Pulmonary Medicine

Asbestos-related Pulmonary Disorders

What every physician needs to know:

Asbestos-related pulmonary disorders consist of a group of malignant and benign inflammatory-fibrotic disorders associated with exposure to asbestos fibers. The term "asbestos" refers to a group of hydrated magnesium silicate minerals. Since asbestos is almost indestructible and it is both fire resistant and versatile, various types of this material have been used in construction and other industries for many years.

Asbestos has the tendency to separate into fibers, which cause parenchymal and pleural pulmonary disorders when inhaled. These disorders can occur many years after exposure. Asbestos has been the most significant single cause of occupational cancer in the United States and a significant cause of disability and death from benign disease. The pulmonary malignancies associated with asbestos exposure are lung cancer and mesothelioma, while benign asbestos-related diseases include asbestosis, airflow obstruction, pleural fibrosis, and pleural effusions.

In their earliest stages, asbestos-related pulmonary disorders are difficult to detect, and no early intervention has been proven to alter the subsequent evolution of the disease. The general criteria for diagnosis are 1) a clinical syndrome consistent with an asbestos-related pulmonary disorder; 2) A history of exposure to asbestos as documented by occupational and environmental history, or presence of markers of exposure; 3) evidence of pathology consistent with asbestos-related disease, as documented by imaging or histology; 4) exclusion of alternative plausible causes for the findings. The sections below review each of these criteria in detail. The diagnosis of asbestos-related pulmonary disorders has become highly politicized because of litigation related to asbestos exposure.

This chapter focuses on the benign asbestos-related pulmonary disorders. For detailed information on the malignant asbestos-related disorders, see the separate chapters on mesothelioma and lung cancer.

Classification:

The major asbestos-related pulmonary disorders can be divided into diseases of the lung parenchyma and diseases of the lung pleura. Combinations of all of these disorders may be present simultaneously.

Parenchymal diseases

1. Asbestosis is the interstitial pneumonitis and fibrosis caused by inhalation of asbestos fibers. Fibrosis may be localized (asbestomas), but it is more commonly diffuse.

2. Chronic airway obstruction often develops in patients who have a history of asbestos exposure, even without concomitant tobacco exposure.

3. Lung cancers of all subtypes of lung cancer have been associated with asbestos exposure.

Pleural diseases

Pleural abnormalities are the most common manifestation of asbestos exposure.

  1. Pleuritis: Asbestos exposure may cause an acute or subacute pleural effusion that may last for several months.

  2. Pleural fibrosis related to asbestos exposure may be localized (pleural plaques) or diffuse.

    • Pleural plaques, circumscribed areas of pleural thickening, are indicators of exposure to asbestos and are the most common manifestation of the inhalation, retention, and biologic effect of asbestos.

    • Diffuse pleural thickening of the visceral pleura may also occur after asbestos exposure.

  3. Other possible pleural abnormalities related to asbestos exposure include rounded atalectasis (or "shrinking pleuritis"), contracted pleurisy, pleuroma, and Blesovsky's syndrome (or folded lung).

  4. Mesothelioma, a malignant tumor of the pleura, is strongly associated with asbestos exposure.

Are you sure your patient has an asbestos-related pulmonary disorder? What should you expect to find?

As noted above, the first requirement for diagnosis of asbestos-related pulmonary disorders is the presence of a clinical syndrome consistent with an asbestos-related disorder.

The clinical presentation of asbestos-related pulmonary disorders varies depending on which disorder is present; however, more than one asbestos-related disorder may be present simultaneously.

Parenchymal disorders:

Asbestosis: The main symptoms of asbestosis are dyspnea and cough. The classic finding on physical exam is bibasilar inspiratory rales.

The early stages of asbestosis, or asbestos-induced pulmonary fibrosis, may be asymptomatic and may be diagnosed solely on the basis of history and imaging. The first symptom to appear is usually exertional dyspnea followed by cough. When symptoms are present, they are associated with a more accelerated course of disease. The dyspnea in asbestosis has an insidious onset. The cough is usually non-productive, but it may progress to productive cough, especially in patients with concurrent obstructive pulmonary dysfunction (COPD). Wheeze and chronic bronchitis symptoms may be present, also more commonly in those with COPD.

Examination may reveal bilateral inspiratory crackles or rales, usually basilar, which may or may not clear with cough. In the more advanced stages of the disease, clubbing and/or cyanosis may be present. The findings on physical examination have low sensitivity but, when they are present, they are associated with increased risk of mortality.

Symptoms and physical findings alone are not sufficient to diagnose asbestosis; the physician must also establish the presence of pulmonary fibrosis by imaging or pathology and must determine whether asbestos exposure has occurred that is of sufficient duration, latency and intensity to be causal.

Localized parenchymal fibrosis, which is more unusual, results in generally asymptomatic "asbestomas," seen only on radiography.

Obstructive pulmonary dysfunction: The presenting signs and symptoms of asbestos-related obstructive pulmonary dysfunction are indistinguishable from those of tobacco related COPD. Patients present with dyspnea, cough, and sputum production. Examination may reveal wheezing. Inspiratory rales suggest concomitant pulmonary fibrosis.

Lung Cancer: The presenting signs and symptoms of lung cancer that is due to asbestos exposure are indistinguishable from those of lung cancer that is due to other causes. Patients may present with cough, chest pain, hemoptysis, recurrent pneumonias, or weight loss, or they may be asymptomatic. Lung cancer related to asbestos exposure may be of any histologic subtype, though adenocarcinoma seems to be the most common.

Pleural disorders:

Pleuritis/Pleural effusion: Asbestos-related pleural effusions may be acute, sub-acute or chronic. The most common presenting symptom is dyspnea, with or without pleuritic pain. The effusion may also be asymptomatic, found incidentally on chest radiograph or on routine exam. Lung examination will reveal decreased breath sounds on the side of the effusion, and there may be a friction rub. An acute effusion may be exuberant with fever and pain. Chronic severe pleuritic pain is rare; vague discomfort is much more common. If persistent pain is present, the possibility of mesothelioma should be considered. Diagnosis is by exclusion of other causes of pleuritis.

Pleural fibrosis (localized pleural plaques or diffuse fibrosis): Pleural plaques are localized areas of pleural fibrosis. They are generally thought to be asymptomatic, but dyspnea can be present. Pleural plaques are usually diagnosed incidentally on chest radiograph. The most common presenting symptom for diffuse pleural thickening is dyspnea on exertion, which is usually mild. Chest pain is present in more than half of patients with diffuse pleural fibrosis; the pain is usually intermittent, but it may also be constant. Rapidly progressive or severe chest pain should raise the suspicion of pleuritis or mesothelioma. Lung examination may reveal decreased excursion of the thorax. The fibrosis may be unilateral or bilateral.

Mesothelioma: Mesothelioma is a malignancy involving the pleura of the lung. A pleural effusion often develops. Presenting symptoms include dyspnea and pleuritic chest pain, which may be severe and which is typically unrelenting and unilateral. Examination may reveal decreased breath sounds, indicating the presence of a pleural effusion.

The second requirement for the diagnosis of an asbestos-related pulmonary disorder is a history of exposure to asbestos, documented by occupational and/or environmental history or the presence of markers of exposure (e.g., pleural plaques or recovery of asbestos bodies). If the physician suspects that a patient has an asbestos-related pulmonary disorder, a thorough occupational and social history is essential to reveal and quantify any asbestos exposure. Since asbestos-related disorders can manifest many years after exposure, this history should include remote exposure fifteen years and more before presentation. History should also include sources of occupational exposure (both direct and "bystander"), environmental exposure, and passive exposure.

Occupations with risk of asbestos exposure include manufacture of products that contain asbestos, mining and milling of asbestos, construction trades (insulators, sheet metal workers electricians, plumbers, pipefitters, and carpenters), power plant workers, boilermakers, and shipyard workers. The patient's occupational title is not adequate--the physician must learn exactly what the patient's work involved. A history of possible "bystander exposure" is also important and is especially relevant in the construction trades, where the patients themselves may not have worked with asbestos but may have worked next to asbestos workers.

Environmental exposure includes living near asbestos mines and working or living in buildings with exposed sources of asbestos contamination. Passive exposure classically involves children who were exposed to asbestos brought into the home on the clothes of a parent who works with asbestos. Undisturbed and nonfriable asbestos insulation in buildings does not present a hazard.

The amount of exposure is also important. Both prolonged exposure over a period of 10-20 years and short, intense exposure can produce pathology. For example, shipyard workers who worked in confined spaces have developed asbestosis after only brief periods of heavy exposure. Similarly, insulation workers may have had intense short-term exposures; this type of exposure was common from WWII through the 1970s but is now rare.

Even a thorough history may not be fully informative. Patients may forget employment early in their lives and short periods of employment during which intense exposure. The characteristic radiographic signs of asbestos exposure (described in the section on imaging below) may be enough to document exposure in these cases.

Beware: there are other diseases that can mimic asbestos-related pulmonary disorders:

One of the criteria for diagnosis of asbestos-related pulmonary disorders is the exclusion of alternative plausible causes for the clinical findings. Diseases or conditions that can mimic the findings in asbestos-related pulmonary disorders include, but are not limited to:

other pneumoconioses (e.g., silicosis)

IPF/UIP

Hypersensitivity pneumonitis

sarcoidosis

obesity

COPD

lung cancer

tuberculosis

pneumonia

empyema

metastatic malignancy

Dressler's syndrome

trauma

collagen vascular diseases

Parenchymal Disorders

Asbestosis: When asbestosis is suspected, other (and perhaps treatable) causes of restrictive lung dysfunction or interstitial lung disease should be excluded, especially if an adequate exposure history is not evident.

The differential diagnosis of asbestosis includes other pneumoconioses, IPF/UIP, hypersensitivity pneumonitis, and sarcoidosis. Sometimes patients with another interstitial lung disease also have a history of asbestos exposure; patients may be exposed to more than one dust/fume in their occupations, so they may have combined disease. The restrictive dysfunction seen in pulmonary function testing in suspected cases of asbestosis can be due to obesity or to other interstitial lung diseases.

Asbestosis can be distinguished from other types of pulmonary fibrosis through a careful occupational history, examination of the clinical and radiographic presentation, and correlation with the pathologic findings, when necessary. Diagnostic uncertainty is most likely in patients with a history of heavy smoking and concurrent emphysema or with multiple occupational exposures. A history of asbestos exposure and the presence of pleural plaques are useful corollary evidence that the fibrosis may be asbestos-related. Rapid progression of disease suggests IPF or another etiology of fibrosis, rather than asbestosis.

Predominantly, upper lobe disease, hilar node enlargement and/or progressive massive fibrosis are generally not features of asbestosis; instead, they suggest other causes for the lung disease, such as silicosis. On biopsy, the presence of asbestos bodies should be sufficient to differentiate asbestosis from other forms of interstitial fibrosis. The chance of finding one asbestos body from background exposure alone is 1/1,000. Conversely, interstitial fibrosis without any asbestos bodies is most likely not asbestosis (although it cannot be totally excluded). Sometimes asbestosis is seen in conjunction with a second, unrelated interstitial lung disease (e.g., sarcoidosis) or in association with other pneumoconiosis (e.g., silicosis). In the absence of fibrosis, asbestos bodies are an indication of exposure, not disease.

Asbestomas: Occasionally, isolated fibrotic lesions associated with asbestos resemble solitary pulmonary nodules, which can be mistaken for lung cancers. These lesions usually occur against a background of irregular opacities. Lung biopsy is required to distinguish them from malignancy, especially since patients with asbestos exposure are at increased risk for lung cancer.

Obstructive lung disease: Asbestos-related obstructive lung disease is indistinguishable from smoking-related COPD on pulmonary function testing. Clues that the obstruction is due to asbestos exposure in a patient with a history of exposure include an absence of smoking history, concurrent pulmonary fibrosis, and pleural plaques.

Lung cancer: The differential diagnosis of asbestos-related lung cancer includes infection (especially mycobacterial), sarcoidosis, and asbestoma.

Pleural Disorders

Pleural effusion: When a pleural effusion is thought to be related to asbestos exposure, the differential diagnosis includes malignancy, especially mesothelioma or other thoracic malignancy, tuberculosis, and other infectious or inflammatory processes. Dressler's syndrome should be considered in patients who have had recent cardiac surgery.

Pleural plaques: Isolated pleural plaques may be associated with tuberculosis, trauma, hemothorax, or collagen vascular disease. Multiple or bilateral lesions that remain stable over time are almost invariably associated with asbestos exposure. Chest radiograph may reveal lesions that appear to be pleural plaques but that may be fat pads, parenchymal lesions, atelectatic streaks, visceral folds, or diaphragmatic straightening. CT scan can be useful in confirming the presence of plaques.

Diffuse pleural thickening: Other causes of acute pleuritis may lead to diffuse pleural thickening that can mimic asbestos-related pleural thickening. The most common causes include empyema and infected pleural effusion, tuberculosis, and trauma (including surgery), which may be remote events. These causes usually result in unilateral disease, as opposed to the bilateral disease seen in asbestos exposure. Occasionally, asbestos exposure results in apical pleural thickening, which can be difficult to distinguish from tuberculosis.

Mesothelioma: Diffuse pleural thickening or benign pleural effusions and mesothelioma need to be distinguished: Mesothelioma is more likely to be symptomatic at the time of detection and is more rapidly progressive; however, it may be difficult to differentiate among these disorders without a biopsy.

How and/or why did the patient develop asbestos-related pulmonary disorder (pathophysiology)?

Asbestos fibers are inhaled and deposited in the lungs, where they remain for long periods of time and also travel elsewhere in the body, causing inflammation, fibrosis, and sometimes malignant transformation. Asbestos consists of hair-like, long-fibered varieties of certain minerals. All types of asbestos are hydrated silicates, but they are chemically heterogeneous. The six minerals traditionally defined as asbestos are chrysotile, crocidolite, amosite, anthophyllite, actinolite and tremolite, but there are also some naturally occurring asbestiform amphiboles.

All types of asbestos appear to cause malignancy and inflammatory-fibrotic disorders, although the relative potency of the various types has been debated. Chrysotile fibers are likely the least toxic, as these fibers also split longitudinally, creating additional fibrils, which are more efficiently cleared from the lung than the amphibole asbestos fibers are.

Asbestos fibers are inhaled and deposited at airway bifurcations and in respiratory bronchioles and alveoli. Type 1 alveolar epithelial cells and macrophages take up the asbestos fibers. The activated macrophages can remove some fibers, but many remain. Some of those that remain become coated and are then called "asbestos bodies," which produce less cellular reaction; however, most fibers remain uncoated. Some fibers migrate to the pleura through direct penetration or are transported by macrophages along lymphatic channels to the pleura and throughout the body.

Asbestos has a prolonged residence in the body, and the fibers migrate induce inflammation and fibrosis wherever they migrate. The asbestos fibers induce apoptosis in macrophages and stimulate macrophages to produce mediators: oxygen radicals contribute to tissue injury, granulocytes are recruited, and they promote collagen synthesis and release additional mediators that contribute to tissue fibrosis by stimulating fibroblast proliferation and chemotaxis.

The results of these cellular reactions are various inflammatory processes. In the lung parenchyma, asbestos fibers induce alveolitis, inflammation in the surrounding interstitium, and inflammation followed by fibrotic change in the respiratory bronchioles and extending into the adjacent alveolar tissue. At the pleural service, the asbestos fibers cause pleural inflammation and fibrosis. Collagen deposits result in subpleural thickening, which may subsequently calcify. In the visceral pleura, such calcification may be associated with parenchymal fibrosis in adjacent subpleural alveoli, consistent with the pleural migration of asbestos fibers.

The chronic airway obstruction associated with asbestos exposure is likely multifactorial. A major site of asbestos deposits is in the walls of bronchioles. In the membranous bronchioles, these deposits lead to fibrosis and smooth muscle hyperplasia similar to that produced by cigarette smoking. In addition, work that leads to asbestos exposure is frequently associated with exposure to other agents that may affect the airways, and tobacco exposure may confound the picture.

The pathology seen in asbestos-related pulmonary disorders is related to the amount, duration, and latency of the exposure, as well as to the type of asbestos exposure. In asbestosis, the degree of fibrosis is clearly dose-dependent, with increases in the amount and duration of exposure leading to increased fibrosis. The major determinant of the presence of pleural thickening related to asbestos exposure is the duration, and possibly the dose, of the first exposure. Pleural thickening may occur after an episode of acute pleuritis, or it may be caused by extension of interstitial fibrosis into the visceral pleura. Pleural plaques, which generally occur at least twenty years after exposure, are related to the duration and amount of exposure. Asbestos-related pleural effusions do not seem to be related to the degree of exposure, and they can occur early or late.

Which individuals are at greatest risk of developing asbestos-related pulmonary disorders?

Asbestos exposure is necessary for the development of asbestos-related pulmonary disorders. Generally, the greater the exposure, the higher the risk of disease.

Asbestos has been used in many areas of industry. When asbestos fibers are bundled, the resulting material has high tensile strength, flexibility, and resistance to chemical and thermal degradation or electricity, making it a highly useful substance. Asbestos has been used extensively for insulation, brake linings, flooring, cement, paint, textiles, roofing, and other areas of industry. Commercial production and use of asbestos began in the late nineteenth century and steadily increased until the 1970s, when its hazards were first recognized. Commercial use has declined since then, and asbestos has been banned in many western countries. However, the material is still present in older buildings, and asbestos is still mined in some countries (e.g., Russia, China, and Canada). Most of the product is now used in Russia, Asia, and Africa. Figure 1 shows the risk of dying from asbestos-related pulmonary disorders based on occupation (Figure 1).

Figure 1.

Proportionate Mortality Ratio for Asbestos-related pulmonary disorders based on Occupation

Despite its decreased use, since asbestos-related diseases take years to develop, we continue to see these diseases throughout the world. In addition, environmental exposure to asbestos can be seen in areas near naturally occurring deposits of asbestiform fibers. For example, in Libby, Montana, a tremolite-like asbestiform mineral is found in association with vermiclite. Some areas in Turkey also have very high levels of environmental asbestos exposure.

Occupational exposure to asbestos is highly associated with pathology. Studies have found that over 80 percent of asbestos workers have an abnormal CXR, and pleural plaques are present in up to 70 percent by thirty years after exposure. Widespread use of asbestos in the past is reflected in the finding that pleural plaques (a marker of exposure to asbestos) are present on the chest films of 2.3 percent of US males.

The populations most at risk fall into four categories:

1) older patients who were in high-risk occupations and who had had high levels of asbestos exposure, such as textile, construction or shipyard workers, plumbers, mechanics, miners, and factory workers. Their families may have had passive exposure when workers carried asbestos home on their clothing.

2) Workers in occupations that involved the management of the remaining asbestos hazard, such as building and facility maintenance, asbestos-abatement operations, and the renovation and demolition of structures containing asbestos.

3) In the developing world, workers and their families continue to be exposed to asbestos. In some former Eastern bloc nations and rapidly industrializing countries in Asia, the use of asbestos may even be increasing.

4) Environmental exposure to asbestos can occur in certain geographic areas. Exposure to large amounts of dust containing asbestos can occur during catastrophic events like the World Trade Center collapse in New York City in 2001. Different types of asbestos carry different risks; of the two main types of asbestos, chrysotile (serpentine) and amphibole (mostly amosite and crocidolite), chrysotile, because of its physical characteristics, likely carries less risk than the amphiboles.

Cigarette smoking in combination with asbestos exposure increases the risk of developing some asbestos-related disorders. Asbestosis is more prevalent and more advanced for a given duration of exposure in cigarette smokers than in non-smokers, perhaps because the effect of cigarette smoke on ciliary function leads to decreased clearance of asbestos fibers in the lung. Both smokers and ex-smokers with asbestos exposure have a higher incidence of asbestos-related irregular opacities on their chest radiographs than do non-smoking asbestos-exposed workers. The risk for lung cancer is also increased in smokers exposed to asbestos, and the effects are multiplicative, not additive. Smoking likely does not affect the presentation of asbestos-related pleural fibrosis, pleural plaques, or mesothelioma.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

Not applicable.

What imaging studies will be helpful in the diagnosis of asbestos-related pulmonary disorders?

Chest radiographs (CXR) and high-resolution computed tomography (CT) are the primary imaging studies to use in evaluating for asbestos-related pulmonary disorders. Ultrasound, magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT can also be useful in specific instances.

Parenchymal disorders: The chest radiograph has long been the basis for assessing asbestos-related disease of both the lung and the pleura. The initial presentation of asbestosis on chest radiograph is typically bilateral, small, primarily irregular, parenchymal opacities in the lower lobes (Figure 2). Over time, the distribution and density or "profusion" of opacities may spread.

Figure 2.

Chest Radiograph showing basilar interstitial opacities consistent with asbestosis. Credit: WN Rom, MD, NYU School of Medicine

A standardized system, the International Classification of Radiographs of Pneumoconiosis, or ILO (International Labour Organization) classification, was developed in the 1950s and, with some revisions (the last in 2000), is still used today. The ILO classification is based on a PA chest film, where each film is given a "profusion" score based on the presence of parenchymal opacities. The classification of the films is as follows: 0/0 indicates a film without evidence of fibrosis, 0/1 indicates a film suggestive of but not diagnostic of fibrosis, 1/0 indicates a film that is presumed diagnostic but is not unequivocal, and 1/1 indicates a film that is diagnostic of fibrosis. People trained in the system are called "B-readers."

Some compensation systems may require that the X-ray be classified by the ILO system once it has been established that a patient has been exposed to asbestos. The ILO classification profusion score correlates strongly with mortality risk, reduced diffusing capacity, and diminished ventilatory capacity in asbestosis. A chest film that clearly shows the characteristic signs of asbestosis in the presence of a compatible history of exposure is adequate for the diagnosis of the disease. However, the chest x-ray has limited sensitivity and specificity in cases of mild or early asbestosis. Chronic airway obstruction that is due to asbestos exposure will appear on CXR and CT as hyperinflation, and emphysematous changes may be present.

Chest CT, especially high-resolution chest CT (HRCT, 2cm intervals or less) is much superior to chest films in identifying parenchymal fibrosis and atalectasis. HRCT should be used when the plain film is equivocal or normal when asbestos-related pulmonary disease is suspected because of symptoms, abnormal PFTs, and exposure history. Possible CT findings in asbestosis include honeycombing, ground-glass opacities, septal and interlobular fissure thickening, subpleural opacities or lines, diffuse pleural thickening, parenchymal bands, rounded atalectasis, and pleural plaques. Findings are typically bilateral (Figure 3).

Figure 3.

Portion of chest CT showing asbestosis in basilar region of lung. Credit: WN Rom, MD, NYU School of Medicine

HRCT can also help exclude other conditions that may be causing the symptoms or CXR findings, such as emphysema, bronchiectasis, and vessel prominence. Prone views can help distinguish between dependent atalectasis and parenchymal fibrosis in the posterior lung fields. Interlobar pleural thickening may mimic lung nodules on CT scan. Asbestosis is characteristically most advanced and appears earliest in the lower lung fields. Rarely, there is a syndrome of massive bilateral upper lobe fibrosis in the absence of tuberculosis, lung cancer or other occupational exposures. HRCT findings may be present before clinical disease and may correlate with pulmonary function tests. Positron emission tomography (PET)/CT may be helpful in distinguishing nodular lesions that are due to fibrosis from those that are due to malignancy, and for staging of lung cancer.

Pleural disorders: Chest radiographs and CT scans are also useful in diagnosing pleural disorders related to asbestos exposure. Pleural plaques are often seen on plain films ( Figure 4). Plaques are usually bilateral but not symmetric, they appear in the lower posterior parietal pleura or over the diaphragm, they have sharp borders with irregular margins, and they may or may not appear calcified on the CXR. The CXR is sensitive, although it may misidentify abnormalities that resemble plaques, such as fat pads and parenchymal lesions.

Figure 4.

Chest radiograph showing asbestosis, pleural plaques and COPD. Credit: WN Rom, MD, NYU School of Medicine

Pleural thickening is difficult to pick up on CXR. The first and sometimes only sign may be obliteration of the costophrenic angle, which is involved in 90 percent of cases of pleural thickening. Over time, calcification of the pleura occurs that may involve fissures, leading to prominence of the fissures on CXR. The thickening may be unilateral or bilateral. When pleural thickening is seen, it is often associated with fibrous strands (crow's feet) extending into the parenchyma and may be present along with pleural plaques. A rare variant is progressive apical thickening associated with fibrosis of the upper lobe. Pleural effusions that are due to asbestos-related pleuritis can be seen on CXR and may be unilateral or bilateral.

Chest CT is more accurate in identifying early pleural thickening than plain films are, and it can distinguish between pleural thickening or plaques and extrapleural fat. The pleural thickening on CT may be patchy or diffuse and may be unilateral or bilateral (Figure 5).

Figure 5.

Chest CT showing pleural plaques. Credit: William N. Rom, MD

Other pleural findings may be seen on CXR and CT in asbestos-related pulmonary disorders. Rounded atalectasis, which appears as a mass on CXR or CT and is thought to develop from infolding of thickened visceral pleura and collapse of the intervening lung parenchyma, is more common after asbestos exposure than are other causes of pleuritis. The "comet sign," which is more easily seen on HRCT, is pathognomonic: a band connects the mass to an area of thickened pleura. Rounded atalectasis remains stable or changes minimally over time. It may appear suddenly after an episode of pleuritis and may be bilateral or multiple.

Other imaging modalities may be helpful in individual cases. Ultrasound may be useful in locating pleural fluid. Magnetic resonance imaging (MRI) can be of value in identifying rounded atelectasis and distinguishing pleural lesions from fluid accumulation. Positron Emission Tomography (PET)/CT scans can sometimes help differentiate benign from malignant effusions. These scans also used for staging mesothelioma and lung cancer. Gallium scanning may rarely be used to evaluate extensive pleural fibrosis with active inflammation, a syndrome called pacypleuritis, or malignant effusions that are due to lung cancer or mesothelioma.

What non-invasive pulmonary diagnostic studies will be helpful in the diagnosis of asbestos-related pulmonary disorders?

Pulmonary function testing with lung volumes and diffusing capacity is important in the evaluation for asbestos-related pulmonary disorders.

Patients with asbestos-related pulmonary disorders may have obstructive or restrictive dysfunction or a combination of the two. The restrictive impairment may be due to interstitial disease, pleural disease, or both. Carbon monoxide diffusing capacity is commonly reduced because of decreased alveolar-capillary gas diffusion and ventilation-perfusion mismatching. Obstructive dysfunction may be due to asbestos-induced small-airway disease and/or concomitant COPD. Since both obstructive and restrictive dysfunction may be present, complete pulmonary function testing, including lung volumes and diffusing capacity, should be performed in asbestos-exposed individuals.

Additional testing may include room-air blood gases to determine gradient and exercise testing, especially if the degree of dyspnea correlates poorly with the PFT measurements. COPD that is due to cigarette smoking may complicate the recognition of asbestos-related lung disease: the TLC may be normal when both disorders are present because of a restrictive process that offsets air trapping. Similarly, chronic obstructive dysfunction that is due to asbestos may be missed if restrictive dysfunction is also present.

Parenchymal disorders: In pure asbestosis, the classic finding is restrictive impairment with decreased diffusing capacity. Mixed restrictive and obstructive impairment is also frequently seen, but isolated obstructive impairment is unusual. The restrictive dysfunction is primarily a decrease in FVC and total lung capacity, with decreased diffusing capacity and eventually arterial hypoxemia. Large-airway function (FEV1/FVC ratio) is generally well preserved, with obstructive dysfunction manifesting as increased resistance at low lung volumes. The decreased diffusing capacity may be the most sensitive indicator of early asbestosis, but it is also a non-specific finding and may be seen in many other conditions.

Large-airway obstructive dysfunction with a reduction in the FEV1/FVC ratio is also seen in both smoking and non-smoking asbestos-exposed individuals. The progression is thought to begin in the small airways, consistent with bronchiolitis--an early finding in asbestosis--and progress to the larger airways.

Pleural disorders: Isolated pleural disease related to asbestos exposure also results in restrictive pulmonary dysfunction. Pleural plaques are generally thought to be asymptomatic, but dyspnea can be present, and pulmonary function testing frequently confirms a significant reduction in lung function. The decline tends to be worse with circumferential plaques, but it may be present with isolated plaques as well. Both lung volumes and diffusing capacity may be decreased even when fibrosis is not apparent; the decreased diffusing capacity may be related to early subclinical fibrosis. Diffuse pleural thickening has an even more significant impact on pulmonary function. The classic finding is a decrease in FVC with preservation of diffusing capacity--an entrapped lung pattern. Of course, if asbestosis is present as well, the diffusing capacity may also be decreased.

What diagnostic procedures will be helpful in the diagnosis of asbestos-related pulmonary disorders?

Diagnostic procedures that may be helpful in diagnosing and evaluating asbestos-related pulmonary disorders include:

Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBX)

Thoracentesis

Thoracoscopy and pleural biopsy

Open-lung biopsy

As discussed above, the diagnosis of asbestos-related lung disorders can sometimes be made on the basis of history, clinical symptoms, and imaging. However, additional testing is often required to confirm the diagnosis and rule out other possible etiologies. Bronchoscopy with BAL can confirm the presence of asbestos bodies, indicating asbestos exposure in the past. Open-lung biopsy may be required for definitive diagnosis of parenchymal asbestos-related disorders, whereas thoracentesis or thoracoscopy and pleural biopsy may be needed for pleural asbestos-related disorders.

When imaging suggests a pulmonary disorder consistent with asbestos-related lung disease, bronchoscopy with bronchoalveolar lavage (BAL) can often provide evidence of asbestos exposure. Asbestos fibers and their derivatives, asbestos bodies (see definition in pathology section, below) can be identified and quantified in lung tissue and BAL. The asbestos fibers are difficult to see using light microscopy--the pathologist will need to use scanning/transmission electron microscopy. Asbestos bodies are larger than asbestos fibers and can be seen using light microscopy alone.

Asbestos bodies in the BAL fluid correlate with asbestos bodies in the lung and reflect occupational exposure. The number of asbestos bodies seen in BAL fluid also correlates with the presence of asbestos-related pulmonary disorders. Patients with asbestosis have more asbestos bodies on BAL than do those with mesothelioma or asbestos-related lung cancer, but those with mesothelioma or asbestos-related lung cancer have more asbestos bodies than do patients with only pleural plaques.

The type of asbestos exposure can also sometimes be identified by analyzing the BAL fluid with energy-dispersive x-rays to detect the magnesium and silicon characteristic of most forms of asbestos, whereas a large iron peak signifies an amphibole (except tremolite). Such identification may provide information about the type, intensity, duration, and latency of exposure. However, because some fibers, especially chrysotile, dissolve over time, the absence of a high fiber count does not necessarily mean there has been no exposure.

Sputum analyses and transbronchial biopsies to look for asbestos bodies are not sensitive in assessing asbestos exposure.

Parenchymal disorders: When the diagnosis of asbestosis is in doubt, an open-lung biopsy may be necessary to obtain tissue for pathology. Only severe grades of asbestosis are detectable by gross examination or palpation, so biopsies should include peripheral and central areas of the lung, along with any areas that are visibly diseased. If open-lung biopsy is not an option, the BAL cells can also be digested with bleach, and the residue can then be analyzed for asbestos fibers by electron microscopy. The appearance of fibers or beaded fibers on a single centrifuged BAL sample mounted on a diff-quick slide is an indicator of parenchymal asbestosis.

Pleural disorders: When asbestos-related pleural disease is suspected, thoracentesis and/or pleural biopsies may be necessary. In asbestos-related pleuritis, the pleural effusion is exudative and may be hemorrhagic, with variable numbers of erythrocytes, neutrophils, lymphocytes, mesothelial cells, and (often) eosinophils. Pleural fluid cytology may diagnose alternative causes of effusion but is unlikely to diagnose mesothelioma. In fact, a non-specific effusion often precedes the diagnosis of mesothelioma by several years. However, if an asbestos-related effusion is present for more than three years with little or no change, it is generally considered to be a benign pleuritis.

If no alternative diagnosis is made from the thoracentesis, thoracoscopy with or without pleural biopsy can provide a definitive diagnosis. Thoracoscopy can reveal pleural plaques, especially on the posterior parietal pleura and over the diaphragm. Plaques are raised and sharply circumscribed with a smooth or rounded knobby surface, and they range in color from white to pale yellow. The plaques generally spare the costophrenic angles and the apices. In contrast, diffuse pleural thickening affects the visceral pleural surface. Pale gray diffuse thickening blends at the edges with the more normal pleura, and the thickness varies from less than 1mm to more than 1cm. Adhesions to the parietal pleural are common.

Thoracoscopy can also identify lesions consistent with mesothelioma, and biopsies can be performed under direct visualization. Blind pleural biopsy is not likely to be diagnostic in asbestos-related pleural disease.

What pathology/cytology/genetic studies will be helpful in the diagnosis of asbestos-related pulmonary disorders?

As noted above, if the clinical history and imaging suggest an asbestos-related pulmonary disorder, the finding of asbestos fibers or asbestos bodies in the lung may be sufficient in some cases to confirm the diagnosis if no other etiology is found. Asbestos bodies are asbestos fibers that have been coated with an iron-rich, proteinaceous concretion. Other fibers in the lung can also become coated in this way (called ferruginous bodies), but more than 90 percent of all coated fibers have asbestos cores.

Asbestos bodies usually form after exposure to amphibole asbestos since this type of asbestos is more persistent in lung tissue than chrysotile asbestos is. The asbestos bodies can be seen and quantified by light microscopy, and an iron stain may help to identify them (Figure 7) (Figure 8). Levels of at least one asbestos body per field of a tissue section on a slide under light microscopy are consistent with occupational exposure.

Figure 6.

Asbestos body. Credit: WN Rom, MD, NYU School of Medicine

Figure 7.

Asbestos body. Credit: WN Rom, MD, NYU School of Medicine

Figure 8.

Chest radiograph showing pleural plaques and COPD. Credit: WN Rom, MD, NYU School of Medicine

TBBX is a less reliable source with which to look for the asbestos bodies. Asbestos bodies and fibers can be identified and quantified in BAL specimens, and the count of asbestos bodies in BAL seems to correlate with the presence or degree of fibrosis. However, the presence of asbestos bodies alone, in the absence of typical clinical and radiographic findings, is not sufficient to establish the diagnosis of asbestosis.

Parenchymal disorders:Asbestosis is associated with a variable degree of chronic inflammation and increased numbers of alveolar macrophages, including multinucleate giant cells. BAL generally shows a modest increase in neutrophils. The amount of neutrophilia correlates with crackles on physical exam, degree of hypoxia, and severity of disease. Abnormalities in BAL may even be present before the onset of clinical disease.

An open-lung biopsy may be necessary for a definitive diagnosis of asbestosis. The College of American Pathologists has developed histologic criteria for asbestosis and a grading system to describe the severity and extent: Grade I, the mildest level of severity, involves the alveolated walls of respiratory bronchioles and the alveolar ducts. Grade II involves greater proportions of the acinus. In Grade III, the whole acinar structure is involved, and some alveoli are completely obliterated. In Grade IV, alveolar collapse with fibrosis and honeycomb remodeling result in new dilated spaces in the parenchyma. These patterns of acinar fibrosis, together with the demonstration of asbestos bodies, are diagnostic of asbestosis.

Chronic airway obstruction that is due to asbestos exposure has a histologic appearance similar to that of the obstructive disease caused by cigarette smoking. Both inflammation and airway fibrosis is seen, and there is fibrosis and smooth muscle hyperplasia in the membranous bronchioles. However, in contrast to the changes seen in cigarette smokers, the respiratory bronchioles in asbestos-related obstructive disease show fibrosis extending into the alveolated portions of the walls and the alveolar duct. Asbestos bodies may also be seen in the walls of the respiratory bronchioles. These lesions may be true asbestosis or may represent a distal small-airway disease caused by asbestos exposure.

Pleural disease: Pleural disease related to asbestos exposure can be biopsied thoracoscopically. Pleural plaques are often diagnosed by imaging alone. When thoracoscopic biopsy is performed, the pathology seen is mature collagen fibers arranged in an open basket-weave pattern, covered by flattened or cuboidal mesothelial cells. The lesion is sharply demarcated and is relatively avascular and acellular, with minimal inflammation and often with central calcification. The histologic appearance of diffuse pleural fibrosis is immature granulation tissue and fibrin at the surface, progressing to mature collagen adjacent to the lung. The fibrosis may extend a few millimeters into the lung parenchyma and into the lobular septae.

If the physician decides the patient has an asbestos-related pulmonary disorder, how should the patient be managed?

No intervention has proven to alter the subsequent evolution of asbestos-related pulmonary disorder. Management should be focused on avoidance of further exposures symptomatic treatment, supportive care, and monitoring for malignancy. Patients should be informed that they have disease that is work-related and that they may have legal options for compensation.

Parenchymal Disorders: Patients diagnosed with asbestosis or asbestos-related obstructive lung disease are considered at risk of progressive lung disease and malignancy and should absolutely avoid further exposure to asbestos or other occupational environmental exposures. Patients should be monitored for progression with annual CXR and full PFTs with exercise oximetry if indicated. Supplemental oxygen should be prescribed if oxygen saturation begins to decline. Corticosteroids, and other medications that are used for other types of pulmonary fibrosis have not been shown to be of benefit in asbestosis.

Physicians should ensure that patients receive all appropriate immunizations, including the pneumococcal pneumonia and annual influenza vaccines. Any comorbid diseases should be diagnosed and treated, especially those affecting pulmonary function, such as COPD and asthma. Chest CTs to screen for lung cancer may be indicated (see below). The treatment of lung cancer is covered in a separate chapter.

Pleural Disorders: Patients with diffuse pleural fibrosis and restrictive dysfunction may sometimes benefit from decortication. When the only manifestation of asbestos exposure is pleural plaques, no treatment necessary. However, as above, medical surveillance is recommended. The treatment of mesothelioma is covered in a separate chapter.

Regardless of whether a clinical asbestos-related pulmonary disorder is diagnosed, a history of significant asbestos exposure obligates the physician to take certain steps to evaluate for current disease/impairment and to assess future risk of disease.

1. Education. Patients who have documented or plausible exposure histories should be educated about the associated diseases, exposure-response relationships for the diseases, latency periods, and the future risk of malignancy. Education about other risk factors for respiratory illness, especially smoking and occupational exposures, should be provided. Reassurance can often be offered, as the public perception of risk is much higher than the actual risk.

2. Baseline evaluation: Baseline evaluation for patients who have had significant asbestos exposure should include CXR and PFTs with diffusing capacity. Physicians should consider a low-dose CT scan to evaluate for lung cancer if the patient has a history of cigarette smoking and is older than age fifty, especially in light of recent data from the National Lung Cancer Screening Trial (NLST) on the efficacy of CT scan screening for lung cancer in smokers age fifty-five and older. If a CT scan is performed, it should include high-resolution images to evaluate for asbestosis.

3. Monitoring: If the baseline evaluation is not suggestive of asbestos-related disease, monitoring should be considered. OSHA requires monitoring only during employment in jobs with the risk of asbestos exposure. However, this requirement does not take into account the latency of disease.

Monitoring for patients with a history of exposure, who have no disease, and who are at least ten years after exposure should include a CXR and PFTs every 3-5 years. As mentioned above, physicians should consider low-dose CT screening as well. However, the data in support of this approach is evolving, and it is unclear how frequently and for how long CT screening should continue. The risk of other malignancies is increased, but routine screening beyond that recommended for the general population is not currently recommended.

4. Avoidance: No prophylactic medication or treatment is available to prevent the development of asbestos-related pulmonary disorders. Individuals should avoid further exposure to asbestos and exposure to other carcinogens or pulmonary irritants, especially cigarette smoking.

What is the prognosis for patients with asbestos-related pulmonary disorders managed in the recommended ways?

There is no effective treatment for asbestos-related pulmonary disorders. Asbestos-related pulmonary disorders generally occur after a significant latency period after exposure, and the prognosis varies depending on the disorder that develops.

Parenchymal disorders: The latency period for asbestosis is determined by the duration and intensity of the exposure, but it can range from ten to thirty years after exposure. At current conditions in the United States, the latency period is likely to be two decades or more, but if a high level of exposure occurs, asbestosis can occur much more quickly. The earliest clinical finding in asbestosis is dyspnea and restrictive dysfunction on pulmonary function testing, with decreased lung volumes and diffusing capacity. Over time, asbestosis may remain static or progress, with studies showing an average decrease in vital capacity of 18 percent over ten years; pathologic and radiologic abnormalities progress similarly.

Regression of disease is very unusual and may indicate a misdiagnosis. Progression of asbestosis is usually slower than in IPF, but it follows a similar pattern with worsening pulmonary function and dyspnea, which may progress to cor pulmonale, secondary polycythemia, respiratory insufficiency and failure. The factors that determine prognosis are poorly defined. Progression, which is more common in persons who already have radiographic abnormalities, is associated with the level and duration of exposure so it likely relates to cumulative exposure.

Chronic airway obstruction from asbestos exposure follows a similar pattern to that of COPD from cigarette smoking: there is an accelerated decline in airflow over time, with or without continued asbestos exposure. When combined with the other effects of asbestos or with other pulmonary conditions like emphysema, there may be significant and progressive decline in lung function.

Pleural disorders: Asbestos-related pleuritis may occur early (within ten years of exposure) or late. The pleuritis may be unilateral or bilateral, may present acutely with fever and pain, may be asymptomatic, and may persist for months. The condition can also recur on the same or the opposite side. Traces of the effusion may be observed years later as a blunted costophrenic angle or as diffuse pleural thickening. Acute pleuritis may underlie many subsequent cases of diffuse pleural thickening that may occur many years later. Diffuse pleural fibrosis can progress, leading to ventilatory failure with carbon dioxide retention, cor pulmonale, and death, even without parenchymal fibrosis. Progression of pleural fibrosis seems to level off about fifteen years after onset.

Pleural plaques are correlated with parenchymal disease. However, pleural plaques can be present without parenchymal disease and vice versa. Slow progression of plaques is typical, but the plaques remain generally asymptomatic. Although plaques do not progress to malignant mesothelioma, the presence of plaques is associated with a greater risk of asbestosis, mesothelioma, and lung cancer when compared with the risk to subjects with comparable asbestos exposure and no plaques. This increased risk is thought to be due to greater exposure or retained body burden, not to malignant transformation of the plaques. Plaques can be seen as a marker for elevated risk of asbestosis or malignancy, and patients should be monitored closely. The number and extent of pleural plaques is associated with a decline in pulmonary function (FVC).

There is a strong association between the presence of benign asbestos-related pulmonary disease and the risk of malignancy. However, most patients with benign asbestos-related disease do not develop cancer, and cancer risk is increased in people exposed to asbestos, even if they do not have signs of benign disease.

Table 1

Asbestosis Grading System
0 No fibrosis associated with bronchioles.
I Fibrosis involves the alveolated walls of respiratory bronchioles and the alveolar ducts but is not present in more distant alveoli.
II Fibrosis involves greater proportions of the acinus, but normal lung still remains in a zone between adjacent bronchioles.
III The whole acinar structure is involved with fibrosis, and some alveoli are completely obliterated.
IV Alveolar collapse with fibrosis and honeycomb remodeling results in new dilated spaces in the parenchyma.

What’s the evidence?

"Diagnosis and initial management of nonmalignant diseases related to asbestosis: the official statement of the American Thoracic Society". Am J Respir Crit Care Med. vol. 170. 2004. pp. 691-715.

Comprehensive review of non-malignant asbestos-related pulmonary diseases.

http://www.osha.gov/sltc/asbestos.

Has data on OSHA requirements for workplace safety and current statistics of asbestos-related diseases.

Rom, WN. "Asbestos-related diseases". Environmental and occupational medicine. Lippincott-Raven. 1998. pp. 349-375.

A comprehensive description of the spectrum of asbestos-related pulmonary disorders

Rom, WN, Travis, WD, Brody, AR. "Cellular and molecular basis of the asbestos-related diseases [State of the Art]". Am Rev Respir Dis. vol. 143. 1991. pp. 408-422.

A comprehensive review of the biology underlying asbestos-related pulmonary disorders.

Hughes, JM, Weill, H. "Asbestosis as a precursor of asbestos related lung cancer: results of a prospective mortality study". Br J Ind Med. vol. 48. 1991. pp. 229-33.

This prospective study of more than 800 workers involved in manufacturing of asbestos cement products demonstrates that only those workers with radiographic evidence of asbestosis experienced an excessive risk of developing lung cancer.

Berry, G, Newhouse, ML, Antonis, P. "Combined effect of asbestos and smoking on mortality from lung cancer and mesothelioma in factory workers". J Ind Med 1985. vol. 42. Jan. pp. 12-8.

This retrospective study of over 1600 workers in an asbestos factory showing that the risk of mesothelioma is independent of smoking history.

Nicholson, WJ, Perkel, G, Selikoff, IJ. "Occupational exposure to asbestos: population at risk and projected mortality--1980-2030". Am J. Ind. Med. vol. 3. 1982. pp. 259-311.

Projected morbidity/mortality in the coming years.

Becklake, MR, Bagatin, E, Neder, JA. "Asbestos-related diseases of the lungs and pleura: uses, trends and management over the last century". Int J Tuberc Lung Dis. vol. 11. pp. 356-369.

Review.

Mossman, BT, Ge, JB. "Asbestos-related diseases". N Engl J Med. vol. 320. 1989. pp. 1721.

Review.

Paris, C, Thierry, S, Brochard, P. "Pleural plaques and asbestosis: dose-and time-response relationships based on HRCT data". Eur Respir J. vol. 34. 2009. pp. 72.

Study of pleural plaques and asbestosis in relation to exposure--using HRCT.

Kilburn, KH, Warshaw, RH. "Airways obstruction from asbestos exposure: effects of asbestosis and smoking". Chest. vol. 106. 1994. pp. 1061.

Combined affect of asbestos and tobacco exposure on airway obstruction.

Larson, TC, Meyer, CA, Kapil, V. "Workers with Libby amphibole exposure: retrospective identification and progression of radiographic changes". Radiology. vol. 255. 2010. pp. 924.

Study of workers in Libby Montana.

Aberle, DR, Gamsu, G, Ray, CS. "High-resolution CT of benign asbestos-related diseases: clinical and radiographic correlation". AJR Am J Roentgenol. vol. 151. 1988. pp. 883.

HRCT findings in asbestos exposure.

Karjalainen, A, Piipari, R, Mantyla, T. "Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma". Eur Respir J. vol. 9. 1996. pp. 1000.

Significance of asbestos bodies in BAL fluid.

Sabastien, P, Armstrong, B, Monchaux, G, Bignon, J. "Asbestos bodies in bronchoalveolar lavage fluid and in lung parenchyma". Am Rev Respir Dis. vol. 137. 1988. pp. 75.

Schwarz, DA, Davis, CS, Merchant, JA. "Longitudinal changes in lung function among asbestos-exposed workers". Am J Respir Crit Care Med. vol. 150. 1994. pp. 1243.

Asbestos effects on lung function.

Rom, WN. "Accelerated loss of lung function and alveolitis in a longitudinal study of non-smoking individuals with occupational exposure to asbestos". Am J Ind Med. vol. 21. 1992. pp. 835-844.

Study specifically in non-smokers demonstrates loss of lung function due to asbestos exposure.
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