Pneumoconioses PDF

# Pneumoconioses Pneumoconiosis is a term originally coined to describe lung disorders caused by inhalation of mineral dusts. The term has since been broadened to include diseases induced by organic and inorganic particulates, and some experts also regard chemical fume- and vapor-induced lung disea...

# Pneumoconioses Pneumoconiosis is a term originally coined to describe lung disorders caused by inhalation of mineral dusts. The term has since been broadened to include diseases induced by organic and inorganic particulates, and some experts also regard chemical fume- and vapor-induced lung diseases as pneumoconioses. The mineral dust pneumoconioses—most commonly caused by inhalation of coal dust, silica, and asbestos—usually stem from exposure in the workplace. In the case of asbestos, an increased risk for cancer extends to the family members of asbestos workers and to individuals exposed outside of the workplace. ## Pathogenesis The reaction of the lung to mineral dusts depends on the size, shape, and solubility of the particles and their inherent pro-inflammatory properties. For example, particles greater than 5 to 10 µm are unlikely to reach distal airways, and particles smaller than 0.5 µm move into and out of alveoli, often without significant deposition and injury. Particles that are 1 to 5 µm in diameter are of greatest concern as they tend to lodge at the bifurcation of the distal airways. Coal dust is relatively inert, and large amounts must be deposited in the lungs before lung disease is clinically detectable. Silica, asbestos, and beryllium stimulate greater immune response than coal dust, resulting in fibrotic reactions at lower concentrations. The pulmonary alveolar macrophage is a key cellular element in the initiation and perpetuation of inflammation, lung injury, and fibrosis. Following phagocytosis by macrophages, many particles activate the inflammasome and induce production of the pro-inflammatory cytokine IL-1 as well as the release of other factors. These factors initiate an inflammatory response that leads to fibroblast proliferation and collagen deposition. Some of the inhaled particles may reach the lymphatics either by direct drainage or within migrating macrophages and thereby initiate an immune response to components of the particulates and/or to self proteins that are modified by the particles. This leads to an amplification and extension of the local reaction. Tobacco smoking worsens the effects of all inhaled mineral dusts, more so with asbestos than other particles. ## Coal Workers' Pneumoconiosis Dust reduction in coal mines has greatly reduced the incidence of coal dust-induced disease; however, there is an increasing prevalence of Coal Workers' Pneumoconiosis (CWP) in older miners in the United States, particularly in the region known as Appalachia. The spectrum of lung findings in coal workers is wide, ranging from asymptomatic anthracosis, in which carbon pigment deposits without a perceptible cellular reaction; to simple CWP, in which macrophages accumulate with little to no pulmonary dysfunction; to complicated CWP or progressive massive fibrosis (PMF), in which fibrosis is extensive and lung function is compromised (see Table 11.3). Although statistics vary, it seems that less than 10% of cases of simple CWP progress to PMF. Of note, PMF is a generic term that is applied to confluent pulmonary fibrosis; it may arise in any of the pneumoconioses discussed here. Although coal is mainly carbon, coal mine dust contains a variety of trace metals, inorganic minerals, and crystalline silica. In general, the risk of CWP is higher in miners working in areas in which coal has higher levels of contaminating chemicals and minerals. ## Morphology - **Pulmonary anthracosis** is the most innocuous coal-induced pulmonary lesion in coal miners and is also commonly seen in urban dwellers and individuals who smoke tobacco. Inhaled carbon pigment is engulfed by alveolar or interstitial macrophages, which then accumulate in the connective tissue along the pulmonary and pleural lymphatics and in draining lymph nodes. - **Simple CWP** is characterized by the presence of coal macules and larger coal nodules. The coal macule consists of dust-laden macrophages and small amounts of collagen fibers arrayed in a delicate network. Although these lesions are scattered throughout the lung, the upper lobes and upper zones of the lower lobes are more heavily involved. In due course, centrilobular emphysema may occur. - **Complicated CWP (PMF)** occurs on a background of simple CWP by coalescence of coal nodules and generally develops over many years. It is characterized by multiple, dark black scars larger than 2 cm and sometimes up to 10 cm in diameter that consist of dense collagen and pigment (Fig. 11.16). ## Clinical Features CWP is usually a benign disease that produces little decline in lung function. In those in whom PMF develops, there is increasing pulmonary dysfunction, pulmonary hypertension, and cor pulmonale. Progression from CWP to PMF has been linked to exposure to higher coal dust levels and to total dust burden. Once established, PMF tends to progress even in the absence of further exposure. After taking smoking-related risk into account, there is no increased frequency of lung carcinoma in coal miners, a feature that distinguishes CWP from both silica and asbestos exposures (discussed next). # Silicosis Silicosis is currently the most prevalent chronic occupational disease in the world. It is caused by inhalation of crystalline silica, mostly in occupational settings. Workers involved in sandblasting and hard-rock mining are at particularly high risk. Silica occurs in both crystalline and amorphous forms, but crystalline forms (including quartz, cristobalite, and tridymite) are by far the most toxic and fibrogenic. Of these, quartz is most commonly implicated in silicosis. After inhalation, silica particles are ingested by alveolar macrophages, leading to lysosomal damage, activation of the inflammasome, and release of inflammatory mediators, including IL-1, TNF, lipid mediators, oxygen-derived free radicals, and fibrogenic cytokines. ## Morphology - Silicotic nodules in their early stages are tiny, barely palpable, discrete, pale-to-black (if coal dust is present) nodules in the upper zones of the lungs (Fig. 11.17). Microscopically, silicotic nodules have concentrically arranged hyalinized collagen fibers surrounding an amorphous center. The "whorled" appearance of the collagen fibers is quite characteristic (Fig. 11.18). Examination of the nodules by polarized microscopy reveals weakly birefringent silica particles, primarily in the center of the nodules. As the disease progresses, individual nodules may coalesce into hard, collagenous scars, with eventual progression to PMF. The intervening lung parenchyma may be compressed or overexpanded, and a honeycomb pattern may develop. Fibrotic lesions may also occur in hilar lymph nodes and the pleura. ## Clinical Features Silicosis is usually detected in asymptomatic workers on routine chest radiographs, which typically show a fine nodularity in the upper zones of the lung. Shortness of breath does not develop until late in the course, after PMF is present. Many patients with PMF develop pulmonary hypertension and cor pulmonale. The disease is slowly progressive, often impairing pulmonary function to a degree that severely limits physical activity. Silicosis is associated with an increased susceptibility to tuberculosis, perhaps because crystalline silica may inhibit the ability of pulmonary macrophages to kill phagocytosed mycobacteria. Nodules of silicotuberculosis often contain a central zone of caseation. Most evidence suggests that silicosis is also associated with modestly increased risk of lung cancer. # Asbestos-Related Diseases Asbestos is a family of crystalline hydrated silicates with a fibrous geometry. Occupational exposure to asbestos is linked to multiple pulmonary pathologies, including (1) parenchymal interstitial fibrosis (asbestosis); (2) localized fibrous plaques, or, rarely, diffuse fibrosis in the pleura; (3) pleural effusions; (4) lung carcinoma; (5) malignant pleural and peritoneal mesothelioma; and (6) laryngeal carcinoma. An increased incidence of asbestos-related cancers in family members of asbestos workers is due to residual asbestos particles on the workers' clothing. ## Pathogenesis As with silica crystals, once phagocytosed by macrophages, asbestos fibers activate the inflammasome and damage phagolysosomal membranes, stimulating the release of pro-inflammatory factors and fibrogenic mediators. In addition to cellular and fibrotic lung reactions, asbestos probably also functions as both a tumor initiator and a promoter. Some of the oncogenic effects of asbestos on the mesothelium are mediated by free radicals induced by asbestos fibers, which preferentially localize in the distal lung close to the mesothelial layer. It is also likely that toxic chemicals adsorbed onto the asbestos fibers contribute to their pathogenicity. For example, the adsorption of carcinogens in tobacco smoke onto asbestos fibers may be the basis for the strong synergy between tobacco smoking and the development of lung carcinoma in asbestos workers. ## Morphology - Asbestosis is marked by diffuse pulmonary interstitial fibrosis and the presence of asbestos bodies, golden brown, fusiform or beaded rods with a translucent center. They consist of asbestos fibers coated with an iron-containing proteinaceous material (Fig. 11.19). Apparently, asbestos bodies are formed when macrophages attempt to phagocytose asbestos fibers; the iron "crust" is derived from ferritin. - In contrast with CWP and silicosis, asbestosis begins in the lower lobes and subpleurally, spreading to the middle and upper lobes of the lungs as the fibrosis progresses. Contraction of the fibrous tissue distorts the normal architecture, creating enlarged air spaces enclosed within thick fibrous walls; eventually, the affected regions become honeycombed. Simultaneously, fibrosis develops in the visceral pleura, causing adhesions between the lungs and the chest wall. The scarring may trap and narrow pulmonary arteries and arterioles; this, along with worsening lung function, may lead to pulmonary hypertension and cor pulmonale. - Pleural plaques are the most common manifestation of asbestos exposure. They consist of well-circumscribed plaques of dense collagen (Fig. 11.20), often containing calcium. They develop most frequently on the anterior and posterolateral aspects of the parietal pleura and over the domes of the diaphragm. Uncommonly, asbestos exposure induces pleural effusion or diffuse pleural fibrosis. ## Clinical Features The clinical findings in asbestosis are indistinguishable from those of any other chronic interstitial lung disease. Progressively worsening dyspnea appears 10 to 20 years after exposure. It is usually accompanied by cough and production of sputum. The disease may remain static or progress to congestive heart failure, cor pulmonale, and death. Pleural plaques are usually asymptomatic and are detected on radiographs as circumscribed calcific densities. # People exposed to asbestos have a markedly increased risk of developing lung carcinoma and malignant mesothelioma. The risk for developing lung carcinoma is increased about 5-fold for asbestos workers, while the relative risk for mesothelioma, normally a very rare tumor (2-17 cases per 1 million individuals), is more than 1000 times greater. Concomitant cigarette smoking greatly increases the risk for lung carcinoma but not for mesothelioma. Lung or pleural cancer associated with asbestos exposure carries a particularly poor prognosis. # Drug- and Radiation-Induced Pulmonary Disease Drugs causes a variety of acute and chronic alterations of lung structure and function. For example, bleomycin, an anticancer agent, causes pneumonitis and interstitial fibrosis through direct toxic effects and by stimulating the influx of inflammatory cells into the alveoli. Amiodarone, an antiarrhythmic agent, is also associated with pneumonitis and fibrosis. Radiation pneumonitis is a well-known complication of irradiation of pulmonary and other thoracic tumors. Acute radiation pneumonitis, which typically occurs 1 to 6 months after therapy in as many as 20% of patients, is manifested by fever, dyspnea out of proportion to the volume of irradiated lung, pleural effusion, and pulmonary infiltrates in the irradiated lung bed. These signs and symptoms may resolve with corticosteroid therapy or progress to chronic radiation pneumonitis, associated with pulmonary fibrosis.