Asbestosis--a primer and an update.

Asbestosis is one of many pneumoconioses. The term pneumoconiosis is derived from the Greek words pneumo and konia meaning "lung" and "dust," respectively. It encompasses pulmonary conditions caused by the inhalation of inorganic, or mineral dusts. Pneumoconioses fall under the broad category of interstitial lung disease, and are also called occupational lung diseases or environmental lung diseases. Pneumoconioses differ from another form of interstitial lung disease called hypersensitivity pneumonitis, which is caused by the inhalation of organic material. An example is farmer's lung, which results from the inhalation of the microorganism Micropolyspora faeni found in moldy hay.

Pneumoconioses are generally characterized as having an insidious progression and a protracted clinical latency. In other words, the signs and symptoms typically surface and lead to a diagnosis many years following the initial exposure to the inhaled inorganic dust. Several factors are influential in determining the clinical presentation of these diseases. These factors include (1) the chemical nature of the inorganic dust, (2) the diameter or length of the inhaled material, (3) the magnitude (concentration and duration) of the exposure, and (4) host factors, e.g., the person's pulmonary defense mechanisms and immunologic response.

ASBESTOS HISTORY & MINERALOGY

Asbestos, which means inextinguishable or unquenchable, is an ancient mineral. It has been used throughout history because of its durability, resistance to corrosion, and heat retardant nature. As early as 4,000 BC, asbestos was used for wicks and candles. Around 3,000 BC bodies of Egyptian pharaohs were wrapped in asbestos clothes to offset the ravages of time. After visiting an asbestos mine in China during the latter half of the 13th century, Marco Polo concluded that asbestos was a stone, and laid to rest the myth that asbestos was the hair of a wooly lizard, in the 1939-film, "The Wizard of Oz," the Wicked Witch of the West appeared on a broom made of asbestos. Currently, the solid rocket boosters of the Space Shuttles are insulated with asbestos.

During the late 1960s, evidence emerged indicating that asbestos fibers were a dangerous health risk. By the 1970s, the federal government began taking legislative action to regulate asbestos use. During the 1980s, the concern regarding asbestos resulted in a new industry focused on asbestos abatement. Legislation has not banned the use of asbestos, but it is not commonly used by manufacturers in the United States any more because of health concerns and liability issues. Nonetheless, the international use of asbestos remains strong. Imported materials may possess asbestos, and consequently may pose health threats.

The Occupational Safety and Health Administration (OSHA) has established permissible exposure limits for asbestos workers. Employee exposure must not exceed 0.1 fiber per cubic centimeter (f/cc) of air, averaged over an 8-hour work shift. Short term exposure must also be limited to not more than 1 f/cc of air, averaged over 30 minutes. OSHA also prohibits the rotation of employees to achieve compliance with either permissible exposure limit.

Asbestos is a generic term for naturally occurring fibrous silicates that embodies two geologic varieties. These two types are serpentine and amphibole. In the serpentine variety, the asbestos fibers are curly and flexible. In the amphibole variety, the fibers are straight, stiff, and brittle. A single form of serpentine asbestos, called, chrysotile or white asbestos, is the most commonly used form of asbestos, and accounts for approximately 95% of the asbestos found in buildings throughout the United States. The rigid, stiff amphiboles are represented by five forms: crocidolite, amosite, anthrophylite, tremolite, and actinolite. Crocidolite (blue asbestos) was commonly used in high temperature applications. Amosite (brown asbestos) is used primarily as a fire retardant in thermal insulation products and ceiling tiles. Amphiboles, crocidolite in particular, are considered to be more pathologic than serpentine chrysotile, especially with respect to the production of malignant pleural tumors, i.e., mesotheliomas.

The greater pathogenicity associated with amphiboles is attributed to the rigidity of its fibers. These fibers are more likely to be more aerodynamic and deposit in the gas exchange regions of the lungs where many penetrate the pulmonary interstitium. The serpentine chrysotiles, because of their coiled, pliable nature, appear to impact more in the upper respiratory tract where they can be evacuated from the body via the mucociliary blanket.

EPIDEMIOLOGY

Asbestosis is caused by the inhalation of asbestos fibers. This disease develops in persons who are chronically exposed to asbestos or asbestos-laden materials. Persons who have occupations, or persons who reside in environments, that subject them to the inhalation of asbestos fibers are at risk for developing asbestosis. Persons at highest risk for developing asbestosis are those who are directly involved in the handling of asbestos in the workplace. Workers having the greatest risk include those involved in manufacturing asbestos products, constructing, remodeling, and demolishing buildings, and working in shipyards. Spouses and children of asbestos workers often experience indirect exposure. For example, the wife of an asbestos worker may shake out the worker's clothes before laundering them and become subjected to airborne asbestos fibers. People who live in proximity to industrial plants where asbestos products are manufactured are also at risk of developing the disease through environmental exposure.

Asbestosis has been blamed in the deaths of 876 United States citizens from 1979 to 1992. Current projections are that over 200,000 deaths in the United States will be attributed to asbestosis by the year 2030. These asbestos-related death projections include malignancies. When exposure to asbestos fibers is combined with cigarette smoking, the incidence of bronchogenic carcinoma is approximately 55-fold greater than normal.

Signs and Symptoms

The signs and symptoms of asbestosis typically emerge decades after exposure to asbestos has occurred, usually 20 or more years. The signs and symptoms tend to include basal crackles, small radiographic opacities, obscured left heart border, pulmonary function spirometry tests demonstrating restriction, obstruction or mixed patterns, reduced DLCO, digital clubbing, chest tightness, chest pain, loss of appetite, difficulty sleeping, shortness of breath, persistent, nonproductive cough

The diagnosis of asbestosis, like any other pneumoconiosis, must include a thorough occupational, environmental, and family history.

PATHOPHYSIOLOGY

The mechanism of production of pulmonary and pleural lesions caused by the inhalation of asbestos fibers appears to involve insults to the peripheral airways, alveolar walls, and the pulmonary interstitium. Inflammation, caused by the release of mediators and oxygen radicals from alveolar macrophage and neutrophil activity in these regions, leads to fibrosis.

The pathophysiology associated with asbestosis varies according to the concentration and duration of exposure and the type of fiber inhaled. If the magnitude of exposure is low, and if the fibers are removed by alveolar macrophages, alveolar inflammation resolves. Despite a low magnitude of exposure, failure of the lungs to rid themselves of inhaled fibers may result in minimal peripheral airway disease. In the face of high exposure and retained asbestos fibers, inflammation is the likely consequence, along with the recruitment of fibroblasts to the sites of retention. A proliferation of fibroblasts is followed by the deposition of collagen at those sites. If asbestos exposure continues, permanent lung damage occurs, irreversible alveolar damage develops, and chronic interstitial fibrosis ensues. This scenario represents asbestosis.

When asbestos fibers penetrate and deposit on alveolar surfaces, alveolar macrophages attempt to engulf them and remove them from the site of deposition. The nature of certain asbestos fibers resists this removal process. This resistance to alveolar macrophage removal is described as retention and is related to the form of asbestos fiber inhaled. The serpentine chrysotile fiber is more readily removed by alveolar macrophages compared with the amphibole amosite and crocidolite varieties. The retention of asbestos fibers in the lungs is the basis for the inflammation and fibrosis associated with asbestosis. Clinical evidence demonstrates that asbestos fibers less than or equal to 3 millimicrons long are phagocytized by alveolar macrophages. The speculation is that these macrophages then move to the lymphatic system, and ultimately enter the intrapleural space.

The fate of longer asbestos fibers differs. They are retained after unsuccessful attempts by numerous macrophages to engulf them and to remove them from the lungs. These retained asbestos fibers eventually develop an iron-protein coating. The iron-protein coating enveloping an asbestos core is called an asbestos body or ferruginous body. The presence of numerous ferruginous bodies is suggestive of asbestos exposure. These asbestos bodies can appear in sputum or bronchoalveolar lavage solution.

Asbestosis has a tendency to manifest itself predominantly in the lower lobes and in the subpleural regions. However, it can manifest itself in other lung regions in the presence of highly intense and protracted asbestos exposure. The appearance of asbestos fibers in the parietal pleura resulting in the formation of subpleural plaques is inexplicable.

Alveolar inflammation, lung tissue fibrosis, and collagen deposition contribute to diminished pulmonary function, including a decreased DLCO, and a decreased pulmonary compliance. The hypoxemia that occurs often contributes to polycythemia and pulmonary hypertension. The increased work imposed on the right ventricle caused by the increased blood viscosity and increased vascular resistance ultimately leads to cor pulmonale.

THE MESOTHELIUM 

The mesothelium is a thin layer of specialized cells lining the interior aspect of the thoracic cavity (parietal pleura), the lung parenchyma (visceral pleura), the peritoneal cavity, and the pericardial cavity. The mesothelium forms the simple squamous epithelium that covers the surface of all true serous membranes. It provides protection to the organs of the pleura, pertitoneum, and pericardium by secreting serous fluid which acts as a lubricant. For example, as the lungs inflate and deflate, the serous fluid in the pleural space enables the lungs to move freely against the chest wall throughout the respiratory cycle.

CLINICAL MANIFESTATIONS OF ASBESTOS EXPOSURE

Asbestosis is one of four distinct and often overlapping clinical manifestations of asbestos exposure. The other three presentations are asbestos-related pleural disease, bronchogenic carcinoma, and malignant mesothelioma. Asbestos-related pleural disease pertains to the presence of pleural plaques and calcification resulting from exposure. How fibers arrive in the pleura is uncertain. The speculation is alveolar macrophages deposit them there as the macrophages transport asbestos fibers through the lymphatic system after phagocytizing them in the alveoli. This form of asbestos exposure is devoid of clinical symptoms. Spirometry tends to reflect a restrictive abnormality caused by pleural fibrosis.

Bronchogenic carcinoma tends to develop two to three times more frequently in people exposed to asbestos, but the combination of asbestosis exposure and cigarette smoking heightens the predisposition to bronchogenic carcinoma by about 55-fold. To place the incidence of bronchogenic carcinoma among asbestos workers in perspective, one needs to realize that among the general population one in nine cigarette smokers develops lung cancer.

The histologic varieties of bronchogenic carcinoma resulting from asbestos exposure include squamous cell, adenocarcinoma, large cell undifferentiated, and small-cell lung cancer. The mechanism by which asbestos exposure causes bronchogenic carcinoma is not known. However, asbestos appears to act as an initiator or a promoter of carcinogenesis.

Malignant pleural mesothelioma is a rare-occurring neoplasm among the general population in the US. Asbestos workers, on the other hand, experience a morbidity of 3% to 10% from mesothelioma. This disease develops about 20 to 50 years following initial asbestos exposure, making mesothelioma the asbestos-related lung disease with the longest latency period. The symptoms include chest pain, shortness of breath, dyspnea, persistent cough, difficulty swallowing, loss of appetite, and weight loss. Large exudative pleural effusions are also characteristic of this condition.

The diagnosis is difficult to make because the signs and symptoms are general, and because other tumors viewed via chest radiography and CT scans have a similar appearance to mesothelioma. Diagnosing mesotheliomas requires biopsy and pathological testing.

Three varieties of mesotheliomas exist. Approximately, 50% to 70% of mesotheliomas are of the epithelioid type. The other two, sarcomatoid and mixed or biphasic, account for 7% to 20% and 20% to 35%, respectively. Regardless of the type of mesothelioma present, no satisfactory treatment for this condition exists. Following the diagnosis of mesothelioma, death tends to occur with two years. The treatment available includes surgey, pleurectomy/decortication, extrapleural pneumonectomy, chemotherapy, and radiation therapy.

Mesothelioma of the peritoneum can also develop as asbestos workers swallow asbestos-laden mucus transported to the larynx via the mucociliary blanket. Asbestos fibers can also enter the peritoneum through the lymphatic system. Peritoneal mesotheliomas are treated with chemotherapy, radiation therapy, and surgery.

As with any pneumoconiosis, prevention is paramount. Vigilance and safety in the work place help to control and prevent theses diseases. Industry, the health care community and government can all contribute to improving the quality of the work place environment to minimize the risk of occupational lung disease to workers. Unfortunately, in the case of asbestos-related lung diseases, no cure exists. Despite the removal of a person from a hazardous environment, the disease process progresses.