into the interstitium, where they form aggregates, usually at the level of the respiratory bronchiole. Research results suggest that the fibers stimulate the release of a collagenase inhibitor–like protein that locally disturbs the balance of collagen turnover, resulting in fibrogenic changes within the interstitium.

Asbestosis is usually seen when levels reach 10 million asbestos fibers per gram of pulmonary tissue. Asbestosis characteristically occurs following a latent period of 15-20 years, with a progression of disease even after exposure has ceased. Fibrosis first arises in and around the respiratory bronchioles, predominating in the subpleural portions of the lung in the lower lobes. This progresses to involve the alveolar walls, eventually causing honeycombing in a minority of patients.

Folded lung (also termed round atelectasis, pulmonary pseudotumor, or Blesovsky syndrome) specifically refers to an area of atelectatic lung adjacent to pleural thickening, with characteristic in-drawing of bronchi and vessels. Blesovsky first reported folded lung in 1966. Although folded lung is strongly associated with asbestos exposure, it may also be seen as a consequence of any inflammatory or infective organizing pleural exudate.

The presence of the effusion has been postulated to cause passive atelectasis, with infolding of the lung resulting in invagination of the adjacent pleura. This process causes tethering, which prevents reexpansion of the lung upon resolution of the effusion and which causes round atelectasis. A more accepted alternative explanation is that an insult to the pleura leads to localized inflammation and fibrosis, which results in volume loss and buckling of the underlying lung. Interestingly, the changes have been shown to resolve after decortication. The lingula is the most common site, followed by the middle and then the lower lobes, although lesions may be multiple and bilateral.

Malignant pleural mesothelioma is a rare neoplasm, accounting for less than 5% of pleural malignancies. Malignant pleural mesothelioma is strongly associated with asbestos exposure, particularly crocidolite exposure; however, the association does not appear to be dose-related, because significant numbers of cases occur after trivial environmental or household exposure. No relevant history of any asbestos exposure is found in 20% of patients. The disease is frequently seen in the absence of any other manifestations of asbestos exposure and usually develops after a long latent period of 35-40 years.

Mesothelioma is 80% pleural and 20% peritoneal in origin. Pleural effusions are not a precursor of mesothelioma, but they often antedate development of malignancy. A confident diagnosis is often difficult to make and usually requires ultrastructural analysis and histochemical and immunohistochemical tests. Histologically, 3 forms of malignant mesothelioma are recognized: epithelial, mixed, and sarcomatous (also known as mesenchymal). These must be differentiated from mesothelial hyperplasia and metastatic adenocarcinoma. The most common histologic subtype is epithelial, accounting for 50% of cases.

Bronchogenic carcinoma is estimated to develop in 20-25% of heavily exposed asbestos workers. Smoking has a cumulative effect, further increasing the risk of lung cancer to a factor of 90 versus a factor of 5 in exposed nonsmokers. Often, asbestos-related interstitial disease is associated; however, no correlation exists between the severity of asbestosis and the development of lung cancer. Furthermore, lung cancer has been reported in individuals without interstitial lung disease who have been exposed to asbestos. A latency period of 25-35 years is usual. Histologically, the predominant subtype is broncho-alveolar cell carcinoma, but adenocarcinoma and squamous cell carcinoma also occur.

Associations between asbestos exposure and other cancers—including carcinomas of the larynx, esophagus, stomach, and colon, as well as a variety of lymphoid malignancies—have been reported anecdotally.

See also the following related eMedicine topics:
Atelectasis
Atelectasis, Lobar
Atelectasis, Pulmonary

Frequency

United States

The number of individuals affected by asbestos-related disease is slowly increasing. However, whether this is secondary to a true increase in incidence or due to increased recognition is debated.

The prevalence of benign pleural plaques in the non–asbestos-exposed general population is extremely low. The prevalence in environmentally exposed general populations in industrial societies is approximately 0.5-8%. Frequencies in exposed individuals are 3-58%, depending on occupation. The development of plaques depends on the length of exposure or the amount of time that has passed since the first exposure, as opposed to being dependent on a threshold dose, which is the case for asbestosis. The prevalence of pleural plaques is 10% in exposed individuals 20 years after exposure, rising to 50% after 40 years.

The prevalence of diffuse pleural thickening is not known, although it is reported to occur with frequency equal to that of pleural plaques. Thickening is a common concomitant finding to asbestosis, with a reported associated incidence of 10%.

The frequency of benign, asbestos-related pleural effusions in exposed individuals is reported to be 3-7%. However, this number may be an underestimate, because most patients are asymptomatic; therefore, effusions are subclinical and undetected. The incidence rises with increasing levels of asbestos exposure.

Asbestosis is reported to develop in 49-52% of adults with industrial asbestos exposure, after a latency period of 40-45 years.

Approximately 2000-3000 cases of malignant mesothelioma, or 7-13 cases per million general population, are diagnosed annually in the United States.

Epidemiologic studies predicted a decline in incidence in the United States after the year 2000, with a peak incidence in the United Kingdom in 2020. The prediction is probably applicable to benign pleural plaques also, because the latency period is similar. Lung cancer develops in as many as 25% of asbestos workers. In asbestos-exposed nonsmokers, the incidence of lung cancer is 5 times that of the general population. In exposed individuals, smoking further increases the risk of bronchogenic carcinoma by 80-90 fold.

International

The incidence of asbestos-related lung and pleural disease in the remainder of the industrialized world remains similar to that of the United States. In the United Kingdom, asbestos use was highest in the 1970s, later than in the United States; therefore, the peak incidence of disease lags as well. Legislation regarding asbestos varies from country to country, and although crocidolite is rarely used internationally, other forms of asbestos remain in use.

Mortality/Morbidity

After the onset of symptoms, severe asbestosis may lead to respiratory failure and death over 12-24 years. Respiratory failure may be accelerated by the development of Caplan syndrome; pulmonary hypertension; or malignancy, including lung cancer or mesothelioma.

No treatment for asbestosis is effective. The primary strategy is prevention, through the worldwide elimination of asbestos use and the replacement of asbestos with safe synthetic products.

Mesothelioma tends to appear late and is usually associated with an extremely poor prognosis. The median survival is 10 months or less, and most patients die within 2 years.20


Race

No race predilection exists for asbestos-related disease.

Sex

Mesothelioma has a male-to-female ratio of approximately 4:1. Asbestos-related disease in women is uncommon and is usually confined to spouses of industrial workers, as well as to secretarial and domestic staff working in asbestos industries.

Age

A minimum latency period of 8-10 years is required for an asbestos-related pleural effusion to develop; this is usually the earliest manifestation of asbestos-related disease. Similarly, a latency period of more than 20 years is required for the development of asbestosis. As a result, most patients with asbestos-related disease are older than 40 years.

Mesothelioma usually is seen after a longer latency period, with most patients in the sixth-to-eighth decades of life.

Presentation

Pleural plaques are not reported to cause symptoms.
Diffuse pleural thickening may be associated with symptoms and signs comparable to those arising from other causes of fibrothorax, such as dyspnea. The restriction of lung function rarely may be severe enough to warrant decortication of the lung.
The clinical picture in benign, asbestos-related pleural effusion varies from asymptomatic patients to patients with an acute episode of pleuritic chest pain and pyrexia.
Asbestosis may cause an insidious onset of progressive dyspnea in addition to a dry cough. Clinical findings of basal inspiratory crackles associated with reduction in vital capacity and diffusion capacity are also seen.
Asbestosis is usually diagnosed on the basis of certain clinical, functional, and radiographic findings outlined by the American Thoracic Society (ATS).21 However, these guidelines have not been updated since the routine clinical use of high-resolution computed tomography (HRCT) scanning began in the early 1990s.22, 23 Findings based on the ATS criteria include the following:
Reliable history of nontrivial asbestos exposure
Appropriate interval between exposure and detection (usually >10 y)
Abnormal chest radiographic findings
Restrictive lung disease as indicated by pulmonary function test results
Abnormal diffusing capacity
Bilateral crackles at the lung bases that are not cleared by coughing
Clinical symptoms in malignant mesothelioma are frequently present 6-8 months prior to diagnosis. Symptoms include localized chest wall pain and weight loss. Cough and dyspnea may also be present.
The international staging system for malignant mesothelioma is as follows:

Tumor
T1a - Tumor limited to ipsilateral parietal pleura
T1b - Additional scattered foci of visceral pleural involvement
T2 - T1 plus involvement of diaphragmatic muscle and/or confluent visceral tumor (including fissures) or direct extension to the pulmonary parenchyma
T3 - Locally advanced (but potentially resectable) tumor encasing the lung with at least 1 of the following features:
Involvement of endothoracic fascia
Extension into mediastinal fat
Solitary focus of chest wall invasion
Nontransmural involvement of pericardium
T4 - Locally advanced, unresectable tumor encasing the lung, with at least 1 of the following features:
Multifocal or diffuse chest wall involvement
Transdiaphragmatic peritoneal spread
Direct extension to contralateral pleura
Involvement of vital mediastinal structures
Direct extension to the spine
Transpericardial disease, with or without pericardial effusion or myocardial involvement
Node
N0 - No regional nodal metastases
N1 - Ipsilateral bronchopulmonary or hilar nodal enlargement
N2 - Ipsilateral mediastinal (including internal mammary) or subcarinal nodal enlargement
N3 - Contralateral mediastinal, contralateral internal mammary, or supraclavicular nodal enlargement
Metastasis
M0 - No distant metastases
M1 - Distant metastases present
Staging
Stage Ia - T1a, N0, M0
Stage Ib - T1b, N0, M0
Stage II - T2, N0, M0
Stage III - Any T3, M0; any N1, M0; any N2, M0
Stage IV - Any T4, any N3, any M1
Preferred Examination

HRCT scanning is playing an increasingly important role in the diagnosis of diffuse interstitial lung disease. However, chest radiography remains the initial modality for the detection and characterization of pleural and parenchymal disease. Ultrasonography has a role in characterizing pleural effusions and guiding pleural aspiration and biopsy. Nuclear medicine study has a limited role in the investigation of asbestos-related intrathoracic disease. Gallium-67 (67 Ga) citrate testing has been used to differentiate benign from malignant, asbestos-related pleural disease and to give a quantitative index of inflammatory activity.24

Limitations of Techniques

The limitations of chest radiography in the diagnosis and evaluation of asbestos-related disease are well recognized. The quality of the radiograph and the size, shape, position, and degree of calcification determine whether the radiologist can detect pleural plaques on the image. While the identification of bilateral, scattered, calcified, costal, and diaphragmatic pleural plaques is virtually diagnostic of asbestos exposure, studies have shown an 11% false-positive rate with chest radiographs. In particular, extrapleural fat mimics pleural thickening and is a significant cause of false-positive readings. Conversely, a high false-negative rate has also been reported.

Computed tomography (CT) scans have long been known to be more sensitive and specific than chest radiographs for the diagnosis of asbestos-related pleural disease.25, 26

Radiographic-pathologic studies have shown that chest radiographic findings are normal in as many as 20% of patients with asbestosis. HRCT scanning is more sensitive and specific than other studies, particularly when images are obtained with the patient in the prone position, which allows differentiation of mild parenchymal changes from dependent density (increased attenuation of the posterior, usually basal, lung, which is gravity induced and secondary to nonaeration of dependent alveoli).27

Nuclear medicine studies have been used in small series, but their exact role remains unclear.

Differential Diagnoses

Rib, Fractures

Other Problems to Be Considered

Causes of diffuse pleural thickening

Benign, asbestos-related, diffuse pleural thickening
Postexudative effusion (eg, parapneumonic effusion, connective tissue disease)
Hemothorax
Mesothelioma

Causes of nodular pleural thickening

Malignant mesothelioma
Metastatic adenocarcinoma

Causes of basal subpleural fibrosis

Asbestosis
Usual interstitial pneumonia
Connective tissue disease
Drug-related fibrosis

Causes of a solitary pulmonary mass

Folded lung
Malignancy (eg, bronchogenic carcinoma, metastasis, and lymphoma)
Benign neoplasm (eg, hamartoma and adenoma)
Vascular (eg, arteriovenous malformation, pulmonary infarction, hematoma)
Infection (eg, tuberculosis, round pneumonia, fungal infection)

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