Diffuse Parenchymal Lung Diseases Associated with Known Etiologic Agents

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Diffuse Parenchymal Lung Diseases Associated with Known Etiologic Agents



This chapter focuses on several of the major categories of diffuse parenchymal (interstitial) lung disease for which an etiologic agent has been identified. The general principles discussed in Chapter 9 apply to most of these conditions, and the features emphasized here are those peculiar to or characteristic of each cause. Considering the vast number of diffuse parenchymal lung diseases, this chapter only scratches the surface of information available. When a physician is confronted with a patient having a particular type of diffuse parenchymal lung disease, it is best to relearn the details of the disease at that time.



Diseases Caused by Inhaled Inorganic Dusts


Many types of diffuse parenchymal lung disease are caused by inhalation of inorganic dusts; the term pneumoconiosis is used for these conditions. Examples of the many responsible agents include silica, asbestos, coal, talc, mica, aluminum, and beryllium. In most cases, contact has occurred for a prolonged time as a result of occupational exposure. In some of these diseases, the parenchymal process progresses even in the absence of continued exposure.


For an inhaled inorganic dust to initiate injury to the lung parenchyma, it must be deposited at an appropriate area of the lower respiratory tract. If particle size is too large or too small, deposition tends to be in the upper airway or in the larger airways of the tracheobronchial tree. Particles with a diameter of approximately 0.5 to 5 µm are most likely to deposit in the respiratory bronchioles or the alveoli.



Particles with a diameter of 0.5 to 5 µm are most likely to be deposited in respiratory bronchioles or alveoli.


No effective treatment is available for parenchymal lung disease caused by most inhaled inorganic dusts. Therefore, the important issues facing physicians are recognition and prevention of these disorders. Total avoidance of exposure is the optimal form of prevention, but when exposure is necessary, appropriate precautions with effective masks or respirators are essential.


Four types of pneumoconiosis are considered here: silicosis, coal worker’s pneumoconiosis, asbestosis, and berylliosis. For information about the numerous other agents, consult the more detailed references at the end of this chapter.



Silicosis


Silicosis is the diffuse parenchymal lung disease resulting from exposure to silica (silicon dioxide). Of several crystalline forms of silica, quartz is the one most frequently encountered, usually as a component of rock or sand. Persons at risk include sandblasters, rock miners, quarry workers, and stonecutters. In most cases, development of disease requires at least 20 years of exposure. However, with particularly heavy doses of inhaled silica, as are found in sandblasters, much shorter periods are sufficient.


Although the pathogenesis of silicosis is not known with certainty, theories have focused on the potential toxicity of silica for macrophages. Silica particles in the lower respiratory tract are phagocytosed by alveolar macrophages. Freshly cut silica particles are more pathogenic than older particles. This property is thought to be due to the increased redox potential of the fresh surface, which is highly reactive. After engulfing the silica particle, the macrophage is activated and releases inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin-1, and arachidonic acid metabolites. Phagocytosis of silica particles leads to apoptotic cell death, and toxic silica particles are released that are capable of repeating the process after they are reingested by other macrophages. With their activation and destruction, the macrophages release chemical mediators that initiate or perpetuate an alveolitis, eventually leading to development of fibrosis. Pathologically, the inflammatory process initially is localized around the respiratory bronchioles but eventually becomes more diffuse throughout the parenchyma. The ongoing inflammatory process causes scarring and results in characteristic acellular nodules called silicotic nodules that are composed of connective tissue (Fig. 10-1). At first the nodules are small and discrete. With disease progression they become larger and may coalesce. Silicotic nodules are believed to be areas in which the cycle of macrophage ingestion, activation, destruction, and release of the toxic silica particles occurs.




The pulmonary effects of silica may be related to a toxic effect on alveolar macrophages.


The most common radiographic appearance of silicosis is notable for small, rounded opacities or nodules. This pattern is described as simple chronic silicosis. Uncommonly, the nodules become larger and coalescent, in which case the pneumoconiosis is called complicated; the term progressive massive fibrosis has also been used (Fig. 10-2). As a general rule, in patients with silicosis the upper lung zones are affected more heavily than the lower zones. Enlargement of the hilar lymph nodes, which frequently calcify, may be seen.



In addition to the potential problem of progressive pulmonary involvement and eventual respiratory failure, abnormal immune regulation is associated with silicosis. Patients are at increased risk for certain autoimmune diseases including rheumatoid arthritis and systemic sclerosis. In addition, patients with silicosis are particularly susceptible to infections with mycobacteria, perhaps because of impaired macrophage function. The specific organisms may be either Mycobacterium tuberculosis, the etiologic agent for tuberculosis, or other species of mycobacteria, often called atypical or nontuberculous mycobacteria (see Chapter 24).



Silicosis is associated with immune dysregulation and is a predisposing factor for secondary infections by mycobacteria.



Coal Worker’s Pneumoconiosis


Individuals who have worked as part of the coal mining process and have been exposed to large amounts of coal dust are at risk for development of coal worker’s pneumoconiosis (CWP). In comparison with silica, coal dust is a less fibrogenic material, and the tissue reaction is much less marked for equivalent amounts of dust deposited in the lungs.



Tissue reaction to inhaled coal dust is much less than that to silica.


The pathologic hallmark of CWP is the coal macule, which is a focal collection of coal dust surrounded by relatively little cellular infiltration or fibrosis (Fig. 10-3). The initial lesions tend to be distributed primarily around respiratory bronchioles. Small associated regions of emphysema, termed focal emphysema, may be seen.



As with silicosis, the disease is often separated into simple and complicated forms. In simple CWP, the chest radiograph consists of relatively small and discrete densities that usually are more nodular than linear. In this phase of the disease, patients have few symptoms, and pulmonary function usually is relatively preserved. In later stages of the disease, to which only a small minority of individuals progress, chest radiographic findings and clinical symptoms are more pronounced. With extensive disease and coalescent opacities on chest radiographs, patients are said to have complicated CWP, also called progressive massive fibrosis.


Why complicated disease develops in some patients with CWP is not clear. At one time, it was speculated that patients with progressive massive fibrosis had also been exposed to toxic amounts of silica and that the simultaneous silica exposure was responsible for most of the fibrotic process. However, although some patients do have a mixed form of pneumoconiosis from both coal dust and silica exposure, progressive massive fibrosis can result from coal dust in the absence of concomitant exposure to silica. More recently, genetic polymorphisms have been identified that may help explain the different clinical responses to inhalational exposures.



Symptoms and pulmonary function changes in coal worker’s pneumoconiosis (CWP) occur primarily in patients with progressive massive fibrosis.



Asbestosis


Asbestos has been widely used because of its thermal and fire resistance. It is a fibrous derivative of silica, termed a fibrous silicate. It is a naturally occurring mineral that, because of its long narrow shape, can be woven into cloth. Among the health hazards it presents are the development of diffuse interstitial fibrosis, benign pleural plaques and effusions, and the potential for inducing several types of neoplasm, particularly bronchogenic carcinoma and mesothelioma. These latter problems are discussed in Chapters 15, 20, and 21. The term asbestosis should be reserved for the diffuse parenchymal lung disease that occurs as a result of asbestos exposure.


Asbestos still presents a major health issue in many developing countries where the mineral is mined and used in industrial applications. Individuals at risk for development of asbestosis include asbestos miners; insulation, shipyard, and construction workers; and persons who have been exposed by working with brake linings. Even though the health hazards of asbestos are well recognized and use of asbestos has been curtailed in industrialized countries, workers still may be exposed in the course of remodeling or reinsulating pipes or buildings in which asbestos had been used. The duration of exposure necessary for development of asbestosis usually is more than 10 to 20 years but can vary depending on the intensity of the exposure.


One theory for the pathogenesis of asbestosis suggests that asbestos fibers activate macrophages and pulmonary epithelial cells, inducing the release of mediators that attract other inflammatory cells, including neutrophils, lymphocytes, and more alveolar macrophages. Unlike silica, asbestos probably is not cytotoxic to macrophages. That is, it does not seem to destroy or “kill” macrophages in the way that silica does. The mechanism of the often significant fibrotic reaction that occurs with asbestos may be related to the release of mediators from macrophages (e.g., transforming growth factor [TGF]-β, TNF-α, fibronectin, insulin-like growth factor [IGF]-1, and platelet-derived growth factor) that can promote fibroblast recruitment and replication. An area of active research involves studying the effects of asbestos fibers on initiating abnormalities in alveolar epithelial cell apoptosis and proliferation. Genetic polymorphisms in TGF-β and TNF-α have been associated with increased susceptibility to the toxic effects of asbestos.


The earliest microscopic lesions appear around respiratory bronchioles, with inflammation that progresses to peribronchiolar fibrosis. The fibrosis subsequently becomes more generalized throughout the alveolar walls and can become quite marked. Areas of the lung that are heavily involved by the fibrotic process include the lung bases and subpleural regions.


A characteristic finding of asbestos exposure is the ferruginous body, a rod-shaped body with clubbed ends (Fig. 10-4) that appears yellow-brown in stained tissue. Ferruginous bodies represent asbestos fibers that have been coated by macrophages with an iron-protein complex. Although large numbers of these structures are commonly seen by light microscopy in patients with asbestosis, not all such coated fibers are asbestos, and ferruginous bodies may be seen even in the absence of parenchymal lung disease. Uncoated asbestos fibers, which are long and narrow, cannot be seen by light microscopy and require electron microscopy for detection.


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Jun 12, 2016 | Posted by in RESPIRATORY | Comments Off on Diffuse Parenchymal Lung Diseases Associated with Known Etiologic Agents

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