A variety of CT patterns has been described in hypersensitivity pneumonitis (Box 8.3).^{123.124. and 125.}

The nodules of hypersensitivity pneumonitis are round, poorly defined, and less than 5 mm in diameter (Figs 8.14 and 8.16). ¹¹⁸ They are typically centrilobular¹²⁶ and profuse throughout the lung but a mid- to lower lung zone predominance has been variably reported. ¹²⁷ In contrast to the centrilobular nodules of silicosis and other inhalational diseases, they are usually of ground-glass attenuation rather than of soft tissue attenuation. Profuse nodules of this type can be diagnostic of hypersensitivity pneumonitis in the correct clinical context. Although the nodules are centrilobular, a tree-in-bud pattern indicative of cellular bronchiolitis is quite uncommon.^{126.127. and 128.} The nodules usually regress with removal from exposure.^{126. and 129.}

Ground-glass opacification in hypersensitivity pneumonitis (see Fig. 8.12) may be patchy or diffuse,^{125. and 127.} and it may resolve with removal from exposure. ¹²⁶ It is usually associated with restrictive physiology and impaired gas exchange on pulmonary function testing. ¹³⁰ Ground-glass opacification is frequently found in association with other CT abnormalities such as centrilobular nodules, lobular decreased attenuation, or air-trapping (Fig. 8.12). Lung cysts may be seen in about 10% of cases of subacute hypersensitivity pneumonitis, but are usually sparse. ¹³¹ In chronic hypersensitivity pneumonitis, fibrosis is signified by irregular linear opacities, traction bronchiectasis, lobar volume loss, and honeycombing (Fig. 8.17).^{123. and 132.} This abnormality may predominate in upper, mid- or lower lung zones, ¹²⁷ but often spares the extreme lung bases.^{133. and 134.} In the axial plane, the fibrotic changes are randomly distributed but a subpleural predominance has been described in some patients. ¹²⁷ Conversely upper lobe fibrosis may occasionally be somewhat bronchocentric. Honeycombing (Fig. 8.18) may be found in up to 60% of cases.^{97.126. and 133.} The presence of CT signs of fibrosis in patients with hypersensitivity pneumonitis correlates with histologic evidence of lung fibrosis, ¹³² and predicts poorer survival. Hanak et al. ¹³⁵ followed up 26 patients with hypersensitivity pneumonitis who had CT signs of lung fibrosis and found that 11 had died, compared with 1 of 43 without evidence of fibrosis.

A mosaic attenuation pattern is common in hypersensitivity pneumonitis (Figs 8.12, 8.18 and 8.19), found in 80–90% of patients.^{130.133. and 136.} In hypersensitivity pneumonitis, the mosaic pattern is usually due to a combination of patchy areas of ground-glass attenuation and lobular areas of decreased attenuation and vascularity due to air-trapping. When lobular decreased attenuation involves several lobules in more than four lobes, hypersensitivity pneumonitis is by far the most likely diagnosis. ¹³³ Air-trapping on expiratory imaging is seen in many cases of hypersensitivity pneumonitis (Fig. 8.19), ¹³⁶ and may be the predominant or only feature. HRCT evidence of air-trapping correlates with evidence of obstruction on pulmonary function testing.^{130. and 137.} The air-trapping and mosaic attenuation are presumed to be due to bronchiolitis. ¹²³

Fibrobullous lung destruction is (unlike in sarcoidosis) extremely unusual (Fig. 8.20). Radiographic evidence of emphysema in patients with chronic hypersensitivity pneumonitis was first noted by Barbee et al. ⁸⁶ in 1968. Remy-Jardin et al. ¹²⁶ noted emphysematous changes on HRCT in 50% of patients with chronic bird fancier’s hypersensitivity pneumonitis (Fig. 8.21). Both Lalancette et al. ¹⁰⁹ and Cormier et al. ¹³⁸ reported that emphysema occurred more commonly than fibrosis in chronic farmer’s lung. Another study showed an increased prevalence of emphysema in farmer’s lung patients compared with control farmers matched for age, sex, and smoking status. ¹²⁴ In that study, 13 of the 20 farmer’s lung patients with emphysema were never smokers. Up to 50% of patients with hypersensitivity pneumonitis have mediastinal lymphadenopathy on CT, ¹³⁹ but the enlarged nodes are almost always smaller than 2 cm in short axis. ¹³⁹ Lymph node enlargement is therefore usually not visible on the chest radiograph.

As with other types of fibrotic lung disease, acute exacerbations of chronic hypersensitivity pneumonitis may occur, and are characterized by extensive new ground-glass opacities, sometimes with focal areas of consolidation, superimposed on a fibrotic pattern. ¹⁴⁰ The CT finding of consolidation is otherwise quite uncommon in hypersensitivity pneumonitis.

The imaging findings in hypersensitivity pneumonitis do not necessarily correlate with the duration of symptoms. Centrilobular nodules, ground-glass attenuation, and mosaic attenuation may all be found at any phase of the disease, and may be the sole finding even in patients with clinically chronic hypersensitivity pneumonitis. Findings of fibrosis or emphysema are usually found only in chronic hypersensitivity pneumonitis.

The differential diagnosis of hypersensitivity depends on the imaging findings. Profuse poorly defined nodules of ground-glass attenuation are virtually pathognomonic of hypersensitivity pneumonitis (Figs 8.14 and 8.16). The differential diagnosis may include smoking-related RB but in this condition the nodules are usually more patchy and sparse. Other diagnostic considerations should include pulmonary hemorrhage and metastatic pulmonary calcification. If the nodules are of soft tissue attenuation, sarcoidosis, chronic beryllium disease, or pneumoconiosis would be more likely than hypersensitivity pneumonitis. A patchy or unilateral distribution of nodules should suggest infection. ¹²⁸

When ground-glass attenuation is present as the only sign of hypersensitivity pneumonitis, it may be indistinguishable from other conditions characterized by ground-glass attenuation such as viral infection, organizing pneumonia, DIP, or NSIP. Associated lobular hyperlucency should suggest the diagnosis of hypersensitivity pneumonitis, though the combination of ground-glass attenuation and hyperlucency may also be found in sarcoidosis.

Patients with chronic hypersensitivity pneumonitis may exhibit a histologic and imaging pattern of NSIP (Fig. 8.17) or UIP (Fig. 8.18). Hypersensitivity pneumonitis should always be considered in the differential diagnosis of NSIP¹¹⁵ and of UIP. ¹³⁴ Imaging features which favor hypersensitivity pneumonitis over IPF or NSIP include lack of lower lung predominance, presence of centrilobular nodules, ground-glass abnormality or lobular air-trapping, and absence of honeycombing.^{133. and 134.} However, these imaging features permit a confident distinction of chronic hypersensitivity pneumonitis from NSIP or UIP in only about 50% of cases. Therefore, hypersensitivity pneumonitis should always be considered in fibrotic lung disease, even when the imaging features are typical of NSIP or UIP.

Silica dust particles of appropriately small size are deposited on the alveolar walls and ingested by macrophages. They may enter the pulmonary lymphatics, or they may be transported to bronchioles for mucociliary clearance. The silica particle is directly cytotoxic to the macrophage. The dying macrophages induce fibrosis by releasing oxidants, proinflammatory cytokines, and stimulants of fibroblast proliferation. ¹⁵⁴

The basic histologic lesion of silicosis is the hyalinized nodule. These nodules are usually more prominent in the upper zones and lie close to the bronchioles, small vessels, and lymphatics. They consist of concentric layers of collagen containing silica particles surrounded by a fibrous capsule. The outer zone is made up of irregularly dispersed connective tissue that also contains crystalline silica. The host response to this peripheral silica results in enlargement and conglomeration of nodules. The fibrosis seen with silicosis is both more abundant and more collagenous than that seen with other mineral dusts, such as coal. Silica-laden macrophages that reach the hilar and mediastinal nodes form granuloma-like lesions in the nodes.

Silicosis is often complicated by massive fibrotic lesions that are the result of the conglomeration of nodules matted together by fibrosis. These masses, which contain obliterated blood vessels and bronchi, may cavitate. The pulmonary macrophage, important in the granulomatous response to the infection, is damaged by silica particles rendering the silicotic individual more susceptible to mycobacterial or fungal infection. ¹⁵⁵

The earliest radiographic changes of silicosis are 1–3 mm round, well-defined nodules, especially in the posterior portions of the upper two-thirds of the lungs (Fig. 8.23).^{156. and 157.} A lower lung predominant reticular pattern may also be seen, either alone or in combination with the nodules. As the process advances, the nodules increase in size and number and become more widespread, involving all zones. Usually the nodulation is symmetric. Sometimes the nodules are calcified.

On CT scanning, the micronodules are usually centrilobular and perilymphatic (Fig. 8.24).^{158.159. and 160.} As the disease evolves, there is spread anteriorly and inferiorly, although the upper zone preponderance is usually maintained. The upper lung preponderance is thought to be due to poor lymphatic clearance from the upper lobes. ¹⁶¹ Subpleural nodules may cluster to form ‘pseudoplaques’ (Fig. 8.25). ¹⁶² Larger nodules may also be seen, and may calcify. Interlobular septal thickening may be present. Not surprisingly, CT is clearly more sensitive than the chest radiograph for detection of nodules and of early conglomerate fibrosis. In a study of 44 silica exposed workers, CT identified small nodules in four workers who did not have nodules visible on chest radiograph, and identified PMF in 33 workers, compared with only 23 on chest radiograph. ¹⁶³ CT scores for nodules and emphysema correlate with physiologic impairment.^{163. and 164.} Interobserver agreement for the presence of nodules is substantially higher for CT than for chest radiograph (kappa value 0.84 compared with 0.54). ¹⁶⁰ CT can objectively quantify the extent of emphysema and of lung nodules, and yields significant correlations with the level of physiologic impairment. ¹⁶⁴

The obstructive component of physiologic impairment in silicosis has usually been attributed to emphysema. However, a study using paired inspiratory and expiratory CT in 34 workers with silicosis showed that air-trapping was in fact the most common finding in these individuals, and correlated quite strongly with a decreased forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio. ¹⁶⁵ This study suggests that expiratory CT should be part of the routine CT evaluation of silica-exposed workers.

Hilar and mediastinal lymph node enlargement is quite common in silicosis. Calcification, sometimes of the eggshell type, may be seen in the nodes, either on chest radiograph (Fig. 8.26) or on CT. ¹⁶⁶ In a study of 41 subjects with silicosis, lymph node classification was most commonly uniform or speckled; central, eccentric, or eggshell calcification was quite uncommon. The measured attenuation of lymph nodes correlated with the presence of PMF, with CT profusion of nodules, and with reduced lung diffusing capacity. ¹⁶⁷

PMF may occur in silicosis or coal worker’s pneumoconiosis. Synonyms include complicated pneumoconiosis or conglomerate pneumoconiosis. This entity is defined radiographically by the presence of nodules greater than 1 cm in diameter. Recognition of PMF is important because it indicates that the patient is likely to be symptomatic and physiologically impaired. Typically, PMF starts as a round or oval mass near the periphery of the lung (Fig. 8.25), often with a well-defined lateral border that parallels the lateral chest wall. Lateral view confirms the posterior location and the oval appearance of the conglomerate mass (Fig. 8.27).

Masses of PMF, as the name implies, enlarge with time. The rate of growth is very slow, usually occurring over years. As the nodules coalesce and the upper lobes contract, the hila retract and compensatory emphysema occurs in the lower lobes. Apical pleural thickening is frequently seen. Some PMF lesions migrate medially toward the hilum, leaving a rim of peripheral cicatricial emphysema (Fig. 8.28). The migration is slow, taking 10 or more years to reach the hilum. Cavitation may be visible, and the cavities may empty and fill over a period of time. ¹⁶⁸ Noncavitary large PMF lesions often show irregular low-attenuation regions on CT indicative of avascular necrosis. The presence of cavitation should always raise the suspicion of mycobacterial (including nontuberculous tuberculosis) superinfection. In 44 patients with silicosis and PMF studied by CT, 89% were located in the superior and posterior thirds of the lung. ¹⁶⁹ Air bronchograms were seen within the masses in 70%, and calcifications in 64%. A study of 25 Brazilian sandblasters with PMF yielded very similar findings. ¹⁷⁰

Since PMF is frequently bilateral, relatively symmetric, and accompanied by widespread nodules in the remainder of the lungs (Fig. 8.29), the diagnosis is rarely in doubt. There are cases, however, where the mass is completely or predominantly unilateral (Fig. 8.30) and background nodules may be minimal or absent. In such cases the differential diagnosis from lung carcinoma becomes particularly important. Features that favor the diagnosis of PMF include an indolent growth rate, oval or lenticular shape, location in an upper lobe close to and parallel to the major fissure, well-defined outer margin paralleling the chest wall, small irregular calcifications, upper lobe volume loss, and peripheral emphysema. 18-Fluorodeoxyglucose on PET-CT is of little assistance in resolving the differential diagnosis between lung cancer and silicosis, because increased uptake of this agent may be seen in lesions of PMF and in associated mediastinal lymph nodes (Fig. 8.31).^{171.172. and 173.} Chong et al. ¹⁷³ suggested that the presence of high signal on T2-weighted magnetic resonance imaging (MRI), and peripheral enhancement following gadolinium contrast administration, may be helpful in distinguishing lung cancer from PMF.

In addition to lung cancer, sarcoidosis must be considered in the imaging differential diagnosis of PMF, as the radiographic and CT features of lymphadenopathy, predominantly perilymphatic nodules and conglomerate fibrosis, in this condition may be very similar.

While chronic simple silicosis refers to the development of silicosis between 10 and 30 years after exposure, accelerated silicosis refers to the development of silicosis within 10 years of exposure (usually related to more intense exposure). ¹⁷⁴ The radiographic appearance of this entity is similar to that of chronic simple silicosis. However, workers with accelerated silicosis are at high risk for the development of complications such as PMF. ¹⁷⁵ Intense exposure to silica dust, which may occur in sandblasters, may result in lung damage after only weeks or months, called acute silicosis or silicoproteinosis. The dominant histologic feature is the presence of an alveolar proteinaceous exudate, similar to that found in pulmonary alveolar proteinosis, hence the term ‘acute silicoproteinosis’.^{176. and 177.} Death may ensue within 1–3 years.

On radiographic examination of patients with silicoproteinosis there is widespread alveolar opacity that progresses over a period of months. ¹⁷⁸ The opacity is quite symmetric, but central and upper zone predominance is frequent (Fig. 8.32). Air bronchograms may be noted, and contraction of the lungs may be minimal at first, suggesting consolidation of the lungs. Hilar and mediastinal adenopathy may be seen, but the hila are often obscured by the parenchymal opacities. Peripheral air-trapping, bulla formation, lung volume loss, and distortion of mediastinal structures all indicate increasing fibrosis. Pneumothorax may occur. Silicoproteinosis may present with recurrent episodes of apparent pneumonia. ¹⁷⁹

In a recent study of 13 patients (all sandblasters) with silicoproteinosis, the workers had been exposed for a median of 3.2 years, and presented with rapidly progressive respiratory symptoms. ¹⁸⁰ Bilateral airspace consolidation was the most frequent finding on CT, found in 12 of 13 patients, and usually without zonal predominance. Foci of calcification were found within the areas of consolidation in 10 patients: this finding is unusual in other causes of consolidation and should strongly suggest the diagnosis. In the only patient without consolidation, the CT showed diffuse ground-glass abnormality and small centrilobular nodules. Centrilobular nodules were seen in 11 of 13 patients, and were usually diffuse. Confluent nodules were present in nine cases. Ground-glass opacity was seen in eight patients, but the crazy-paving pattern typical of pulmonary alveolar proteinosis was not identified in any case. However, a crazy-paving pattern was illustrated in some other reported cases.141. ^{and 173.} Calcified lymph nodes were present in 11 patients. Mild pleural thickening or pleural effusion was seen in 11 patients. Tracheal dilatation was present nine cases.

The relative risk of lung cancer in silica-exposed individuals ranges from 1.3 to 6.9, depending on the population, ¹⁷⁹ but some of this excess risk is accounted for by cigarette smoking. Analysis is also complicated by the carcinogenic effect of radon gas exposure in miners. Nevertheless, both the American Thoracic Society¹⁷⁹ and the International Agency for Research on Cancer¹⁸¹ have issued statements indicating that silica is a probable carcinogen and cause of lung cancer. It has not been established whether the risk is related to silica itself or to the pulmonary fibrosis induced by the silica.

Chronic bronchitis is probably the most common complication of silica exposure, often associated with airway obstruction. It has no radiographic manifestations, apart from airway wall thickening. Broncholithiasis with hemoptysis has been described in a patient with silicosis. ¹⁸² Silica exposure may be associated with emphysema (see Fig. 8.25). However, as with lung cancer, the confounding effect of cigarette smoking complicates analysis. Nonsmokers exposed to silica may develop emphysema, ¹⁸³ particularly if they also have silicosis, ¹⁸⁴ but the extent and physiologic significance of this emphysema are disputed. ¹⁸⁵ It is clear, however, that, in patients with simple silicosis, the degree of impairment of pulmonary function is more closely related to the presence and severity of emphysema on CT than to the profusion of nodules.^{157. and 186.} Most emphysema seen in association with silicosis is centrilobular, but cicatricial emphysema commonly occurs in association with PMF (Fig. 8.25).

Inhalation of silica predisposes to mycobacterial infection, classically with Mycobacterium tuberculosis, but infection with Mycobacterium kansasii, Mycobacterium avium complex, and other uncommon organisms has also been noted^{155. and 187.} (Fig. 8.33). In one study, the relative risk of tuberculosis in workers with chronic silicosis was increased threefold compared with a control group. ¹⁷⁹ The risk of mycobacterial infection is even greater in those with accelerated or acute silicosis, and in those with PMF. Mycobacterial infection in people with silicosis may be pulmonary or extrapulmonary. Pulmonary mycobacterial infection should always be suspected when cavitation, consolidation, or new nodules develop in a patient with silicosis (Fig. 8.33). ¹⁸⁷

Silica workers have an increased risk of chronic interstitial pneumonia.^{188. and 189.} The most common histologic pattern is UIP (Fig. 8.34). ¹⁹⁰ Arakawa et al. ¹⁹⁰ reviewed the CT scans of 243 workers with silicosis or mixed dust pneumoconiosis, and found a CT pattern of chronic interstitial pneumonia in 28 (11%). When compared with a group of patients with idiopathic pulmonary fibrosis, the overall extent of fibrosis and honeycombing was similar, but the extent of reticular and ground-glass abnormality, and of traction bronchiectasis, was less in those with pneumoconiosis, while the extent of nodules, emphysema, and subpleural homogeneous attenuation (shown histologically to represent confluent silicotic nodules) was greater. In a retrospective analysis of 14 patients with this form of chronic interstitial pneumonia, followed by CT for a median of 15.4 years, the extent and coarseness of fibrosis showed linear progression in 13 patients, and honeycombing developed in all patients over a median of 12.1 years. ¹⁹¹

Silica-exposed individuals are also at increased risk of scleroderma^{192. and 193.} and perhaps of other collagen vascular diseases including rheumatoid arthritis, ¹⁷⁹ dermatomyositis–polymyositis, ¹⁹⁴ and systemic lupus erythematosus. ¹⁹⁵ The prevalence of pleural abnormality in silicosis has been underemphasized: one report emphasizes that silicosis is associated with unexplained pleural effusions in 11% and pleural thickening in 58% of patients¹⁹⁶ (Fig. 8.25). Rounded atelectasis may also be seen.^{197. and 198.}

It has been stated that simple coal worker’s pneumoconiosis is symptom free. ²⁰³ However, as with silica workers, coal miners commonly have symptoms of bronchitis and emphysema, features that are excluded from the definition of pneumoconiosis, but are responsible for significant symptoms and physiologic impairment.

PMF category A (nodules less than 5 cm) appears not to cause symptoms or signs. Categories B and C may be associated with respiratory disability and deterioration in ventilatory function tests. ²⁰³ Cough and sputum sometimes occur. Hemoptysis is rare. Cavitation of a PMF lesion may be associated with expectoration of jet-black sputum (melanoptysis). When this occurs, CT or MRI may show a fluid–fluid level within the cavity, and may show rim enhancement. ²¹⁰

The radiographic and CT signs of coal worker’s pneumoconiosis are usually indistinguishable from those described above for silicosis (Figs 8.29, 8.30, 8.35 and 8.36). Statistically, the main differences between coal worker’s pneumoconiosis and silicosis are that the nodules in coal worker’s pneumoconiosis tend to be smaller, and that silicosis is more likely to progress to PMF. PMF is uncommon in coal workers with less than 20 years’ experience in and around the mines. ²¹¹ Its appearance in coal workers is identical to that seen in silicosis (Fig. 8.27).

A minority (perhaps 10–20%) of coal miners develop diffuse lung fibrosis, characterized on the chest radiograph by small irregular opacities^{212. and 213.} (Fig. 8.37). These irregular opacities correlate better than rounded opacities with the extent of physiologic impairment. ²¹⁴ On CT, this entity is characterized by reticular abnormality often associated with honeycombing, similar to UIP or NSIP.^{215. and 216.} This abnormality may or may not be associated with pneumoconiotic nodules. This pattern of diffuse interstitial fibrosis appears to be associated with a high prevalence of lung cancer, preferentially occurring in areas of lung fibrosis. ²¹⁶ Other CT findings in coal worker’s pneumoconiosis may include bronchiectasis. ²¹⁷

The chest radiograph reflects the extent and severity of the macules and masses found pathologically, and is therefore a good tool for diagnosing and following the progression of coal worker’s pneumoconiosis.^{156.168.202.218.219.220.221. and 222.} The radiographic findings correlate well with the amount of dust to which the worker was exposed²⁰⁴ and the quantity of dust found in the lungs at postmortem examination. ²²³ However, the correlation between the chest radiograph and lung function is poor, except in patients with large conglomerate masses, ²²⁴ probably because the radiograph substantially underdiagnoses the associated emphysema.^{200. and 206.} The degree of functional disability appears to correlate far better with the severity of emphysema than it does with the presence of macules or PMF.^{157.200.221. and 225.} The etiologic role of smoking in coal worker’s emphysema is controversial. Some studies have shown that coal miners have a degree of emphysema that is excessive even if allowance is made for age and smoking history.^{226. and 227.} This applies particularly to patients with PMF. At lesser degrees of pulmonary involvement, smoking may play a more substantial role in the causation of the emphysema and hence the patient’s symptoms.^{157. and 228.}

Although the pace of progression of coal worker’s pneumoconiosis is usually slow, a subset of workers develop rapidly progressive pneumoconiosis, defined as development of new PMF or increase in profusion of small opacities by more than one subcategory under the ILO classification system in 5 years or less. A recent study found a total of 886 cases of coal worker’s pneumoconiosis among 29 521 workers evaluated between 1996 and 2002. ²²⁹ In a subset of 783 in whom progression could be evaluated, 277 (35%) had rapidly progressive pneumoconiosis. The radiologist should recognize the occurrence of rapidly progressive pneumoconiosis, as it is often a sentinel event, indicating inadequate preventive measures at the worksite. ²²⁹

Benign asbestos-related pleural effusion is one of the less common manifestations of asbestos exposure, but it has the shortest latency period241. ^{and 242.} (Box 8.10). Diagnosis of this condition is sometimes missed because of the transient, often asymptomatic nature of these effusions and the lack of specific markers to indicate their cause. Indeed the diagnosis is one of exclusion and should conform to the following criteria:

In an epidemiologic study by Epler et al., ²⁴¹ the overall incidence of benign pleural effusion was 3.1%, with a 7% incidence among individuals having a heavy occupational exposure and a 0.2% incidence in environmentally exposed individuals. Effusions may be unilateral or bilateral and tend to recur. The amount of fluid is usually small; effusions greater than 500 mL are uncommon. The fluid has the characteristics of an exudate and may be blood tinged. Symptoms include pleuritic pain, fever, and an elevated white blood cell count, but many patients have only mild symptoms or no symptoms at all. Indeed the presence of substantial chest pain should lead to concern for mesothelioma.

Benign pleural effusion is the most common abnormality seen within 10 years of the onset of asbestos exposure. However, it may occur up to 58 years after initial exposure. ²⁴³ No direct causal relationship between benign effusions and the subsequent development of malignant pleural effusion has been postulated, but in one study of 70 cases of malignant mesothelioma, ²⁴⁴ five cases were preceded by what were regarded as successive benign pleural effusions for up to 7 years. In asbestos workers with pleural effusions, the diagnosis of benign effusion should be a diagnosis of exclusion. Mesothelioma should be considered in any patient with a latency longer than 10 years, or in any patient with chest wall pain. In one series of 312 cases of mesothelioma, the latency periods ranged from 14 to 72 years with a mean of 48 years. ²⁴⁵ There appeared to be an inverse relationship between latency and the intensity of exposure; for example, the mean latency period for insulators was 30 years compared with 52 years for domestically exposed women. Benign pleural effusions are associated with the subsequent development of diffuse pleural thickening (Fig. 8.38).^{246. and 247.} McLoud and co-workers²⁴⁸ found that just over 50% of their patients with benign pleural effusions subsequently developed diffuse basal pleural thickening, an association also emphasized by Cookson and associates. ²⁴⁹

Irregular pleural thickening and calcification were first positively related to exposure to asbestos in 1955, ²⁵⁰ and the occurrence of noncalcified, asbestos-induced plaques was first reported in 1967. ²⁵¹ These changes represent the most frequent radiographic manifestation of exposure to asbestos. Although the incidence of pleural plaque formation increases with dose, the elapsed time from initial exposure is a more important factor. ²⁵² Pleural plaques are usually first identified more than 20 or 30 years after the initial asbestos exposure. ²⁵³ Asbestos-induced pleural plaques occur on the parietal pleura, especially over the diaphragm and along the posterolateral chest wall. The apices, the costophrenic sulci, and the mediastinal pleura tend to be spared. The plaques are composed of elevated areas of hyalinized fibrous tissue and frequently lie beneath the ribs. Although usually isolated, they may enlarge, spread, and coalesce. Dystrophic calcification within plaques is common and is more frequent as the plaques age and enlarge. Electron microscopy studies have identified asbestos fibers in the plaques on the parietal pleura, indicating that transpleural migration and assimilation of inhaled asbestos fibers must occur. ²⁵⁴ There is evidence that the widely used, more benign form of asbestos, chrysotile, is particularly associated with this transpleural migration, while the more fibrogenic and carcinogenic amphiboles, crocidolite and amosite, tend to be retained in the lung parenchyma.^{253. and 255.} This may account for the common finding of asbestos-related pleural disease unassociated with parenchymal fibrosis or intrathoracic malignancy.

Population surveys in industrial regions and in asbestos-mining areas have revealed a surprisingly high incidence of pleural plaques even in individuals who have only a remote connection with asbestos.^{256.257. and 258.} Some of these plaques may be due to incidental asbestos exposure, but some ‘plaques’, detected on chest radiograph, may be due to extrapleural fat. In autopsy-based studies of unselected populations, pleural plaques may be found in up to 20% of patients, and a history of asbestos exposure is lacking in most of these,^{259. and 260.} particularly where the plaques are small or unilateral. ²⁶⁰ Such plaques may be due to unrecognized asbestos exposure or to other pleural injury. Pleural plaque formation and calcification have been noted to occur after contact with other nonasbestos fibrous minerals such as erionite in Turkey²⁶¹ and sepiolite in Bulgaria. ²⁶²

On chest radiographs, noncalcified pleural plaques are identified as smooth elevations of the pleura in profile along the chest wall (Fig. 8.39) or over the diaphragm. Plaques are difficult to identify en face unless they are large or calcified. En face plaques are seen as amorphous areas of increased density. They are relatively flat in relation to their width, and the density of the opacity projected over the lungs is therefore less than would be expected for a parenchymal lesion of equivalent size. Furthermore, one margin of the lesion is likely to be indistinct as it smooths off into normal pleura. Plaques are usually multiple and bilateral. Although Hu et al. ²⁶³ reported that pleural plaques detected on chest radiographs were statistically more common on the left, a left-sided predominance was not confirmed in a CT-based study. ²⁶⁴

Calcification in pleural plaques is linear when seen in profile (Fig. 8.40), but when it is seen en face the appearance is variable (Fig. 8.41), the most common type being ‘holly leaf’ calcification (Fig. 8.42). Extensive pleural calcification may be lacelike. Pleural plaques may occur on the visceral pleura, including the interlobar fissures (Fig. 8.43).^{265. and 266.} Smooth visceral pleural thickening due to plaque must be distinguished from the more irregular subpleural fibrosis which occurs in patients with asbestosis. ²⁶⁷ Asbestos exposure may be associated with pericardial fibrosis, with or without calcification or effusion.^{268. and 269.} Yazicioglu, ²⁷⁰ in a study of 511 cases of pleural disease secondary to environmental exposure to chrysolite asbestos in Turkey, found 1.7% of cases with coincident pericardial calcification. Asbestos-related pericardial fibrosis may lead to constrictive pericarditis.^{268. and 271.}

The differential diagnosis of pleural plaques includes extrapleural fat deposition in obesity, ²⁷² extrapleural thickening in relation to multiple rib fractures, postinflammatory pleural thickening, and pleural metastases. In practice, the most frequent simulator of asbestos-related pleural plaque formation is extrapleural fat deposition. ²⁷³ Extrapleural fat may be differentiated from pleural plaques by its lower density, its smooth, undulating outline, and by the fact that it typically extends all the way to the lung apices (Fig. 8.44). However, this distinction is sometimes inaccurate. Fat is most abundant over the fourth to eighth ribs and does not involve the costophrenic sulci. CT will readily distinguish between soft tissue density of pleural plaques and extrapleural fat.

Although the presence of pleural plaques is associated with less physiologic impairment than diffuse pleural thickening, several studies have indicated that identification of plaques on chest radiographs is associated with evidence of pulmonary restriction, independent of the presence or extent of radiographic parenchymal abnormality.^{274.275.276.277. and 278.} Some of this association might be explained by the presence of subradiographic asbestosis.^{279. and 280.}

CT is substantially more sensitive than the chest radiograph for detection of pleural plaques (Fig. 8.45).^{281.282.283. and 284.} Contiguous CT imaging maximizes sensitivity for plaques. ²⁸⁵ CT is also more sensitive than radiographs for detecting calcification in plaques. ²⁸⁶ Elevated plaques may indent the adjacent lung, and may even cause ground-glass abnormality by interfering with subjacent pulmonary expansion. Thinner plaques may be difficult to distinguish from the intercostal musculature, but may be identified by recognizing that they overlay ribs as well as intercostal spaces (Fig. 8.46). Meirelles et al. ²⁸⁷ developed a detailed semiquantitative scoring system for determining extent of pleural plaques, which might be of value in assessing correlation with physiology. Weber et al. ²⁸⁸ found that high-resolution and radial MRI was almost as sensitive as CT for detection of pleural plaque. However, since CT is more sensitive for parenchymal abnormalities, it seems likely that it will remain the primary technique for detection of asbestos-related pleural disease.

It is important to distinguish between asbestos-related diffuse pleural thickening and pleural plaques because patients with diffuse pleural thickening commonly have marked impairment of pulmonary function. The radiographic definition of diffuse pleural thickening has varied. The ILO classification defines it as pleural thickening that involves the costophrenic sulci (Fig 8.47), ¹⁴³ while McLoud et al. ²⁴⁸ also included patients in whom pleural plaques occupied more than a quarter of the chest wall. Most studies have used the more restrictive ILO definition. On CT scanning, the definition of diffuse pleural thickening has also varied. Lynch et al. ²⁶⁷ defined it as an area of pleural thickening more than 3 mm thick, more than 5 cm in transverse dimension, and more than 8 cm in craniocaudal dimension. However, Copley et al. ²⁸⁹ defined diffuse pleural thickening as pleural thickening with tapered margins, in contrast to pleural plaques, which were required by this definition to have well-defined margins. Since diffuse pleural thickening, by all definitions, is associated with physiologic impairment,^{277.289. and 290.} the precise definition of this entity is of little importance.

Asbestos-related diffuse pleural thickening must be distinguished from the visceral pleural and subpleural fibrosis which occurs in patients with many forms of lung fibrosis (including asbestosis). Pure parietal pleural thickening is usually sharply defined on CT, while visceral subpleural fibrosis is associated with fine fibrous strands extending into the underlying lung, giving an irregular demarcation to the pleural process (Fig. 8.48).^{267. and 291.} Visceral subpleural fibrosis is usually, but not always, associated with other evidence of lung fibrosis. Differential diagnosis of asbestos-related diffuse pleural thickening includes pleural thickening (usually unilateral) related to prior empyema, infection, or other cause. Interestingly, patients with asbestos-related diffuse pleural thickening have been found to have a more frequent history of coronary bypass surgery than other asbestos-exposed individuals, suggesting that thoracic surgery may have a synergistic role in development of this complication. ²⁹⁰ Diffuse pleural thickening can usually be differentiated from mesothelioma by the absence of pleural effusion or pleural masses.

Rounded atelectasis, also called folded lung, ²⁹² is a masslike area of lung collapse adjacent to an area of pleural thickening. The condition is not unique to asbestos-related pleural thickening, and may also be seen with any other cause of exudative or organizing pleural disease. ²⁹³ Though typically associated with benign pleural disease, it may sometimes be seen with mesothelioma. ²⁹⁴ Hanke and Kretzschmar²⁹⁵ proposed that rounded atelectasis occurs when an atelectatic area of lung becomes infolded during resorption of a pleural effusion. Other authors,^{296. and 297.} noting that rounded atelectasis is not always preceded by a pleural effusion, have suggested that it may result from centripetal contraction of a focus of visceral pleural fibrosis, causing buckling of the pleura and collapse of the underlying lung parenchyma.

The radiographic findings are characteristic (Box 8.11) (Fig. 8.49

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