Pneumoconiosis is characterized by an inhalation of foreign nonliving material in the widest sense but is usually restricted to inorganic matter. Inhalation causes a tissue reaction, which can be any kind of pneumonia, granulomatosis, or similar. Primarily when thinking about pneumoconiosis, silicosis and asbestosis will immediately come into one’s mind; however, there are many more agents causing pulmonary diseases. As in many other diseases in all kinds of pneumoconiosis, there is a dose-effect relationship: this means there is a threshold dose required to induce disease (amount of a mineral) and duration of exposure. In addition, the dimension of the particles is important too: particles larger than 10 μm are deposited in the larger airways; particles below 2–5 μm will reach the alveolar periphery. But there is another factor, aerodynamic diameter: particles are within the airstream and will orient themselves along the axis of the airflow; therefore, asbestos fibers although 100–200 μm in length are less than 5 μm thick, which means they are oriented within the airstream and might reach small bronchioles before being trapped at bifurcations. Another quality of inhaled mineral dust is durability: some metals are easily dissolved in extracellular fluids and can be absorbed and removed by macrophages. Other minerals such as quartz and asbestos fibers are long lasting and resist degradation by macrophages for months. Finally also the chemical composition plays a role: highly toxic compounds will cause acute injury to the lung, whereas other minerals cause injury only in huge quantities, as example for both is chromates versus titanium oxides. On the other hand, our lung has developed many clearance and defense mechanisms during evolution. We all inhale some amount of quartz, but usually do not develop silicosis, because quartz is cleared. There are several mechanisms: The evolutionary oldest mechanism is the mucus escalator system; mucus is produced by goblet cells and moved toward the larynx. Particles deposited within the mucus are transported with it and expectorated or coughed out. Another evolutionary old mechanism is clearance by macrophages; these cells of the innate immune system patrol through the lungs, phagocytose, and degrade foreign particles, thus preventing toxic injury. Finally there is also a chemical defense system. The epithelial cells of the airways and the pneumocytes produce two different enzyme systems: oxidizing enzymes such as the cytochromes and detoxifying enzymes such as the (de)aminidases, glutathione synthases and glutathione transferases, etc. [1–5]. All these form together an efficient defense against inhaled mineral particles.

There are several tissue reactions in those cases when the amount of inhaled particles and their toxicity and durability overcome the clearance mechanisms (Table 13.1).

Quartz oxides induce silicosis, the major component being SiO₂. The mechanism on how silica oxides cause silicosis is not entirely clear; however, most probably inflammation is started by depolarization of biological membranes caused by quartz. Quartz crystals phagocytosed by macrophages act by their piezoelectric effect and cause depolarization of the phagolysosomes and thus release toxic enzymes into the cytoplasm, subsequently causing cell death [6]. These enzymes then will cause oxygen radical production and activation of NFκB, TNFα, and cyclooxygenase II and contribute to the destruction of pneumocytes and alveolar walls including basement membranes [7–9]. The first tissue reaction in silicosis is a granulomatous reaction with histiocytes, in very early stages even foreign body giant cells. In acute silicosis with high-dose inhalation, a simple macrophage reaction is also seen (Fig. 13.1). In rare cases, silicoproteinosis can be caused by high-dose inhalation, especially if amorphous silica is inhaled (Fig. 13.2). TGF-β seems to be the major mediator of fibrosis and is produced by hyperplastic pneumocytes type II as well as by fibroblasts and macrophages at the periphery of silicotic granulomas. The hyperplastic pneumocytes appear to be the predominant sites of production and secretion of TGF-β1 and mediate the production of extracellular matrix [10]. These granulomas represent the early stages of silicosis and fulfill the criteria for compensation by state agencies. Later on these granulomas undergo hyalinization and form the typical hyaline granulomas of full-blown silicosis (Fig. 13.3). By polarized light quartz is seen as white birefringent crystals, usually 7 μm in length and less 1 μm in diameter (Fig. 13.4). Usually nodules coalesce and form large aggregates. In the center necrosis can occur, most probably by ischemia.

Silica degradation takes several months, and usually silica crystals are constantly released from the granuloma border and subsequently will start the destructive process again. So even if the patient is withdrawn from the exposure, silicosis will progress although less rapidly. Over time the granulomas undergo fibrosis, forming large scars. This in turn will cause tractions of the bronchi and bronchiectasis. If bronchi are within the fibrotic area, they can even be obliterated.

The upper lobes are usually more severely affected by silicosis, and the hilar lymph nodes can appear black, firm, and packed together. The distribution pattern of silicosis can be best demonstrated by HRCT scan or by whole lung sections on paper mounts (Fig. 13.5).

Occupational exposure: In former days, the majority of patients presenting with silicosis were found within coal mines (e.g., the Rhine-Ruhr area in Germany and the coal mines in Poland) due to the contamination of hard coal with high proportion of silicates (up to 35 %). Other exposures occurred in tunnel construction, brick production, sandblasting, masonry, founding, ceramic fabrication, gold mining (South African mines), and dental laboratories [11–13]. Silicon oxides come in two forms, crystalline (quartz, tridymite, cristobalite) and amorphous (diatomite). For many years, amorphous silica was regarded as non-fibrogenic. However, experimental work has shown that amorphous silica is as dangerous as crystalline [14].

Outcome and secondary changes: Bronchiectasis and bronchial obstruction will cause severe emphysema; pulmonary blood vessels usually undergo fibrosis and obliteration. Especially the small arteries and capillaries are lost. The whole diameter of the peripheral capillary system can be reduced by more than one third. Emphysema formation results in hypoxia, sclerosis of pulmonary arteries will cause pulmonary arterial hypertension, and both will together act on right ventricular hypertrophy followed by right ventricular failure.

Silica/quartz has been regarded as fibrogenic but not cancerous. This dogma has also been refuted by several studies [11, 15–18].

Different metals can cause lung diseases. Some of these we will not discuss here, as chronic allergic metal disease, which is characterized by non-necrotizing epithelioid cell granulomas (beryllium, zirconium). Others cause a classical pneumoconiosis, such as hard metal, aluminum, and zinc. Different types of metals can be detected by electron microscopy using devices for element detection. One problem in these investigations is that several of these metals are easily dissolved by the fixation and dehydration in fluid and leach out of the tissue. Another option is using “old-style” chemical reactions used for the analysis of complex compounds. This can be done using solvents to leach out the materials of interest followed by a chemical reaction with dyes, which turn color, if the element is present. Many of these chemical reactions can also be performed on tissue sections. However, this all is only possible for elements, which normally do not occur within human tissues.