Pleural Diseases

Four forms of pleural disease related to asbestos exposure have been described: pleural plaques, benign asbestos pleural effusions, pleural fibrosis, and malignant mesotheliomas.

Pleural plaques are the most common manifestation of asbestos exposure. They are smooth, white, raised, irregular lesions found on the parietal pleura, commonly located in the lateral and posterior midzones and over the diaphragms (Fig. 1). They are commonly asymptomatic and are recognized only on chest imaging. Macroscopic calcification is common. Plaques are not associated with the development of a malignant mesothelioma. They are, however, markers of asbestos exposure, and thus persons with pleural plaques are at risk for developing pulmonary fibrosis, mesothelioma, and lung cancer.

Figure 1 Computed tomography of the chest demonstrating pleural plaques (arrows) resulting from asbestos exposure.

(Courtesy of Dr. Omar Lababede.)

Benign asbestos pleural effusions may be silent or can manifest with pain, fever, and shortness of breath. They are an early manifestation of asbestos exposure, occurring within 15 years of the initial exposure. The diagnosis of this condition is one of exclusion. It requires known asbestos exposure; an exudative, bloodstained, lymphocyte-predominant effusion; lack of tumor development over a 3-year follow-up; and no evidence of another cause of the effusion. Often a thoracoscopy with biopsy is performed to exclude other causes. A benign asbestos pleural effusion is usually transient but requires close follow-up. It is not associated with the development of a malignant mesothelioma.

Pleural fibrosis typically occurs in persons who have had a remote exposure to asbestos (>20 years before) that was short lived and heavy in intensity. It can occur as a focal or diffuse process. The fibrosed pleura can surround the lung, leading to a trapped lung, or can fold in on itself, encasing a portion of the parenchyma. The masslike lesion that results is known as rounded atelectasis. All forms of pleural fibrosis are difficult to distinguish from malignancy, and they usually require biopsies to ensure benignity. The presence of pleural fibrosis indicates an increased risk of pulmonary fibrosis.

Asbestos exposure is responsible for most cases of malignant mesothelioma. The presentation is typically the insidious onset of nonpleuritic chest wall pain 20 to 40 years after the initial exposure. The pain can radiate to the upper abdomen or shoulder and is often associated with dyspnea and systemic symptoms. The mass typically involves both the parietal and visceral pleura. Local invasion is common, with symptoms stemming from the organs invaded. Chest imaging typically reveals an effusion ipsilateral to the pleural disease and might show pleural plaques in the contralateral hemithorax. Open biopsy is required for the diagnosis. Treatment options are unsatisfactory. There is no synergy between smoking and asbestos exposure for the development of a malignant mesothelioma.

Asbestosis

The term asbestosis refers to pulmonary fibrosis secondary to asbestos exposure. Risk factors for the development of asbestosis include increased levels and duration of exposure, younger age at initial exposure, and exposure to the amphibole fiber type. It is not associated with smoking.

Common symptoms include progressive shortness of breath and a nonproductive cough. Chest pain may be reported. On examination, inspiratory crackles on lung auscultation and digital clubbing are present with varying frequency.

The parenchymal fibrotic changes are most prominent in the lower lobes and subpleural areas. Pulmonary function testing reveals restrictive lung disease with a decreased diffusing capacity for carbon monoxide. Thus, radiographic and physiologic testing findings can be indistinguishable from those of other causes of pulmonary fibrosis. The presence of concomitant pleural disease and the finding of asbestos or ferruginous bodies (Fig. 2) in pathologic samples help to support the diagnosis.

Figure 2 Pleural disease concomitant with asbestos or ferruginous bodies in pathologic samples.

A, Asbestos ferruginous bodies (arrows) (hematoxylin and eosin ×100). B, Ferruginous body (hematoxylin and eosin ×250).

(Courtesy of Dr. Carol Farver.)

Asbestosis can appear and progress long after exposure has ceased. It can remain static or can progress over time. There is no known effective therapy. The number of reported deaths from asbestosis has increased over time, related to the use of asbestos in a time-delayed manner (Fig. 3).

Figure 3 The number of deaths from asbestosis has increased through the years, related to asbestos use in a time-delayed fashion.

(From National Institute for Occupational Safety and Health (NIOSH): Work-Related Lung Disease Surveillance Report, 1999, publication no. 2003-111. Morgantown, WV, Division of Respiratory Disease Studies, NIOSH, 2000.)

Asbestos as a Carcinogen

Asbestos is a known carcinogen. The risk of developing lung cancer in a person exposed to asbestos is enhanced in a multiplicative fashion by concomitant cigarette smoking. Lung cancer more commonly occurs in persons who also have asbestosis. All cell types are associated with exposure. The lag time to the development of lung cancer is usually more than 20 years. Treatment follows the principles of lung cancer therapy in persons without prior asbestos exposure. Comorbid lung disease can limit the treatment options.

Silicosis

Inhalation of crystalline silica can lead to a fibronodular parenchymal lung disease known as silicosis. This most commonly occurs in a form known as chronic or simple silicosis. Persons with chronic silicosis typically have had more than 20 years of silica exposure. They are usually without symptoms, although shortness of breath and cough can develop. Their disease is thus recognized radiographically with multiple small nodules with an upper lobe predominance (Fig. 4). Hilar adenopathy with eggshell calcification can be seen. Pulmonary function abnormalities do not invariably occur. Pathologically, the nodules are recognized as silicotic nodules.

Figure 4 This chest radiograph shows the multiple small nodules (arrows) with upper lobe predominance characteristics.

(Courtesy of Dr. Omar Lababede.)

The pulmonary nodules seen with chronic silicosis can progressively conglomerate and be accompanied by fibrosis, a state that has been termed conglomerate silicosis and progressive massive fibrosis. Shortness of breath and cough can become debilitating. Pulmonary function testing often shows a mixed obstructive and restrictive defect, with a reduction in the diffusing capacity. Death due to silicosis continues to occur (Fig. 5).

Figure 5 The number of deaths and death rates from silicosis have declined but not disappeared over time.

(From National Institute for Occupational Safety and Health (NIOSH): Work-Related Lung Disease Surveillance Report, 1999, publication no. 2003-111. Morgantown, WV, Division of Respiratory Disease Studies, NIOSH, 2000.)

Acute and accelerated forms of silicosis are more rapidly progressive, typically associated with intense exposure to silica. Acute silicosis can develop within months of exposure and resembles acute airspace disease on radiographs. Pathology mimics alveolar proteinosis, with proteinaceous material in the alveoli, but interstitial involvement and early nodule formation can be seen. Rapid progression to acute respiratory failure is common. Accelerated silicosis occurs after 5 to 15 years of exposure. Patients are usually symptomatic and often progress to respiratory failure and death. They are recognized by the development of upper zone nodules and fibrosis on radiographs and numerous nodules with interstitial fibrosis on pathology.

Mycobacterial Disease

Mycobacterial disease is known to occur with increased frequency in persons with silicosis. Persons with chronic silicosis have an incidence of mycobacterial tuberculosis that is three times greater than that of age-matched controls. Those with acute and accelerated silicosis have the highest incidence of mycobacterial disease. Others exposed to silica but without silicosis might have an excess risk of developing tuberculosis.

Given the high incidence of tuberculosis in these patients, it is recommended that persons with silicosis or long-term exposure to crystalline silica should receive a tuberculin skin test. If the reaction is 10 mm or greater and there is no evidence of active tuberculosis, tuberculosis chemoprophylaxis should be administered. If symptoms or radiographic changes suggest the possibility of mycobacterial disease, routine or induced sputum should be obtained and bronchoscopy considered. If active tuberculosis is confirmed, standard tuberculosis therapy, with a regimen containing rifampin, should be administered. Similarly, if a nontuberculous mycobacterium is identified, standard therapy for that organism should be administered.

Obstructive Lung Disease and Lung Cancer

Exposure to crystalline silica has been associated with the development of obstructive lung disease, chronic bronchitis, and emphysema. These associations are more prominent in those with silicosis. The intensity of dust exposure appears to affect the development of obstructive lung diseases. Tobacco smoking can have an additive effect.

According to the International Agency for Research on Cancer, there is sufficient evidence to classify silica as carcinogenic in humans. Available studies are complicated by multiple confounders and selection biases. Despite this, the bulk of the evidence supports an increased risk of lung cancer in tobacco smokers with silicosis. The relation is less clear for never-smokers and for persons exposed to silica who do not have silicosis.

Other Associations

Evidence suggests a relation between appreciable silica exposure and the development of scleroderma. Less evidence is available to support an association with rheumatoid arthritis or systemic lupus erythematosus. Similarly, reports of renal disease associated with silica exposure require further evidence to confirm a link.