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Published: August 2010

Occupational Lung Disease

Raed A. Dweik

Peter J. Mazzone

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Exposure to dust in the workplace is associated with a variety of pulmonary and systemic illnesses. The term pneumoconiosis is derived from Greek and simply means “dusty lungs.” In current medical practice, the term is reserved for the permanent alteration of lung structure caused by inhalation of a mineral dust and the reaction of the lung tissue to this dust. The reactions that occur within the lungs vary with the size of the dust particle and its biologic activity. Some dusts (e.g., barium, tin, iron) do not result in a fibrogenic reaction in the lungs, but others can evoke a variety of tissue responses. Such responses include nodular fibrosis (silicosis), diffuse fibrosis (asbestosis), and macule formation with focal emphysema (coal worker’s disease). Still others (e.g., beryllium) can evoke a systemic response and induce a granulomatous reaction in the lungs. Pneumoconioses can appear and progress after the exposure has ceased. Regression does not occur, and treatment is mostly symptomatic and supportive.

As we move well into the 21st century, and due to improvements in industrial hygiene practices and dust control measures, we will probably be seeing less of the traditional pneumoconioses in the industrialized countries. We will, however, start seeing more of the immunologically mediated disorders related to more modern technologies, such as hard metal disease and chronic beryllium disease. In this chapter, we discuss a few of the traditional dust exposures (asbestos, silica, coal, and hard metals) and the illnesses they produce. Special emphasis is given to beryllium-induced lung disease because of its emerging role and the need for increased awareness to recognize persons at risk based on recent advances in the understanding of its pathophysiology.

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Asbestos-related Lung Disease

Exposure to asbestos occurs during its mining, milling, and transporting, as well as during the manufacture and application of asbestos-containing products. The most common industries in which exposure occurs are the construction and shipbuilding industries. The most common occupations are plumbing, pipefitting, insulating, and electrical work. This exposure can lead to a variety of lung diseases including pleural diseases and the pneumoconiosis asbestosis. Asbestos is also a known carcinogen.1-4

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 (Figure 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.

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 (Figure 2) in pathologic samples help to support the diagnosis.

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 (Figure 3).

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.

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Silica Exposure

Exposure to crystalline silica occurs when silica-containing rock and sand are encountered. This most commonly occurs in occupations associated with construction, mining, quarrying, drilling, and foundry work. A variety of conditions have been associated with inhalation of crystalline silica, including silicosis, tuberculosis, obstructive lung disease, and lung cancer.1,3-6

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 (Figure 4). Hilar adenopathy with eggshell calcification can be seen. Pulmonary function abnormalities do not invariably occur. Pathologically, the nodules are recognized as silicotic nodules.

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 (Figure 5).

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.

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Coal Dust Exposure

Deposition of coal dust in the lungs can lead to lung disease. Coal mining is the major source of exposure. The tissue reaction to coal dust inhalation is the development of a coal macule. Focal emphysema can form around the macule. This combination is termed a coal nodule and is the characteristic lesion of simple coal worker’s pneumoconiosis (CWP). In addition to CWP, coal dust exposure is also related to the development of airflow limitation, chronic bronchitis, and emphysema. Silica exposure often occurs in combination with coal dust exposure; thus, the previously described silica-related illness might also be seen.1,3

Simple CWP is usually without symptoms. Shortness of breath or a productive cough is often related to chronic bronchitis or airflow obstruction. Progressive massive fibrosis (PMF) can occur, more commonly when there has also been exposure to silica. Symptoms advance as the PMF worsens (Figure 6). Deaths from CWP continue to occur (Figure 7).

Given the common absence of symptoms, simple CWP is often a radiographic diagnosis. Chest imaging reveals small nodules with upper and posterior zone predominance. Hilar lymph node enlargement is not uncommon, although eggshell calcification does not generally occur. When PMF occurs, these small nodules coalesce, forming opacities larger than 1 cm. These lesions are odd-shaped, usually bilateral, and progressive, and they can cavitate or become calcified. Care must be taken because lesions diagnosed radiographically as PMF are often shown later to have been tumors, tuberculosis scars, or Caplan’s nodules (see later).

Simple CWP tends to have little effect on lung function. Airflow limitation, restriction, and a reduction in diffusing capacity can all be seen when PMF develops. Pulmonary hypertension can develop in advanced disease.

Complications of CWP include a higher incidence of mycobacterial disease (although not as high as with silicosis), and an increased risk of stomach cancer. Tuberculin skin testing, chemoprophylaxis, and treatment of active tuberculosis are as recommended in silicosis. Caplan’s syndrome is a nodular form of CWP seen in persons with rheumatoid arthritis. The nodules are multiple, tend to be larger than typical coal nodules, develop over short periods of time, and cavitate more often. These findings usually occur concomitantly with the joint manifestations, active arthritis, and the presence of circulating rheumatoid factor.

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Hard Metal Disease

Hard metal, or cemented tungsten carbide, is found in tools for high-speed cutting, drilling, grinding, or polishing of other metals or hard materials. The consensus is that the agent responsible for the disease is the cobalt used as a catalyst to promote the binding of tungsten to carbon rather than the tungsten carbide itself. Workers in industries that manufacture cutting tools, drills, and the like are at highest risk. However, users of such tools (e.g., dental laboratories, sharpeners of saws, and diamond polishers) can also be exposed.

Work-related illness in hard metal disease includes asthma and interstitial lung disease. The disease can manifest acutely with rapidly progressing dyspnea after relatively short exposure, or it can manifest more insidiously and usually after long exposure. An acquired hypersensitivity can play a role in the development of a hypersensitivity bronchitis or asthma-like picture in a small percentage of workers in hard metal. The interstitial fibrosis is characterized by fibrosing alveolitis, interstitial pneumonitis, and multinucleated giant cells (Figure 8) also recovered from the bronchoalveolar lavage. Both interstitial and area disease can occur in the same patient. Diagnosis is based on an exposure history, a compatible clinical presentation, and pathologic findings. Treatment is mostly supportive. Corticosteroids have been used to treat patients with acute presentation.7,8

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Beryllium-induced Lung Disease

Beryllium is an extremely light metal with a high modulus of elasticity (stiffness), a low coefficient of thermal expansion, high thermal and electrical conductivity, and a high melting point. Because of these unique properties, beryllium is used in many industries (Box 1). Pure beryllium metal is useful in the nuclear industry as a moderator of neutrons, increasing the effectiveness of the chain reaction. More often, it is formulated as an alloy or an oxide.9,10

Box 1 Common Uses of Beryllium
Applications
Aircraft brakes and landing gear
Aircraft engines
Automotive electronics
Ball bearings
Ceramic applications
Computer electronics
Electrical components
Electrical contacts
Gears
Golf clubs
Inertial guidance systems
Injection and blow mold tooling
Laser tubes
Rocket engine liners
Spark plugs
Springs
Turbine rotor blades
Welding electrodes
X-ray tube windows
Industries
Gas industry
Oil industry

© 2004 The Cleveland Clinic Foundation.

Prevalence and Risk Factors

Historically, acute toxicity was associated with occupational exposures to concentrations of soluble beryllium salts greater than 100 μg/m3. With the advent of industrial control measures to minimize air levels, acute pulmonary syndromes have virtually disappeared.

Persons who work with beryllium continue to be at risk for developing chronic beryllium disease (CBD or berylliosis). This is a granulomatous lung disease similar to sarcoidosis that is caused by a delayed-type hypersensitivity reaction in which there is a proliferation of beryllium-specific T cells.11 About 10% of exposed persons develop beryllium hypersensitivity, and about 5% of those exposed develop CBD (Figure 9). The most significant exposure is in the occupational setting. Occupations with the highest potential for exposure are those involved with primary production, metal machining, and reclaiming scrap alloys. Other high-exposure areas are in the nuclear power, aerospace, and electronic industries (Box 2).12,13

In addition to environmental exposure, genetic predisposition seems to have a major role in the development of CBD. A variant of the human leukocyte antigen (HLA-DPb1 [Glu69]) is found in 80% to 97% of patients with CBD and in only 30% of controls.14,15

Box 2 Industries that Use Beryllium
Industries that Use Beryllium Heavily
Beryllium and beryllium alloy machine shops
Beryllium extraction
Electronics
Nuclear weapons manufacturing
Industries that Use Beryllium Less Heavily
Aerospace
Automotive
Ceramics
Computers
Dental appliances

© 2004 The Cleveland Clinic Foundation.

Signs and Symptoms

The lung is the primary organ affected by CBD. Other organs can also be affected, including the extrapulmonary lymph nodes, skin, salivary glands, liver, spleen, kidneys, bone, myocardium, and skeletal muscle. Symptoms are usually nonspecific and occur late in the course of the disease. Dyspnea is the most common symptom, but some patients also present with cough, chest pain, arthralgia, fatigue, and weight loss. Physical signs, like symptoms, occur late in the course of disease and include inspiratory crackles on pulmonary auscultation, lymphadenopathy, skin lesions, and hepatosplenomegaly. Pulmonary function testing reveals an obstructive pattern in 39% and a restrictive pattern in 20% of patients with CBD. DLCO (the lung diffusion capacity for carbon monoxide) also declines over time in 36% of persons. However, the most sensitive test is abnormalities in gas exchange during exercise.

A chest radiograph is normal in about one half the patients with documented CBD. Abnormal findings in the other one half include hilar adenopathy or increased interstitial markings, or both. High-resolution CT (HRCT) of the chest is more sensitive than chest radiography. Typical findings on HRCT are ground-glass opacification (Figure 10), parenchymal nodules, or septal lines. HRCT, however, can show negative results in up to 25% of patients with documented CBD.9,10,16,17

Diagnosis

The diagnosis of CBD is based on the presence of a positive blood test or bronchoalveolar lavage beryllium-specific lymphocyte proliferation test (BeLPT) and the presence of non-necrotizing granuloma on lung biopsy.

The blood BeLPT is the screening test of choice to identify beryllium workers who develop beryllium sensitization or CBD. It involves exposing peripheral blood mononuclear cells in vitro to beryllium salts at varying concentrations for varying time intervals, looking for cell proliferation. This test is performed only in select, specialized laboratories around the country (Box 3).18,19 Patients who have a positive blood BeLPT but no lung pathology are considered to be sensitized to beryllium but do not have CBD. They remain, however, at a lifelong risk for developing CBD.

Box 3 Select Locations for Beryllium Lymphocyte Proliferation Testing in the United States
Cleveland Clinic Foundation
Department of Clinical Pathology, L40
9500 Euclid Avenue
Cleveland, OH 44195-0001
Phone: (216) 444-2200 or 1-800-223-2273, ext 48844 or 55763
Fax: (216) 445-8160
Hospital of the University of Pennsylvania
Pulmonary Immunology Laboratory
833 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-4283
Phone: (215) 573-9906
Fax: (215) 349-5172
National Jewish Center for Immunology and Respiratory Medicine
Cellular Immunology Tests
Pulmonary Division and Occupational/
Environmental Medicine Division
1400 Jackson Street
Denver, CO 80206
Phone: (303) 388-4461
Specialty Laboratories, Inc.
OncQuest
2211 Michigan Avenue
Santa Monica, CA 90404-3900
Phone: (310) 828-6543 or 1-800-421-4449

© 2004 The Cleveland Clinic Foundation.

There are many similarities between CBD and sarcoidosis (Table 1). Without a suspicion of beryllium exposure, almost all cases of CBD are diagnosed as sarcoidosis. For the same reason, all patients with sarcoidosis should have a detailed occupational history to exclude history of exposure to beryllium.9,10

Table 1 Clinical and Laboratory Features of Chronic Beryllium Disease and Sarcoidosis
Feature Chronic Beryllium Disease Sarcoidosis
Occupational exposure to beryllium Yes No
Onset Acute or insidious Acute or insidious
Respiratory symptoms Predominant organ affected Predominant organ affected
Erythyma nodosum No Yes
Dermatitis Yes No
Cardiac Rare Common
Pulmonary physiology Gas exchange abnormalities are common
Obstruction early
Mixed obstruction and restriction, or pure restriction, late
Gas exchange abnormalities are common
Restriction, obstruction, or mixed pattern
Bilateral hilar adenopathy Uncommon Common
Infiltrates Diffuse nodular or linear opacitiesCan be absent Nodular and/or linear opacitiesMay be more focal than in CBD
Computed tomography Small nodules, septal lines, ground-glass appearance, adenopathy Small nodules, septal lines, adenopathy
Beryllium lymphocyte proliferation test Positive Negative
Granulomas Noncaseating granuloma Noncaseating granuloma
Other histology Diffuse mononuclear cell infiltrate is common
Bronchial submucosa is involved occasionally
Diffuse mononuclear cell infiltrate is common
Bronchial submucosa is involved occasionally
Beryllium in tissues Yes No
Tuberculin skin test Negative Negative
Kveim skin test Negative Positive
Beryllium patch skin test Positive Negative
Elevated serum ACE Uncommon Common
Response to steroid therapy Often stabilizes disease, can improve pulmonary physiology and symptoms, usually requires continuous therapy Often stabilizes disease that has not spontaneously remitted, can require continuous therapy
Prognosis Variable; cor pulmonale and progressive fibrosis in some patients, more benign in others Good prognosis for approximately 80% of patients, may progress to end-stage fibrosis and cor pulmonale

ACE, angiotensin-converting enzyme; CBD, chronic beryllium disease.

© 2004 The Cleveland Clinic Foundation.

Flexible fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy usually necessary to confirm a suspected diagnosis of CBD. Bronchoscopy is also helpful in excluding other possible causes with similar presentations, such as hypersensitivity pneumonitis or mycobacterial or fungal infection. The presence of non-necrotizing granulomas on transbronchial biopsy is the hallmark of CBD and is diagnostic in the appropriate clinical and epidemiologic settings. The granulomas in CBD are indistinguishable from sarcoid granulomas (Figure 11). This is why exposure to beryllium (confirmed by occupational history, a positive BeLPT test, or beryllium in the tissue) is an integral part of the diagnosis of CBD. Patients with CBD usually have lymphocytosis (>20% lymphocytes in fluid from bronchoalveolar lavage). The BeLPT can also be performed on mononuclear cells from bronchoalveolar lavage fluid. An open lung biopsy is rarely needed but could be resorted to if the transbronchial biopsy is negative and the suspicion for CBD remaines high. Although the diagnostic yield is slightly higher than in transbronchial biopsy, the risk is also significantly higher. Serum levels of angiotensin-converting enzyme inhibitors may be high in CBD as in other granulomatous diseases, but this has no diagnostic value.9,10,12,18

Treatment

All patients with CBD should be advised to avoid any further beryllium exposure. Although there is no proof that cessation of exposure to beryllium will improve the disease or halt its progression, it is prudent to avoid further exposure due to the immune-mediated nature of the disease. There is currently no cure for CBD, and no controlled studies for CBD are available. However, based on anecdotal reports and on the pathogenesis of the disease (immune mediated), and because of the similarities with sarcoidosis, CBD is treated with corticosteroids. Because therapy is not curative and has significant side effects, it is recommended only in patients who are symptomatic or demonstrate decline in their pulmonary function. In patients in whom corticosteroids fail or who develop significant side effects, methotrexate may be considered. In end-stage cases, lung transplantation may be considered.9,10

In summary, chronic beryllium disease (CBD, berylliosis) is an occupationally acquired granulomatous lung disease similar to sarcoidosis. It is caused by exposure to beryllium in genetically susceptible persons. CBD should be suspected in persons with beryllium exposure who present with pulmonary symptoms or have a positive screening blood BeLPT.

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Summary

  • Exposure to dust in the workplace is associated with a variety of pulmonary and systemic illnesses (pneumoconiosis).
  • Pneumoconioses can appear and progress after the exposure has ceased. Regression does not occur, and treatment is mostly symptomatic and supportive.
  • Asbestos exposure can lead to a variety of lung diseases including pleural diseases and asbestosis. Asbestos is also a known carcinogen.
  • Many conditions have been associated with inhalation of crystalline silica, including silicosis, tuberculosis, obstructive lung disease, and lung cancer.
  • Simple coal worker’s pneumoconiosis tends to have little effect on lung function. Airflow limitation, restriction, and a reduction in diffusing capacity can all be seen when progressive massive fibrosis develops.
  • Chronic beryllium disease (berylliosis) is an occupationally acquired granulomatous lung disease similar to sarcoidosis. It is caused by exposure to beryllium. Chronic beryllium disease should be suspected in patients with beryllium exposure who present with pulmonary symptoms or have a positive screening blood beryllium-specific lymphocyte proliferation test.

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Suggested Readings

  • Beckett WS: Occupational respiratory diseases. N Engl J Med 2000;342:406-413.
  • Beckett WS, Abraham J, Becklake M, et al: Adverse effects of crystalline silica exposure.
  • Official statement of the American Thoracic Society Committee of the Scientific Assembly on Environmental and Occupational Health. Am J Respir Crit Care Med 1997;155:761-768.
  • Berlin JM, Taylor JS, Sigel JE, et al: Beryllium dermatitis. J Am Acad Dermatol 2003;49:939-941.
  • Cullen MR: Respiratory diseases from hard metal exposure. A continuing enigma. Chest 1984;86:513-514.
  • Culver DA, Dweik RA: Chronic beryllium disease. Clin Pulm Med 2003;10:72-79.
  • Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med Sep 15 2004;170(6):691-715.
  • Dweik RA: Berylliosis. Available at http://www.emedicine.com/med/topic222.htm (accessed March 20, 2009).
  • 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. PDF available at http://www.cdc.gov/niosh/docs/2000-105/2000-105.html (accessed March 20, 2009).
  • National Institute for Occupational Safety and Health (NIOSH): NIOSH Hazard Review: Health effects of occupational exposure to respirable crystalline silica. DHHS (NIOSH) publication no. 2002-129, April 2002. Available at http://www.cdc.gov/niosh/docs/2002-129/02-129a.html (accessed March 20, 2009).
  • Wagner GR: Asbestosis and silicosis. Lancet 1997;349:1311-1315.

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References

  1. 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. PDF available at http://www.cdc.gov/niosh/docs/2000-105/2000-105.html (accessed March 20, 2009).
  2. American Thoracic Society: Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med 2004;170(6):691-715.
  3. Beckett WS: Occupational respiratory diseases. N Engl J Med 2000; 342:406-413.
  4. Wagner GR: Asbestosis and silicosis. Lancet 1997;349:1311-1315.
  5. Beckett WS, Abraham J, Becklake M, et al: Adverse effects of crystalline silica exposure. Official statement of the American Thoracic Society Committee of the Scientific Assembly on Environmental and Occupational Health. Am J Respir Crit Care Med 1997;155:761-768.
  6. National Institute for Occupational Safety and Health (NIOSH): NIOSH Hazard Review: Health effects of occupational exposure to respirable crystalline silica. DHHS (NIOSH) publication no. 2002-129, April 2002. Available at http://www.cdc.gov/niosh/docs/2002-129/02-129a.html (accessed March 20, 2009).
  7. Cullen MR: Respiratory diseases from hard metal exposure. A continuing enigma. Chest 1984;86:513-514.
  8. Sprince NL, Oliver LC, Eisen EA, et al: Cobalt exposure and lung disease in tungsten carbide production. A cross-sectional study of current workers. Am Rev Respir Dis 1988;138:1220-1226.
  9. Dweik RA: Berylliosis. Available at http://www.emedicine.com/med/topic222.htm (accessed March 20, 2009).
  10. Culver DA, Dweik RA: Chronic beryllium disease. Clin Pulm Med 2003;10:72-79.
  11. Saltini C, Winestock K, Kirby M, et al: Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells. N Engl J Med 1989;320:1103-1109.
  12. Newman LS Lloyd J, Daniloff E: The natural history of beryllium sensitization and chronic beryllium disease. Environ Health Perspect 1996;104(Suppl 5):937-943.
  13. Kreiss K, Mroz MM, Zhen B, et al: Risks of beryllium disease related to work processes at a metal, alloy, and oxide production plant. Occup Environ Med 1997;54:605-612.
  14. Richeldi L, Sorrentino R, Saltini C: HLA-DPB1 glutamate 69: A genetic marker of beryllium disease. Science 1993;262:242-244.
  15. Saltini C, Richeldi L, Losi M, et al: Major histocompatibility locus genetic markers of beryllium sensitization and disease. Eur Respir J 2001;18: 677-684.
  16. Saber W, Dweik RA: A 65-year-old factory worker with dyspnea on exertion and a normal chest x-ray. Cleve Clin J Med 2000;67:791-800.
  17. Berlin JM, Taylor JS, Sigel JE, et al: Beryllium dermatitis. J Am Acad Dermatol 2003;49:939-941.
  18. Rossman MD, Kern JA, Elias JA, et al: Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease. Ann Intern Med 1988;108:687-693.
  19. Barna BP, Culver DA, Yen-Lieberman B, et al: Clinical application of beryllium lymphocyte proliferation testing. Clin Diagn Lab Immunol 2003;10:990-994.

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