Imaging of occupational lung diseases

INTRODUCTION — A multitude of diseases can result from occupational exposure to dust, fumes, smoke, and biological agents. The most common acquired occupational lung diseases include occupational asthma, bronchitis, bronchiolitis, hypersensitivity pneumonitis, acute toxic inhalant syndromes, pneumoconioses, and tumors.

Among these, occupational asthma is likely the most common, yet it displays only limited imaging manifestations. The other diseases, including the pneumoconioses, yield characteristic imaging features that are the focus of this review. The clinical manifestations, diagnosis, and management of asbestosis, berylliosis, flock worker's lung, and silicosis, as well as a general approach to the evaluation of interstitial lung disease, are discussed separately.

●(See "Asbestos-related pleuropulmonary disease".)

●(See "Chronic beryllium disease (berylliosis)".)

●(See "Flock worker's lung".)

●(See "Silicosis".)

●(See "Approach to the adult with interstitial lung disease: Clinical evaluation".)

●(See "Approach to the adult with interstitial lung disease: Diagnostic testing".)

BACKGROUND — Occupational lung diseases include the pneumoconioses (interstitial lung diseases), hypersensitivity pneumonitis, bronchiolitis, byssinosis, and occupational asthma. Pneumoconioses result from inhalation and deposition of inorganic particles and mineral dust with subsequent tissue reaction. Pneumoconioses can be subdivided into fibrogenic (eg, silica, coal, talc, asbestos), benign or inert (eg, iron, tin, barium), granulomatous (eg, beryllium), and giant cell pneumonia associated with hard metal inhalation (eg, cobalt) [1,2]. Occupational exposure to certain organic dusts, molds, and chemicals can lead to hypersensitivity pneumonitis, an inflammatory reaction that is reversible if exposure is stopped in the acute or subacute phases. In unusual circumstances, organic particles like nylon flock can induce interstitial lung disease when inhaled by workers [3]. (See "Flock worker's lung".)

Inhalation of noxious gases and fumes can lead to noncardiogenic (increased permeability) pulmonary edema, constrictive bronchiolitis, or irritant-induced asthma, while byssinosis refers to an acute bronchoconstrictor response to inhalation of raw cotton, hemp, or flax, especially with exposure to bales of cotton, spinning, or carding [4,5]. Except for noncardiogenic pulmonary edema, pulmonary function tests show airflow limitation, but the chest radiograph is normal. (See 'Noxious fumes and gases' below and 'Byssinosis' below.)

Four criteria have to be fulfilled in order to secure a diagnosis of occupational lung disease:

●Documented exposure to a noxious agent known to induce disease

●A clearly defined latent period between exposure to the suspected agent and the development of disease symptoms

●Clinical manifestations compatible with the recognized features of the diseases

●Exclusion of other disease entities that could conceivably be responsible for the clinical picture [6]

IMAGING CHARACTERISTICS OF PNEUMOCONIOSES — Chest radiography remains the initial imaging modality and represents the cornerstone for evaluation of workers according to the International Labor Office (ILO) classification. Despite the importance of chest radiography as a screening test for detection of parenchymal and pleural abnormalities, high-resolution computed tomography (HRCT), also called thin-section computed tomography, has higher sensitivity and specificity and is better able to characterize the pattern of parenchymal involvement [7-10]. Thus, in symptomatic workers, HRCT is used to identify disease not detected by chest radiograph and to clarify the pattern of disease when the chest radiographic diagnosis is uncertain [9]. Pleural abnormalities are also more reliably detected and characterized with CT scanning.

FDG-PET scanning can be useful in differentiating fibrotic conglomerate masses from active inflammatory masses and neoplastic lesions, although it may not be able to differentiate between active inflammation and neoplasia.

Types of imaging findings in occupational lung diseases — A variety of imaging findings have been associated with occupational exposures. Some are pathognomonic, such as for the pleural plaques with or without calcifications seen following asbestos exposure, while others are strongly suggestive, such as the multiple, sharply marginated, small, rounded opacities in the upper lung regions in silicosis.

●Diffuse lung disease is a feature of mineral dust-induced pneumoconiosis, organic dust-induced hypersensitivity pneumonitis, and pulmonary edema induced by toxic fumes (NO₂, SO₂, CL, NH₃) [11,12].

●Hyperexpansion of lungs can result from diffuse constrictive bronchiolitis (bronchiolitis obliterans), such as after exposure to toxic fumes. Similar hyperexpansion can occur in severe, chronic asthma or advanced emphysema.

●Focal nodules and masses can arise following some longstanding occupational exposures. Examples include conglomerate masses, also called progressive massive fibrosis in complicated silicosis or coal worker's pneumoconiosis; post-primary tuberculosis as a sequela of exposure to silica, and tumors (eg, after exposure to silica dust or asbestos in a cigarette smoker) [13].

●Pleural disease can be induced by asbestos fibers (eg, pleural plaques, benign asbestos-related pleural effusion, diffuse pleural thickening, malignant mesothelioma) and be a sign post for the cause of associated parenchymal lung disease.

The International Labor Office classification — In 1919, the League of Nations founded the International Labor Office (ILO) in order to study the epidemiology, classification, and prevention of occupational lung diseases. As part of this process, a working classification of chest radiographs in persons with pneumoconiosis was introduced in 1930 and has been revised a number of times since [14,15]. The ILO classification uses graphic descriptors, includes image quality assessment, and provides standard images. A high degree of reader variability can be observed depending on reader training and experience with the ILO classification system [16]. This classification is predominantly used for research and for screening and surveillance of workers in dusty occupations and as part of an examination for disability claims. It is not used in routine clinical care. It is presented here to provide an overview and to help classify the patterns that are typical for the different pneumoconioses.

In the ILO classification, multiple criteria are analyzed and characterized: exam quality, size, shape, distribution, and profusion of small opacities (rounded or irregular), presence and size of large opacities, presence and type of pleural abnormalities, as well as other important abnormalities. All of these features are characterized and coded according to a lexicon (form 1 and figure 1 and figure 2 and figure 3).

Small opacities are categorized according to shape and size. Small rounded opacities are named p (≤1.5 mm), q (1.6 to 3 mm), or r (>3 to 10 mm) (image 1 and image 2 and image 3). Small, irregular opacities are classified by width, as s (≤1.5 mm), t (1.6 to 3 mm), or u (>3 to 10 mm) (image 4 and image 5). The lungs are roughly subdivided into three zones: upper, middle, and lower zone or region.

Large opacities are defined as lesions greater than 1 cm in diameter. One or more large opacities whose longest dimensions do not exceed about 50 mm form category A (image 6). One or more large opacities whose combined longest dimensions exceed 50 mm, but do not exceed the equivalent area of the right upper lung zone form category B (image 7). One or more large opacities whose combined longest dimensions exceed the equivalent area of the right upper lung zone form category C (image 8).

FEATURES OF INDIVIDUAL PNEUMOCONIOSES — The individual pneumoconioses have typical presentations that are helpful in the diagnostic evaluation of workers who may have been exposed. A summary of these findings is provided in the table (table 1).

Silicosis — Silicosis results from inhalation of crystalline silica (SiO₂) in quartz, granite, or sandstone with subsequent fibrotic lung reaction and represents the most widespread pneumoconiosis in the United States. Occupations at risk for silicosis include mining, quarrying, drilling, and sandblasting. Rapidly progressing simple and complicated silicosis has been described in Spain in the manufacture of new construction materials like quartz conglomerate, artificial stone manufacture for kitchen and bathroom countertops [17,18]. (See "Silicosis".)

Silica particles need to have a diameter of less than 5 micrometers in order to reach alveoli. These toxic particles are phagocytized by macrophages that decay. Subsequent extrusion of lysosomal enzymes perpetuates the damage wrought by free silica particles. Consequently, radiographically visible lung disease continues to progress even after cessation of active exposure to silica [19,20].

Silicosis progresses through stages:

●Simple silicosis is characterized by innumerable, sharply marginated, small rounded opacities composed of hyalinized, collagenous nodules, with a predilection for dorsal aspects of the upper lobes (image 9 and image 10). High-resolution computed tomography (HRCT) of the lung commonly shows bilateral, symmetric, centrilobular, and perilymphatic nodules with sharp margination. These nodules can calcify in 10 to 20 percent of patients. Workers exposed to quartz conglomerates developed simple silicosis with multiple small nodules seen on HRCT scanning in 93.4 percent of affected individuals [18].

●Complicated silicosis refers to the confluence of small collagenous silicotic nodules that results in formation of large opacities, exceeding 1 cm in diameter. This confluence evolves into progressive massive fibrosis or conglomerate masses (image 11 and image 12 and image 13) that represent the hallmark of complicated silicosis. Conglomerate masses have a bias for the upper lobes and tend to migrate towards the hilar regions with sharp peripheral and poorly marginated medial margins, creating so-called "angel wings" appearance.

On CT scans, pericicatricial emphysema is a common occurrence in the periphery of these masses. Conglomerate masses are frequently hypermetabolic on positron emission tomography [21]. During the evolution of large opacities, the small rounded nodules become less conspicuous. This conversion from simple to complicated silicosis may take more than 10 years. In the cohort of artificial stone manufacture workers, 6.6 percent developed progressive massive fibrosis with an exposure duration of 12 ± 4.3 years [18].Slowly progressive fibrosing interstitial pneumonia with a pattern typical of usual interstitial pneumonia (UIP) may occur in about 10 percent of patients with longstanding silicosis, so called dust-related pulmonary fibrosis [21,22]. Patients with established silicosis exhibit an increased risk of lung cancer (image 14) [13]. (See "Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis", section on 'Chest imaging'.)

●Hilar and mediastinal lymph node enlargement due to reactive lymph node hyperplasia is relatively common in patients with silicosis and typically affects nodes at stations 4R, 4L, 7, and 8 (figure 4) [23]. Punctate calcification in the lymph nodes is common [23]. In addition, calcium salt deposits in the marginal lymph node sinus lead to characteristic eggshell calcification of lymph nodes (image 15). This development can be seen in up to 5 percent of workers with silicosis. Eggshell calcifications can also be found in coal worker's pneumoconiosis, long-standing sarcoidosis, or treated lymphoma.

●Tuberculosis occurs preferentially in patients with silicosis, displaying characteristic imaging features of post-primary tuberculosis (image 16). This common association of tuberculosis with silicosis is found in up to 25 percent of affected workers and may be related to the toxic effect of crystalline silica on alveolar macrophages with subsequent weakening of innate immune responses and increased susceptibility to mycobacteria. Tuberculous upper lobe masses, consolidations, or cavities need to be differentiated from conglomerate masses of complicated silicosis or bronchogenic carcinoma [12].

●Acute silicosis is a rare manifestation of massive, rapid exposure to silica dust [24,25]. In particular, sandblasters, including denim sandblasters [26,27], can be exposed over a period of only several months to excessive concentrations of silica crystals that overwhelm alveolar macrophages. Subsequently, type II pneumocytes phagocytose dust and produce large amounts of surfactant. The result is silicoproteinosis with alveolar filling, similar to pulmonary alveolar proteinosis, also known as pulmonary alveolar lipoproteinosis (image 17). Radiographic findings include diffuse ground-glass opacities, consolidation, and a "crazy paving" pattern with interlobular septal thickening and intralobular lines on a background of ground-glass opacity on HRCT [28,29].

●Pleural abnormalities in silicosis have been underemphasized and include unexplained pleural effusions in 11 percent and pleural thickening in up to 58 percent of affected workers [26]. Rounded atelectasis may be seen as well [21]. Parenchymal pseudoplaques have been described and occur due to coalescence of subpleural lung parenchymal nodules [12].

An increased incidence of autoimmune diseases is seen in workers with silicosis. Erasmus syndrome refers to the possible association of occupational exposure to silica with the development of scleroderma [19,30-35]. The role of silica exposure as a potential risk factor for scleroderma is discussed separately. (See "Risk factors for and possible causes of systemic sclerosis (scleroderma)", section on 'Noninfectious environmental factors'.)

Coal worker's pneumoconiosis — Coal worker's pneumoconiosis (CWP) results from inhalation and deposition of coal dust particles. Depending on the location and type of mining activity, coal mine dust can contain high concentrations of respirable silica and silicates, which account for at least some of the cases of rapidly progressive lung disease [36,37]. In such cases diffuse dust-related fibrosis due to chronic pneumonia in mixed-dust pneumoconiosis with an atypical idiopathic pulmonary fibrosis pattern has been described with honeycombing and ground-glass opacification [22]. (See 'Silicosis' above.)

Inhalation of coal dust particles induces the formation of peribronchovascular coal macules. CWP has similar radiographic features to silicosis, but is classified as a separate disease due to its rather characteristic pathologic findings. In simple CWP, pigment and reticulin fibers accumulate in a peribronchiolar location. Over time, large amorphous black masses develop that occasionally have a liquified center. Subsequent cavitation can be the result of ischemic necrosis or post-primary tuberculosis.

Radiologically, these pathological findings produce small, rounded, nodular opacities, less than 1 cm in diameter, with a preference for the upper lobes (image 18 and image 19). This form is called simple coal worker's pneumoconiosis. Eventually, confluence and development of large opacities lead to the formation of complicated coal worker's pneumoconiosis with progressive massive fibrosis (image 20 and image 21 and image 22) [38]. The same predilection for the upper lobes is observed in coal worker's pneumoconiosis as in silicosis [20,39].

A substantial minority (10 to 40 percent) of coal miners with coal worker's pneumoconiosis develop diffuse pulmonary fibrosis, displaying small irregular opacities in the lower lung regions on chest radiographs [21]. These reticular opacities correlate better with the degree of pathophysiologic impairment of lung function than the concurrent small rounded opacities. On thin-section CT scanning these reticular opacities can be accompanied by honeycombing and have a similarity to UIP. This pattern of pulmonary fibrosis can be associated with bronchogenic carcinoma in the region of fibrosis [21].

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is commonly used to evaluate lung nodules. In six patients with CWP and a total of 19 nodules >1 cm, FDG-PET showed positive uptake in 18 of the nodules, although pathologic examination and follow-up did not find any evidence of malignant tumor [40]. Due to the high rate of false positive results, FDG-PET imaging is of limited utility in diagnosing malignant tumors in CWP [41].

Caplan syndrome is a rare complication of coal worker's pneumoconiosis that occurs concurrently with joint manifestations of rheumatoid arthritis. In this disorder peripheral lung nodules with the histopathology of rheumatoid nodules develop on a background of pneumoconiotic opacities. The syndrome was first described in Welsh coal miners but can be observed in other pneumoconioses as well. Radiologically, these workers develop typically bilateral, peripheral nodules 5 mm to 5 cm in size. In contrast to pneumoconiotic masses, they can develop rapidly, over a period of weeks, and may cavitate or calcify.

Talcosis and talc granulomatosis — Talc powder is composed of crystalline hydrous magnesium silicate. Occupational exposure to talc (eg, ceramic, paper, plastics, rubber, paint, and cosmetic industries) can lead to formation of rounded small opacities in the lung similar to silicosis (image 23) [42,43]. CT imaging shows small centrilobular and subpleural nodules, conglomerate masses with focal areas of high attenuation, and focal ground-glass opacities [43,44]. Relative sparing of the lung bases is typical. (See 'Silicosis' above.)

Talc can be contaminated with amphibole asbestos fibers. These impurities produce added small irregular opacities and pleural plaques [45]. (See 'Asbestos-related thoracic diseases' below and "Asbestos-related pleuropulmonary disease", section on 'Pleural plaques and diffuse pleural thickening'.)

Talc granulomatosis, also known as excipient lung disease [46], results from intravenous injection of crushed tablets and is obviously not a pneumoconiosis. These latter patients frequently develop micronodules (image 24), pulmonary fibrosis, upper lobe conglomerate masses, pulmonary arterial hypertension, and lower lobe emphysema. Foreign body granulomatosis is discussed separately. (See "Foreign body granulomatosis".)

Vineyard sprayer's lung disease — Vineyard sprayer's lung disease is a very rare occupational lung disease that has been described in Portuguese vineyard workers after inhalation of Bordeaux mixture. Bordeaux mixture is composed of copper sulfate with limewater (calcium hydroxide in solution) and has fungicidal qualities [47]. The disease represents a toxic response to the sprayed chemicals inhaled by the workers. Radiographs demonstrate nodular opacities, lobar consolidation, upper lobe scarring, conglomerate shadows, and lung destruction (image 25).

Hard metal pneumoconiosis — Hard metal pneumoconiosis is elicited by exposure to dust from hard metal objects, such as those produced during processing of cobalt. "Hard metal" is different from heavy metal and is produced by compacting powdered tungsten carbide with cobalt in a process called sintering [48-50]. Cobalt appears to be the dangerous constituent based on hard metal pneumoconiosis occurring in diamond polishers who are exposed to cobalt but not the other constituents of hard metal [51]. Asthma and diffuse interstitial fibrosis are the two most common manifestations of hard metal pneumoconiosis. Obliterative bronchiolitis is reported to be an early manifestation of cobalt exposure.

Histopathologic analysis reveals an accumulation of alveolar macrophages and multinucleated giant cells in the alveolar spaces, known as giant cell pneumonia. Analysis of the lung biopsy specimen for constituents of hard metals typically identifies tungsten and/or titanium; cobalt is not normally seen as it is soluble [49,50].

Radiographically, small nodular and reticular opacities and small cystic spaces can be found with basal predominance that can progress to diffuse involvement. On CT scanning, diffuse ground-glass opacities, centrilobular ground-glass nodules, consolidation, reticular opacities, and traction bronchiectasis are common [1,2,52].

Asbestos-related thoracic diseases — Asbestos is a naturally occurring fibrous magnesium silicate that can be woven into thermal insulating material. Primary occupational exposure occurs in asbestos mining and milling. Secondary occupational exposure occurs with insulation work, brakes, shipbuilding, construction, and textiles. Nonoccupational, indirect, or bystander exposure occurs through air pollution or among household members of asbestos-exposed workers.

Several types of asbestos mineral are mined: chrysotile (known as white asbestos) presents with serpentine fibers; amphibole (crocidolite or blue asbestos, amosite or brown asbestos, anthophyllite, and tremolite) forms long, rod-like fibers, which are believed to be more toxic. Other mined minerals like vermiculite can contain relevant amounts of tremolite asbestos fibers that can induce disease, as shown in residents of Libby, Montana [21,53].

Pleural disease — A spectrum of pleural diseases is associated with asbestos exposure, including pleural plaques, diffuse pleural thickening, benign asbestos pleural effusions, and malignant mesothelioma. These processes are discussed in greater detail separately. (See "Imaging of pleural plaques, thickening, and tumors" and "Asbestos-related pleuropulmonary disease", section on 'Pleural disease'.)

●Pleural plaques – Pleural plaques are the most common manifestation and a signpost of asbestos exposure, which is helpful when evaluating a patient with diffuse interstitial lung disease [54]. A latent period of 20 to 30 years separates exposure to asbestos and formation of radiographically visible pleural plaques. Plaques display slow growth and occur mostly on the parietal and diaphragmatic pleura. They have a predilection for the posterior and lateral surfaces of the thoracic cavity and form particularly over the ribs; they spare the apices and costophrenic sulci. A CT study of 1011 asbestos-exposed workers demonstrated pleural plaques in 47 percent [21,55].

While most persons with asbestos-related pleural plaques are asymptomatic, in some populations their radiographic presence is associated with restrictive lung function [21,53].

Radiologically, asbestos-induced pleural plaques form one-edged, curvilinear lesions in profile and geographic, scalloped, or holly-leaf like opacities en face; up to 80 percent are calcified and radiologically manifest as a sunburst, punctate, or candle-dripping pattern. They may have rolled margins or incomplete borders on chest radiographs. On CT-scans, pleural plaques display a table mountain or nodular configuration (image 26 and image 27 and image 28 and image 29). Pleural plaques induce proliferation of excessive adipose tissue in the extrapleural space, which also contains the endothoracic fascia and innermost intercostal muscle [56].

Diaphragmatic pleural plaques are pathognomonic for asbestos-related pleural disease and cause either an irregular, serrated contour or table mountain-like structures (image 30 and image 31 and image 32 and image 33).

●Benign asbestos pleural effusion – Benign asbestos pleural effusions occur relatively early after a latent period of 10 to 12 years or less post exposure. These exudative pleural effusions are unilateral in 90 percent of cases, recur in 30 percent of affected persons, and can persist up to a year (image 34 and image 35) [57,58]. These pleural effusions can clear spontaneously, or can form massive visceral pleural fibrosis with diffuse pleural thickening in up to 20 percent of afflicted individuals.

●Rounded atelectasis – Rounded atelectasis, which should be considered in the differential diagnosis of peripheral lung nodules or masses, is a form of peripheral atelectasis frequently associated with pleural thickening or pleural effusion [59,60]. A cleft-like invagination of visceral pleura isolates and collapses a subsegment of lung to form a subpleural mass. Bronchi and vessels that connect the mass to hilar structures form a so-called comet tail or vacuum cleaning effect. Rounded atelectasis occurs preferentially in the dorsal aspects of the lower lobes (image 36 and figure 5). The radiographic features of a subpleural mass with loss of volume, comet tail, and accompanying pleural thickening or effusion are characteristic and frequently allow differentiation from bronchogenic carcinoma.

●Diffuse pleural thickening – Diffuse pleural thickening starts unilaterally in the basal pleura after a latency of 20 years or longer [21] and progresses to a bilateral process. It represents primarily visceral pleural disease (image 37) [61]. The costophrenic sulci are regularly involved. The apical pleura can be involved as well. In the ILO classification, blunting of a costophrenic sulcus is a necessary condition for the diagnosis of diffuse pleural thickening. Asbestos-induced diffuse pleural thickening is 40 times less common than pleural plaques.

Diffuse visceral pleural thickening can lead to accompanying pleurogenic fibrosis or retractile pleuritis with fibrous bands extending into the adjacent lung parenchyma (image 38). The overall process results in restrictive pulmonary pathophysiology.

●Malignant mesothelioma – Malignant mesothelioma is strongly linked to asbestos exposure [62]. A latent period of 30 to 45 years is common. The clinical presentation, radiographic features, diagnosis, and staging of malignant mesothelioma are discussed separately. (See "Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma".)

Findings on chest radiographs and CT scans include pleural effusions, nodular pleural masses, thick, lobular or smooth diffuse pleural thickening exceeding 1 cm in thickness, thickening of interlobar fissures, circumferential pleural involvement, including the mediastinal pleura, or a combination of these multiple manifestations (image 39). Tumor spread may be noted to the contralateral pleural space, pericardium, chest wall, or peritoneum. Primary pericardial malignant mesothelioma can on rare occasions occur as well.

Asbestosis — Asbestosis represents pulmonary fibrosis induced by inhalation of asbestos fibers. The detection of asbestos fibers and ferruginous bodies within the lung parenchyma allows for differentiation from other forms of pulmonary fibrosis. The epidemiology, clinical manifestations, and diagnosis of asbestosis are discussed separately. (See "Asbestos-related pleuropulmonary disease".)

As with the pathologic predilection for the lower lobes, chest radiographs in asbestosis show fine, peripheral, reticular opacities as well as coarse linear and reticular opacities with a lower lung zone predominance (image 40 and image 4 and image 5).

On HRCT, subpleural fibrosis with parenchymal bands, subpleural curvilinear lines (image 41), interlobular septal thickening, intralobular lines, irregular opacities, traction bronchiectasis, and honeycombing are characteristic imaging findings. The posterobasal regions of the lungs are frequently involved first. In approximately a third of patients with documented, relevant occupational exposure to asbestos fibers and with a normal chest radiograph, HRCT may show subtle findings suggestive of asbestosis (image 42 and image 43) [58]. In a CT study of 1011 asbestos-exposed workers, the prevalence of features of asbestosis on imaging was 6 percent [21,55].

Constrictive pericarditis due to asbestos exposure represents a rare complication of asbestos exposure, leading initially to pericardial and pleural effusions and eventually to pericardial thickening and calcifications with involvement of the atrioventricular groove and subsequent distention of both atria due to inflow obstruction into the cardiac ventricles [63].

Bronchogenic carcinoma — Inhalation of asbestos fibers increases the risk for bronchogenic carcinoma, in addition to increasing the risk of malignant mesothelioma. The lung tumors occur mostly in the lower lobes, and adenocarcinoma is the usual histology (image 44 and image 45). (See "Asbestos-related pleuropulmonary disease", section on 'Malignancy'.)

Benign or inert dust pneumoconiosis — Benign or inert dust pneumoconioses occur in occupations in which workers inhale inert dusts such as iron oxide, tin oxide, or barium sulfate. Exposure to these inert dusts produces no obvious ill-effect on the structure and function of the lung; only minimal stromal reaction is noted on pathology [12].

Siderosis occurs in electric-arc and oxyacetylene welders who inhale small particles of iron oxide during the course of their work. In contrast to the lack of clinical signs and symptoms, the radiographic findings can be impressive with high attenuation micronodules and reticular opacities (image 46). The micronodules do not reflect fibrosis but rather radiopaque accumulation of metal particles within alveolar macrophages. On CT scanning, these nodules are frequently found in a centrilobular location; patchy ground-glass opacities may also be present [64]. Of note, some of these radiographic findings are reversible and may resolve almost completely after exposure ceases.

Other inert dust pneumoconioses are stannosis and baritosis, related to tin oxide or barium sulfate inhalation, respectively [12,65].

Beryllium disease/berylliosis — Chronic beryllium disease (CBD), also called berylliosis, is a granulomatous lung disease caused by exposure to beryllium, a lightweight metal previously used in fluorescent lights and currently used in the dental, computer, nuclear weapons, and nuclear reactor industries as well as aerospace industries. Community-acquired chronic beryllium disease has also been described in a neighborhood surrounding a beryllium-manufacturing plant [66]. CBD affects approximately 5 to 20 percent of exposed workers and differs from other classic pneumoconioses. It has features of hypersensitivity, ie, it represents a granulomatous hypersensitivity reaction to inhaled beryllium and its incidence and severity are not clearly related to the duration and intensity of exposure to the toxicant. Persons with a genetic predisposition may develop the disease after relatively minor exposure [21]. The latency period from initial beryllium exposure to onset of symptoms varies from three months to 30 years. Lung pathology in CBD reveals noncaseating granulomata, similar to sarcoidosis. Acute massive exposure to beryllium leads to a rare toxic reaction called acute berylliosis, characterized by noncardiogenic pulmonary edema or toxic pneumonia [67]. The epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of chronic beryllium disease are discussed separately. (See "Chronic beryllium disease (berylliosis)".)

On chest radiographs, multiple small rounded opacities that may be calcified are noted. Confluence of these opacities, architectural distortion due to scarring, and loss of volume with conglomerate shadows and an upper lobe predominance characterize the advanced stages of berylliosis (image 47 and image 48 and image 49). Hilar and mediastinal lymph node enlargement is common. Pericicatricial emphysema with bulla formation, spontaneous pneumothorax, and pulmonary arterial enlargement, as a result of pulmonary hypertension with cor pulmonale, are further late complications.

On CT scans, ground-glass opacities have been the earliest radiographic feature of berylliosis. In later stages, small nodules can be seen along bronchovascular bundles and in perilymphatic distribution in the interlobular septa and in subpleural location [67,68]. Thickened septal lines, ground-glass opacities, cystic cavitation, and bronchial wall thickening may be present. Enlarged lymph nodes in the hilum or mediastinum can be seen in about 25 percent of cases [69].

Overall, the clinical and radiographic picture can resemble that of sarcoidosis and in a series of patients with presumed sarcoidosis up to a third of cases turned up to have chronic berylliosis [70]. Beryllium's ability to produce a beryllium-specific immune response (beryllium lymphocyte proliferation test) is used to confirm a diagnosis of CBD and exclude sarcoidosis [67]. (See "Chronic beryllium disease (berylliosis)", section on 'Diagnosis'.)

Hypersensitivity pneumonitis — Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis (EAA) is an immunologically mediated interstitial lung disease that can be a form of pneumoconiosis caused by repeated inhalation and sensitization during occupational exposures to agents such as agricultural dusts, bioaerosols of microorganisms (fungal, bacterial, or protozoan), or reactive chemical species in a susceptible host [21,71,72]. It can initially mimic the clinical picture of an acute viral infection. It is a complex syndrome that is best understood as an allergic bronchiolitis induced by a plethora of allergens and haptens [73]. For example, farmer's lung and humidifier lung are due to thermophilic actinomycetes; bird fancier's lung results from avian protein in feathers and feces; cheese worker's lung is caused by Penicillium species; and epoxy resin lung is caused by phthalic anhydride. In a Mayo Clinic series of HP, avian antigens accounted for 34 percent of cases, hot tub lung (atypical mycobacteria) for 21 percent, and farmer's lung for 11 percent; no causative antigen could be identified in 25 percent [74].

The clinical presentation of HP has been historically categorized as acute and subacute, versus chronic depending upon the frequency, length, and intensity of exposure and upon the duration of subsequent illness. It must be emphasized, though, that the clinical presentation of hypersensitivity pneumonitis is variable: the patients don’t always fit neatly into the conventional categories of acute, subacute, and chronic HP. The distinction between acute and subacute HP can be particularly problematic. The causes, classification, diagnosis, and management of hypersensitivity pneumonitis are discussed separately. (See "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Epidemiology, causes, and pathogenesis" and "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Clinical manifestations and diagnosis" and "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Treatment, prognosis, and prevention".)

The histopathologic correlate consists of chronic bronchial and peribronchiolar inflammatory changes with giant cells in the interstitium and alveoli of the lung parenchyma. Eventually, pulmonary fibrosis may develop.

The imaging features of hypersensitivity pneumonitis are best displayed with HRCT scanning. It can be classified according to imaging manifestations into cluster 1 and cluster 2 hypersensitivity pneumonitis. Cluster 1 combines acute and subacute hypersensitivity pneumonitis and includes diffuse or multifocal centrilobular ground-glass nodules with superimposed mosaic attenuation with a lobular distribution (image 50 and image 51) [73,75-77]. The combination of ground-glass opacities, normal lung, and lobular gas-trapping with mosaic attenuation can lead to a geographic appearance, the so-called headcheese pattern named for its resemblance to a sausage made from the head of a hog, better named three-attenuation pattern, on CT images [78]. The lung bases tend to be spared.

Cluster 2 hypersensitivity pneumonitis, refers to chronic hypersensitivity pneumonitis and is associated with fibrotic strands radiating from the hilar regions, if the axial interstitium is preferentially involved, or reticular opacities and honeycombing in the periphery of the lung, similar to usual interstitial pneumonia (image 52 and image 53). Fibrotic changes tend to start in the lower lung zones and advance towards the upper lung regions, as the disease progresses. The endstage of chronic hypersensitivity pneumonitis can lead to severe upper lobe scarring, cicatrizing atelectasis, and lung parenchymal distortion similar to other chronic granulomatous processes. Emphysema and cysts may also occur in chronic cases of hypersensitivity pneumonitis [79]. The presence of findings of fibrosis on high-resolution CT scanning correlates with a poor prognosis [80,81].

NOXIOUS FUMES AND GASES — Inhalation of noxious gases and fumes, including nitric acid (solution of NO₂ in water), sulfur dioxide (SO₂), chlorine gas (Cl), and ammonia (NH₃) can lead to acute injury, such as noncardiogenic, increased permeability, pulmonary edema (eg, nitric acid, chlorine, phosgene) [82-86], irritant-induced asthma, or delayed onset of obliterative bronchiolitis (also known as bronchiolitis obliterans) [87-90]. The clinical manifestations and diagnosis of noncardiogenic, increased permeability, pulmonary edema and constrictive bronchiolitis are discussed separately. (See "Noncardiogenic pulmonary edema" and "Irritant-induced asthma" and "Overview of bronchiolar disorders in adults".)

In obliterative bronchiolitis and irritant-induced asthma, the chest radiograph may be normal or may show hyperexpansion. High-resolution computed tomography (HRCT) of the lung parenchyma in constrictive bronchiolitis may show a mosaic pattern of attenuation characterized by lobular or subsegmental areas of hypoxic vasoconstriction on inspiratory scans and gas-trapping on expiratory scans (radiolucent, low-attenuation) interspersed with normal lung which is hyper-perfused (ground-glass like, higher attenuation opacities) (image 54) [91].

BYSSINOSIS — Byssinosis results from long-term inhalation of dusts produced in the processing of raw cotton, flax, hemp, and possibly sisal [4,5,92]. The typical clinical features are chest tightness, cough, and dyspnea that peak one to two hours into the first day of the work week and gradually lessen over the course of the week. These symptoms are associated with airflow limitation on pulmonary function testing [93]. Chronic exposure can lead to a chronic productive cough and gradually worsening airflow limitation, resembling chronic bronchitis, but is not associated with radiographic abnormalities.

NEWER OCCUPATIONAL LUNG DISEASES

●Ardystil syndrome – Ardystil syndrome was described in Spain after inhalation of aerosolized Acramin FWN used in textile printing resulted in the development of organizing pneumonia. CT scanning demonstrated bilateral, peripheral-predominant, patchy foci of parenchymal consolidation [94]. (See "Cryptogenic organizing pneumonia".)

●Flock worker's lung – Flock worker's lung arises from respirable flock, an ultra-fine nylon fiber used in the production of certain fabrics; it results in nongranulomatous interstitial lung disease characterized by lymphoid hyperplasia, lymphocytic, follicular bronchiolitis and peribronchiolitis. On high-resolution CT (HRCT) scanning diffuse micronodularity, patchy ground-glass opacities, and patchy regions of consolidation are often seen [3,95]. (See "Flock worker's lung".)

●Flavor worker's lung – Flavor worker's lung was described in patients exposed to the artificial butter flavoring chemical, diacetyl (2,3-butanedione), leading to constrictive bronchiolitis (obliterative bronchiolitis). HRCT scanning shows a mosaic attenuation pattern [89,96]. (See "Overview of bronchiolar disorders in adults", section on 'Causes'.)

●Indium-tin oxide lung disease – Indium-tin oxide, utilized in the production of transparent conductive films utilized in flat-panel screens can lead to interstitial lung disease, including pulmonary fibrosis, and pulmonary alveolar proteinosis [97]. CT findings include subpleural honeycombing, upper lobe predominant fine nodular opacities, ground-glass opacities with "crazy-paving," and associated emphysema [21,97]. (See "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults".)

●Hydrochlorofluorocarbon pulmonary edema – Hydrochlorofluorocarbon (HCFC)-141b (1,1-dichloro-1-fluoroethane) exposure in electronic factories producing circuit boards can induce acute pulmonary toxicity with increased permeability pulmonary edema that can resolve spontaneously [21,98].

●Lung disease in deployed military personnel – Bronchiolitis obliterans has been reported in returning service members exposed to combustion products from industrial sulfur fires and other noxious gases and fumes in Iraq or Afghanistan. Thin-section CT scanning reveals centrilobular nodules and gas-trapping as well as mosaic pattern of attenuation [21,99].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pneumoconiosis".)

SUMMARY

●Definitions

•Occupational lung diseases occur as a direct result of workplace exposure to metals, dust, fumes, smoke, or biologic agents. These disorders include interstitial lung disease (pneumoconiosis and occupational hypersensitivity pneumonitis), bronchitis, bronchiolitis, asthma, and tumors. (See 'Introduction' above.)

•Pneumoconioses result from inhalation and deposition of inorganic particles and mineral dust with subsequent reaction of the lung. Pneumoconioses can be subdivided into fibrogenic (eg, silica, coal, talc, asbestos), benign or inert (eg, iron, tin, barium), granulomatous (eg, beryllium which induces a sarcoid-like reaction), and giant cell pneumonia in cobalt inhalation. (See 'Background' above.)

●Pneumoconiosis Diagnosis

•Pneumoconioses are usually diagnosed by a positive exposure history and suggestive radiographic presentation. An understanding of the pathology and radiographic appearance facilitates the evaluation, diagnosis, and management of these workers (table 1). (See 'Background' above and 'Imaging characteristics of pneumoconioses' above.)

•Given the typical radiographic appearance of the most common pneumoconioses, tissue biopsy is usually not required to establish the diagnosis when the exposure history and radiographic pattern are characteristic. (See 'Imaging characteristics of pneumoconioses' above.)

●Specific imaging patterns in pneumoconioses

•Diffuse lung disease is a feature of mineral dust-induced pneumoconiosis, organic dust-induced hypersensitivity pneumonitis, and pulmonary edema induced by toxic fumes. (See 'Types of imaging findings in occupational lung diseases' above.)

•Hyperexpansion of lungs can result from diffuse constrictive bronchiolitis (bronchiolitis obliterans), such as after exposure to toxic fumes. Similar hyperexpansion can occur in severe, chronic asthma or emphysema. (See 'Types of imaging findings in occupational lung diseases' above and 'Noxious fumes and gases' above.)

•Focal nodules and masses can arise following some longstanding occupational exposures. Examples include conglomerate masses in complicated silicosis or coal worker's pneumoconiosis; post-primary tuberculosis as a sequela of exposure to silica, and tumors (eg, after exposure to silica or asbestos in a cigarette smoker). (See 'Silicosis' above and 'Coal worker's pneumoconiosis' above and 'Bronchogenic carcinoma' above.)

•Pleural plaques are the most common manifestation of asbestos exposure. They are a sign post of prior asbestos exposure and are helpful when evaluating a patient with diffuse interstitial lung disease. (See 'Pleural disease' above.)

●International labor office (ILO) Classification

•The ILO classification de-emphasizes the characteristic radiologic presentation and emphasizes a standardized, graphic description and semiquantitative evaluation of radiographs in combination with an exposure history.

•This standardized classification system (form 1 and figure 1 and figure 2 and figure 3) is predominantly used for research, for screening and surveillance of workers in dusty occupations, and for the purpose of disability claims, but not for routine clinical care. (See 'The International Labor Office classification' above.)