Chapter E1: Pneumoconiosis

Pneumoconiosis is a general term for a collection of lung diseases caused by the inhalation and accumulation of usually inorganic dust particulates, generally from the workplace, and eliciting an injurious reaction of the lung tissue. Inhalational dust exposure can lead to benign and malignant diseases of the lung parenchyma, airway, and pleura. In this chapter, we outline the nonmalignant respiratory effects related to inhalational exposure to coal mine dust, asbestos, and silica; metals such as uranium and cobalt; as well as man-made vitreous fibers. As shown in Fig. E1-1, parenchymal pneumoconiosis may be classified as nodular lung diseases (including progressive massive fibrosis or PMF), dust-related diffuse pulmonary fibrosis (or secondary usual interstitial pneumonitis or UIP), other interstitial pneumonitis (including hypersensitivity pneumonitis from organic components of the dust), and alveolar proteinosis. Airway-dominant pneumoconiosis may be classified as the chronic bronchitis and/or emphysema phenotypes of chronic obstructive pulmonary disease (COPD), work-related asthma, and small airways diseases. Pleural changes of pneumoconiosis include pleural effusions, rounded atelectasis, circumscribed pleural thickening/pleural plaques, and diffuse pleural thickening. This chapter not only focuses on the nodular and fibrotic parenchymal lung diseases, but also considers the other protean manifestations of pneumoconiosis.

Epidemiology

Between 1980 and 2014, 57,033 deaths due to parenchymal pneumoconiosis were recorded in the death records from the U.S. National Center for Health Statistics.¹ Of these, 38% of the deaths were due to coal workers’ pneumoconiosis and 27% from asbestosis.¹ Regional variation in parenchymal pneumoconiosis mortality rates is seen in the United States; the counties with highest mortality rates are concentrated in central Appalachia, Mississippi, Colorado, Utah, and Montana, areas with a history of mining.¹ The mortality rate from parenchymal pneumoconiosis has declined by 49% overall between 1980 and 2014.¹ Since providers may not ask an occupational history,² and the occupational contribution to respiratory diseases such as “idiopathic” pulmonary fibrosis (IPF) may be missed, these data likely underestimate the true prevalence of and mortality from pneumoconiosis in the United States.

Pathogenesis

The inflammatory processes induced by dust inhalation and deposition lead to phagocytosis (i.e., indigestion of particles by phagocytes), lipidosis, and especially fibrosis of the target tissue.³ Although the particle size of the dust, its biologic potency, and cumulative exposure time and dose contribute toward determining the pathogenicity of the inhaled dust particles, individual susceptibility factors are also important.³ The inflammatory processes may progress long after cessation of exposure to the causative mineral, which may be retained in lung tissues.

Diagnosis

The diagnosis of pneumoconiosis requires consideration of the following clinical data^4–6:

• 1) Characteristics of exposure: Information on category (i.e., occupational, domestic, bystander, or environmental), intensity, and duration of exposure, and latency between exposure and disease, is usually obtained by an occupational history and/or questionnaire.²

• 2) Respiratory symptoms: Information includes specific symptoms (i.e., cough, exertional dyspnea, wheezing, and chest discomfort), duration (i.e., acute, subacute, or chronic), and course (nonprogressive vs. progressive).

• 3) Physical examination: Lung auscultation findings include prolongation of the expiratory phase, inspiratory crackles, inspiratory rhonchi, and expiratory wheezes.

• 4) Physiological changes: These include obstructive, restrictive, and mixed obstructive and restrictive ventilatory defects, as well as normal lung function with or without isolated desaturation with exercise. Assessment should include a spirometry test, followed by lung volume measurement if a restrictive defect is detected. Diffusing capacity for carbon monoxide (DLCO) and oximetry during activities may be more sensitive than spirometry in detecting early disease.⁷ Excessive decline in forced expiratory volume in one second (FEV₁) over time may precede the development of disease.⁸

• 5) Radiologic changes: These include chest radiographic and high-resolution computed tomography (HRCT) findings of respiratory diseases, as per the International Labor Organization (ILO) classification of chest radiographs for pneumoconiosis,⁹ and the international classification of HRCT.^10,11

• 6) Pathologic changes: Bronchoalveolar lavage, biopsy, and mineralogic analysis are rarely necessary to make the diagnosis, but may be useful to exclude alternative diagnoses.

• 7) Exclusion of alternative plausible causes for the clinical findings.

Management

Management of parenchymal pneumoconiosis includes appropriate vaccinations; outpatient pulmonary rehabilitation¹²; supplemental oxygen, as necessary at rest, exercise, or sleep; and the use of inhaled bronchodilators for the management of associated bronchospasm. For workers exposed to silica, latent and active tuberculosis should be detected and treated, particularly among human immunodeficiency virus (HIV)–infected workers.¹³ The use of antifibrotic agents has not been studied in the treatment of parenchymal pneumoconiosis. A recent study indicates that nintedanib, an intracellular inhibitor of tyrosine kinase, is effective in patients with progressive fibrosing interstitial lung diseases, including non-UIP fibrotic pattern, in decreasing the annual rate of decline in forced vital capacity (FVC).¹⁴ Selected pneumoconiosis such as hard metal lung disease (HMLD) may respond to systemic corticosteroid treatment.¹⁵ Lung transplantation, useful in advanced pneumoconiosis, is being increasingly used for coal miners with pneumoconiosis.¹⁶ Cor pulmonale, secondary polycythemia, and respiratory insufficiency and failure are all treated in the conventional manner.⁴

In addition to prescribing appropriate treatment, an important decision that a healthcare provider faces is whether the patient can return to work. Work restriction to prevent further exposure may help control progression of pneumoconiosis, but this often results in economic hardship or job loss. The patient may be eligible for medical benefits through the workers’ compensation system, and for benefits under the Black Lung Benefits Act for coal miners. Select uranium and nuclear weapons industry workers in the United States may qualify for benefits under the Radiation Exposure Compensation Act and the Energy Employees Occupational Illness Compensation Program Act. The role of the physician in this compensation process includes performing an objective evaluation of impairment once the patient has reached maximal medical improvement.

Prevention

Primary prevention of pneumoconiosis consists of maintaining respirable dust levels within legal limits, although this may not completely eliminate the risk of disease.⁵ Mitigation of respirable dust exposure can be accomplished through proper ventilation, use of water spray dust suppression, enclosure of dust-generating operations, and improved engineering control and work practices. Smoking cessation and maintenance of a healthy lifestyle is also encouraged.

Secondary prevention is aimed at diagnosing early stage disease and avoiding further lung injury. Exposed workers may be followed in a health surveillance program, with assessment of clinical history, spirometry, and chest X-rays periodically. Newer models of surveillance include use of mobile screening clinics with telemedicine in remote rural communities.¹⁷ Once a diagnosis of pneumoconiosis is established, patients require periodic monitoring every 3–5 years.⁴ Given the shortage of occupational medicine experts,¹⁸ and need for multidisciplinary management of pneumoconiosis, newer models of care may be considered. An example includes the use of structured telementoring of providers by creating a virtual “community of practice” approach. This approach has been proven to be effective in managing other chronic diseases.¹⁹

Introduction

Coal remains the second largest energy source worldwide. Internationally, coal consumption has steadily increased since 2000, driven largely by the increased demand in China and India.²⁰ The United States has the largest coal reserves globally, with the Powder River Basin of Wyoming and Montana being its largest coal producing region. The U.S. coal production decreased by about 2% year over year, amounting to about 750 million short tons in 2018.²¹ The U.S. coal production in 2018 was classified as follows (arranged in an increasing order of coal rank or hardness to reflect the degree of metamorphosis of the coal): lignite (8%), subbituminous (45%), bituminous (47%), and anthracite (0.3%).²¹ Anthracite deposits are associated with the highest rates of lung disease.²² Surface coal mining accounts for an increasing fraction of coal mined in the United States, particularly in the western states, while the underground mining workforce has been decreasing.²¹

In addition to carbon, coal contains silica, silicates (such as mica and kaolin), metals, and volatile compounds.²³ Airborne coal mine dust also contains silica and silicate particles generated as the neighboring rock in the coal seam is cut. Coal miners may be exposed to multiple other potential respiratory hazards in the mine, such as diesel engine exhaust; microbial bioaerosols²⁴; “rock dust” (a finely crushed powder composed of limestone and containing crystalline silica, which is applied to the mine surfaces to dilute the highly explosive finely dispersed coal dust)²³; and chemicals such as isocyanates (used in roof bolt glues, and as fire retardant for ventilation systems in polyurethane foam).²⁵ Prolonged inhalation of coal mine dust causes a spectrum of lung diseases collectively termed coal mine dust lung disease (CMDLD). “Black lung” is a generic term used legislatively and popularly to describe CMDLD.

Occupations at Risk

In 2019, almost 54,000 employees worked in U.S. coal mines.²¹ With 28% of the world’s recoverable coal reserves, mining employment in the United States is likely to remain significant for many years despite recent mine closures.²⁶ Significant exposure to coal mine dust may occur not only underground but also in surface mines (including strip and auger mines), in coal preparation plants, and in coal-handling operations. Workers engaged in face work and coal preparation often have the highest exposures to respirable coal dust and thus the highest rates of CMDLD. Some surface mine jobs such as drillers can involve high exposures to silica, especially if dust control measures are missing or ineffective.²⁷ Cumulative coal mine dust exposure is the most important factor in the development of CMDLD.²⁸

Prior to 1970, dust concentrations in face jobs in underground coal mines in the United States ranged from 6 to 10 mg/m³. Subsequent to the 1969 Federal Coal Mine Health and Safety Act,²⁹ dust levels were reduced to 2 mg/m³. Although these regulations reduced dust exposures in coal mines,³⁰ recent evidence suggests that the miners were not uniformly protected from developing disease.^31–34 In 2011, the U.S. National Institute for Occupational Safety and Health (NIOSH) recommended that exposure to respirable coal mine dust should be limited to 1 mg/m³.²⁷ In 2014, the U.S. Mine Safety and Health Administration (MSHA) reduced coal mine dust exposure to 1.5 mg/m³.³⁵

Epidemiology

Recent evidence points toward an ongoing increase in both the prevalence and severity of CMDLD since the late 1990s.^{26,31–34,36,37} The 2017 data from the NIOSH surveillance program showed a greater than 10% overall prevalence of radiographic pneumoconiosis for underground coal miners with over 25 years’ tenure. A 21% prevalence of radiographic pneumoconiosis was described in central Appalachian long-tenured miners.³⁶ The rate of PMF in long-tenured underground coal miners was 1.1% in 2014, compared to 0.3% at its nadir in the late-1990s.^37,38 The rate of PMF in central Appalachia reached 4.5% for the 5-year period ending 2017.³⁶ Most of the affected coal miners worked their entire careers after the 1969 dust limits had gone into effect, calling into question the effectiveness of modern dust controls in the United States. Nationwide, disease rates are elevated among miners working in smaller mines.³⁷

Pathogenesis

Based on experiments on rats, inhalation of coal mine dust causes an influx of inflammatory leukocytes and activated macrophages to the alveolar region.³⁹ The activated inflammatory cells demonstrate enhanced ability to degrade fibronectin, a key for maintaining lung structure. Following cessation of exposure, rats continue to show increased proteolysis of fibronectin by bronchoalveolar leukocytes.³⁹ Experimental lesions of emphysema were produced in rats after laryngotracheal injection of papain (a destructive biological enzyme) and coal dust.⁴⁰ The lesions observed were progressive.

Disease Phenotypes

CMDLD is a collection of respiratory diseases resulting from the parenchymal, airway, and pleural effects of the inhalational exposure to coal mine dust. As shown in Fig. E1-1, parenchymal CMDLD may be classified as nodular lung diseases (including classic coal workers’ pneumoconiosis or CWP, and PMF), dust-related diffuse pulmonary fibrosis (or secondary UIP),^41–43 other interstitial pneumonitis (including hypersensitivity pneumonitis from microbial aerosols),^23,44 and alveolar proteinosis.⁴³ Airway-dominant CMDLD may be classified as chronic bronchitis^45,46 and emphysema⁴⁷ phenotypes of COPD, work-related asthma,^25,48–50 and small airways diseases.⁵¹ Pleural changes in CMDLD include pleural effusions,^52,53 rounded atelectasis,⁵⁴ circumscribed pleural thickening/pleural plaques and diffuse pleural thickening.⁵⁵

Nodular Lung Diseases

Classic CWP is pathologically defined by the characteristic coal macule lesion, a 1–2 mm collection of coal dust and dust-laden macrophages in the periphery of the respiratory bronchioles. The coal macule may be surrounded by focal emphysema. Coal nodules are larger lesions containing a mixture of coal dust–laden macrophages, collagen, and reticulin. Coal nodules are responsible for the small opacities seen on the chest radiographs of miners with classic CWP. Radiologic changes described in the literature are small rounded opacities, not exceeding 1 cm in diameter, with bilateral upper lobe predominance. Recent evidence, however, indicates that the small opacities may either be equally distributed throughout all lung zones⁵⁶ or be lower lung zone predominant.⁵⁵ In addition, the small opacities may be irregular or linear on chest radiographs in 38–47% of coal miners.^55,56 With increased profusion of small opacities in the lung comes greater functional abnormalities, but some patients with CWP may not demonstrate significant respiratory symptoms or limiting physiologic impairment.

Complicated CWP or PMF is marked by the radiological presence of one or more opacities greater than 1 cm in size and occurring on a background of classic CWP. PMF lesions are typically upper lobe predominant and tend to be bilaterally distributed as disease progresses. Significant emphysema and fibrotic scarring with hilar distortion are often present. Higher profusion of classic CWP is associated with an increased risk of developing PMF, even after cessation of exposure.^57,58 Miners with PMF with large opacities of combined diameter greater than 5 cm have an increased mortality rate when compared to nonminers or miners with classic CWP.^59–61

The term “rapidly progressive’” CWP refers to the radiographic progression of more than one ILO profusion category (which defines the extent of radiologic change) of small pneumoconiotic opacities within 5 years, or the development of PMF after 1985 in the United States.³⁴ Data from 1996 to 2002 showed that 35% of newly diagnosed cases of CWP in the United States were “rapidly progressive.”³⁴ Miners with “rapidly progressive” disease were younger and more likely to work at the mine face and in small mines.³⁴ U.S. data suggest that respirable silica and silicate dust content from mining of thin coal seams may be a contributing factor to some “rapidly progressive” CWP.^43,62

Dust-Related Diffuse Fibrosis of the Lung

Coal mine dust exposure also contributes to the dust-related diffuse fibrosis phenotype of CMDLD, or secondary UIP.^41–43 The clinical, radiological, and functional characteristics of this disease mimics IPF,⁶³ but it generally has a more benign disease course with a longer survival time.⁶³ This phenotype of CMDLD may be misclassified as “idiopathic” in circumstances where an inadequate occupational history has been obtained,⁶⁴ with important implications for both disease management and prognosis.²⁶

Airway-Centric Diseases

Emphysema seen in CMDLD is most commonly the centriacinar type; pathologically, it is referred to as focal emphysema when a coal dust macule is also present. Bullous and panacinar emphysema have also been described and are part of the continuum of disease that may follow either smoking or coal mine dust exposure.^26,47,63,65 In an autopsy study, cumulative exposures to respirable coal mine dust or coal dust retained in the lungs were significant predictors of emphysema severity and the contributions of coal mine dust exposure and cigarette smoking toward emphysema severity were similar.⁴⁷

Chronic bronchitis, characterized pathologically by hypertrophy and hyperplasia of the bronchial mucous glands with an associated increase in the goblet cells of the small airways, occurs as a result of dust exposure. Clinically defined as the chronic production of phlegm, chronic bronchitis is a frequent clinical finding among coal miners, and its prevalence and incidence are related to dust exposure.^45,46

Prevention

The key to preventing CMDLD is prevention of prolonged inhalation of significant concentrations of coal mine dust. Secondary prevention strategies, for example, removal of miners with early evidence of CMDLD to low-dust jobs can assist in reducing the incidence of severe disease. This strategy was mandated by the U.S. Congress in the Federal Coal Mine Health and Safety Act of 1969²⁹ and has been implemented with substantial but incomplete success in underground operations of the U.S. coal industry.

Introduction

Silica or silicon dioxide, a naturally occurring mineral, is the main constituent of more than 95% of rocks and 59% of the mass of the earth’s crust.⁶⁶ Silica naturally occurs in crystalline and amorphous forms. Common forms of crystalline silica are quartz (the most commonly found form in nature), tridymite, and cristobalite.⁵ Silicosis is an incurable nodular and/or fibrotic parenchymal lung disease due to the inhalation of respirable crystalline silica.

Occupations at Risk

Silica-related lung disease is a major health issue for workers involved in earth works (such as mining) or products containing silica (such as masonry and cement work; Table E1-1).⁶⁷ Outbreaks of silicosis have been reported in several modern occupations, such as artificial (or engineered) stone benchtop fabricators,⁶⁸ denim jean sandblasters,^69,70 and jewelry/semiprecious stone polishers.⁶⁶ Environmental exposure to respirable silica in communities living in the vicinity of industrial sources of dust, such as quarries, has been reported to cause nonoccupational silicosis.⁵

Epidemiology

It is estimated that more than 2 million U.S. workers are currently exposed to respirable crystalline silica.⁷¹ The annual mortality from silicosis in the United States has declined since 2001 to 0.39 deaths per million in 2010.⁷² The risk of developing silicosis depends on the cumulative exposure of an individual during the working lifetime.⁵ However, about 10% of cases of silicosis in a recent surveillance study had less than 10 years of exposure to silica.⁷¹ A Turkish study of denim sandblasters with silicosis reported mean exposure durations of only 3.5 years.⁷⁰ The latter two studies indicate that some workers are sensitive to lower cumulative levels of silica exposure.⁷³ The susceptibility of an individual to disease is associated with their lack of clearing of inhaled dust in the lung, which may be affected by genetic factors, prior tuberculosis, or smoking.⁵ In addition, it is questionable whether currently acceptable levels of silica dust provide protection against development of lung disease.⁵

Pathogenesis

Inhalation and lung deposition of respirable silica particles leads to alveolar macrophage activation, which in turn upregulates several proinflammatory and profibrotic pathways. Subsequent ingestion of silica by alveolar macrophages leads to cell death, autophagy, and release of intracellular silica, which attracts further macrophages, creating a cascading effect, and leading to alveolitis and fibrosis.⁷⁴ One potential factor that contributes to pathogenicity is the characteristics of the particle. Recently fractured silica and fine particles can be more harmful and are more likely to lead to acute silicoproteinosis and accelerated form of silicosis.⁵

Disease Phenotypes

Nodular Lung Diseases

There are three described forms of silicosis, as noted in Table E1-2. Chronic silicosis is the most common form of the disease, and has two forms: chronic simple or nodular silicosis, and complicated silicosis or PMF. Chronic simple silicosis is characterized by discrete rounded lung nodules of up to 1 cm in size, usually in a bilateral upper lobe predominant distribution. These silicotic nodules may coalesce to form conglomerate masses of more than 1 cm in size, migrating toward the hilum, and causing distortion and destruction of the lung parenchyma, which is characteristic of PMF. Symptoms are usually seen once progression to PMF occurs, in the form of dyspnea and cough.⁵ In contrast to chronic silicosis, accelerated sclerosis is a more rapidly progressive disease, associated with shorter latency and higher intensity of exposure. Acute silicosis or silicoproteinosis, associated with very high intensity of exposure, may progress rapidly to respiratory failure and death.

Dust-Related Diffuse Fibrosis of the Lung

Animal models of experimental lung fibrosis utilize silica to induce a fibrogenic reaction of the lung.⁷⁵ In vitro studies similarly demonstrate lung scarring as a result of experimental silica exposure.⁷⁶ Dust-related diffuse fibrosis of the lung, radiologically and pathologically indistinguishable from IPF, is a recognized type of pneumoconiosis in workers exposed to silica,⁶³ with one study reporting this CT pattern in 12% of patients with silicosis and mixed dust pneumoconiosis.⁷⁷

Airway-Centric Diseases

COPD may occur in silica-exposed workers, with or without silicosis, independent of smoking.^78–82 Exposure to silica at dust levels that appear not to cause roentgenographically visible simple silicosis can cause chronic airflow limitation and/or mucus hypersecretion and/or pathologic emphysema.⁸³ In moderate to severe silicosis, silicotic nodules occur in close proximity to small and medium airways causing narrowing and distortion of the lumen, presenting with airflow obstruction. Hypertrophy and scarring in bronchial-associated lymphoid tissue and intrapulmonary lymph nodes may similarly compress larger airways.⁸⁴ Obstructive lung function pattern was noted in 17% of patients with silicosis who had never smoked in a U.S. silicosis registry.⁸⁵ The size of lung nodules and PMF were independent predictors of airflow obstruction in patients with silicosis in Hong Kong.⁸⁶ Among South African gold miners, the dust exposure intensity correlated with the extent of emphysema at autopsy, independent of silicosis.⁸⁷ A meta-analysis of 13 studies among coal and gold miners confirmed an excess of bronchitic symptoms and obstructive physiology, even among nonsmokers.⁸² There may be an additive effect between tobacco smoke and occupational silica exposure in producing chronic bronchitis and air flow obstruction.⁸³ Pathology studies of workers exposed to nonasbestos mineral dusts reveal pigmentation and fibrosis surrounding small airways.⁸⁸ This abnormality, to which the term mineral dust small airways disease has been applied, rarely occurs among subjects without dust exposure, and is associated with airflow obstruction in excess of that found among dust-exposed control subjects.⁸⁹

Radiologic Features

In addition to previously described silicotic nodules, other radiologic features include calcified nodules, cavitation, eggshell calcification of hilar lymph nodes (Fig. E1-2), pleural thickening,⁹⁰ and hilar and mediastinal lymphadenopathy.⁹¹ Cavitary lesions raise concerns for concomitant mycobacterium tuberculosis infection. The ILO classification of chest radiographs is used for screening silica-affected workers. HRCT scans of the chest are more sensitive than chest X-rays in the diagnosis of silicosis,⁵ and may be particularly useful in the detection of early PMF or in the evaluation of a patient with atypical radiologic signs with a differential diagnosis of other diseases.⁵ PET scan in patients with silicosis may demonstrate diffusely increased uptake within the lung and lymph nodes.⁹²

Associated Conditions

Since silicosis increases susceptibility to lung cancer and tuberculosis, it is essential to differentiate it from these conditions.⁶⁶ Fever, hemoptysis, and weight loss are indicators of lung cancer and tuberculosis, rather than chronic simple silicosis. Autoimmune diseases (including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and mixed connective tissue disease), chronic renal disease, and cor pulmonale are also associated with silica exposure.^93,94

Introduction

Asbestos has been used for various industrial purposes, due to its heat resistance, fibrous nature (which allows it to be spun), and durability. A naturally occurring hydrated magnesium silicate, asbestos is found in six forms: chrysotile, amosite, crocidolite, anthophyllite, actinolite and tremolite, belonging to the serpentine and amphibole groups. Chrysotile, a serpentine fiber, is the most common asbestos form used commercially. An asbestos fiber is defined by the U.S. Occupation Safety and Health Administration (OSHA) as a particle which is more than 5 μm in length, and has an aspect ratio (defined by its length divided by its diameter) equal to or greater than 3:1. The 2010 data suggest an annual use of around 2 million tons of asbestos around the world.⁹⁵ The World Health Organization estimates 11.3 million and 125 million workers in the United States and worldwide, respectively, have experienced asbestos exposure.⁹⁶ Unlike more than 50 countries, asbestos is not yet fully banned in the United States.

Occupations at Risk

Asbestos exposure occurs in (i) occupational, (ii) bystander, (iii) domestic, and (iv) environmental/residential settings. Naval shipbuilding and repair were a major source of occupational exposure during World War II since the pipes and boilers on ships were insulated with asbestos. The post–World War II urbanization fueled occupational exposure to insulation, roofing, tile, and floor covering in construction industry trades.⁹⁷ Mining, milling, transporting, and manufacturing continue to be other sources of occupational exposure. Bystander exposure occurs among people who work in close contact with people working directly with asbestos. Domestic exposure, also known as indirect exposure, occurs in household members as a result of the fiber-laden clothing brought home by asbestos workers. For example, wives are exposed during laundering of contaminated clothing.⁹⁸ Environmental and residential exposure consists of living around asbestos mills, mines, or industrial plants, as seen in Libby, Montana⁹⁹; or from local soil used for whitewashing houses, as seen in Greece and Turkey.¹⁰⁰

It is important to note that the duration and intensity of exposure plays an important role in the development of asbestos-related pulmonary disease. In addition, there is a significant latency period between the time of exposure and pathogenic manifestation of disease.

Pathogenesis

Following inhalation, the dimension of asbestos fibers determines whether these are cleared or deposited within the lung parenchyma. Short chrysotile fibers are cleared more readily than longer amphibole fibers. Fibers less than 3 μm in length are more efficiently phagocytosed by macrophages than longer fibers. Longer fibers accumulate in the lung parenchyma and are coated with iron and hemosiderin, becoming the core of asbestos bodies¹⁰¹ (see Fig. E1-3). In general, uncoated fibers predominate over coated fibers in an exposed individual. Ultimately, biologic potency and the ability to cause disease depend on the dose delivered (in the form of exposure duration and intensity) to the lung, fiber dimensions, fiber type, and retention time in the lung tissue.

Disease Phenotypes

Nonmalignant asbestos-related respiratory disease can be classified as parenchymal, airway predominant, and pleural diseases. Parenchymal lung disease includes asbestosis, a dust-related diffuse fibrosis phenotype. Airway-centric diseases include chronic bronchitis and emphysema phenotypes of COPD, and small airways diseases. Pleural disease includes circumferential pleural thickening or pleural plaques, diffuse pleural thickening, benign pleural effusion, and rounded atelectasis.

Asbestosis

Asbestosis is a chronic progressive diffuse fibrotic parenchymal lung disease that resembles IPF, caused by inhalation of excessive amounts of asbestos fibers. Clinically, the disease progresses slowly with a typical latency period of more than 20 years from first exposure to the onset of symptoms. The overall U.S. age-adjusted asbestosis death rate is estimated at 4.1 per million population per year, the rate for men being 35-fold higher than that for women.¹⁰² The rates for asbestosis increased from 1970 to 2000 and have decreased since 2004,¹⁰² likely reflecting a decrease in exposure levels.

Asbestosis starts in the region of the respiratory bronchiole and extends gradually outward to involve the lung acinus.¹⁰³ There is a predilection for peribronchiolar fibrosis and inflammatory reactions via macrophages and type II pneumocytes. Alveolar air spaces and segmental and subsegmental bronchioles can also be afflicted as the fibrosis begins to involve the interstitial tissue. Subpleural honeycombing can be seen. The disease continues to progress even after an individual is no longer exposed, and this progression may be related to cumulative exposure time. The degree of pulmonary fibrosis directly correlates with the degree of retention of fibers in the lung. Due to incomplete phagocytosis of these retained fibers, fibronectin is released along with other inflammatory mediators that recruit fibroblasts, leading to collagen deposition. Amphiboles (crocidolite and amosite) or mixture of amphibole and chrysotile are more prone to leading to asbestosis than chrysotile alone.¹⁰⁴ Cigarette smoking and exposure to asbestos have additive and independent effects on the risk for asbestosis.¹⁰⁵ Gene–environment interactions may further influence the development of asbestosis.^106,107

Asbestosis presents with radiographic changes of pulmonary fibrosis, with irregular reticular opacities, predominantly in the lower lobes and subpleural areas, which is consistent with UIP. Radiographic readings for pneumoconiosis use the ILO classification.¹⁰⁸ Subpleural curvilinear lines are an important CT finding favoring asbestosis.¹⁰⁹ The use of CT imaging may be useful under the following conditions: (1) a borderline finding of lung fibrosis, i.e., low ILO profusion scores of opacities of 0/1–1/0; (2) discrepancy between lung function findings of restriction and radiographs interpreted as normal; and (3) widespread pleural changes that severely hamper the radiographic visibility of lung parenchyma.¹⁰ The 2014 Helsinki criteria recommend the use of the international classification of HRCT to evaluate for asbestosis.^10,11

The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in IPF.¹⁰³ Apart from the presence of asbestos or asbestos bodies in the lung, asbestosis differs from IPF by the presence of relatively less inflammation, infrequent fibroblastic foci, and greater likelihood of mild fibrosis of the visceral pleura,¹⁰³ more frequent presence of pleural plaques, and a slower disease progression rate. Infrequent asbestos bodies do not necessarily exclude the diagnosis of asbestosis.¹⁰³ Biopsy is rarely necessary to make the diagnosis.

The backbone of diagnosing asbestosis rests on the 2003 criteria laid down by the American Thoracic Society which requires the presence of all of the following criteria⁴: (i) evidence of structural pathology consistent with asbestos-related disease as documented by imaging or histology; (ii) evidence of plausible causation by asbestos as documented by the occupational and environmental history, markers of exposure (usually pleural plaques), recovery of asbestos bodies, or other means in the setting of a plausible temporal relationship; (iii) exclusion of alternative plausible causes for the findings; and (iv) evidence of functional impairment as demonstrated by one or more of the following: signs and symptoms including crackles, change in ventilatory function, impaired gas exchange, inflammation, and impairment on exercise testing.

Airway-Centric Diseases

Asbestos exposure has long been known to be associated with an obstructive physiological abnormality (2004), characterized by reduction in the FEV₁/FVC ratio and reduced FEV₁. This effect begins in small airways, consistent with the known pathology of bronchiolitis in early asbestosis. Histologically, inflammation and airway fibrosis characterize asbestos-related small airways disease. These small airway lesions are the likely anatomic basis for airflow limitation in asbestos-exposed individuals. Radiographically, airflow abnormalities may also be associated with emphysema. As compared to controls, the prevalence of chronic bronchitis is significantly higher in asbestos-exposed workers, in both nonsmokers and smokers.^110,111

Pleural Diseases

• 1) Pleural plaques or circumscribed pleural thickening: Pleural plaques are often the first, the most frequent, and sometimes the only sign of asbestos exposure. Asbestos exposure is also the most common cause of bilateral pleural plaques. They rarely occur within less than 20 years from exposure and may be calcified. Plaques likely develop due to the deposition of fibers in the pleural space and subsequent inflammatory reaction by resident macrophages. Macroscopic features include smooth, white, and raised lesions with irregular borders and occasional calcification. Microscopic features include avascular, acellular collagen fibers with hyaline changes, which are arranged parallel to the pleural surface or in whorls. Plaques are often found incidentally on chest X-ray, and their presence can be confirmed with CT scans. Plaques are found mainly on the diaphragm and follow rib contours, in the posterolateral midzones. Usually asymptomatic, pleural plaques can be associated with neuropathic pain.¹¹² They may result in mild restrictive defects of uncertain clinical significance.¹¹³

• 2) Diffuse pleural thickening: Diffuse pleural thickening or extensive fibrosis of the visceral pleura may be asymptomatic initially but may cause a restrictive lung pattern and increased dyspnea in advanced disease.¹¹⁴

• 3) Rounded atelectasis: In this pleural reaction, also known as pseudotumor, the pleural surfaces fold on themselves and trap the underlying portion of the lung, giving it the appearance of a lung lesion. Although benign, the presence of rounded atelectasis may raise concerns for lung cancer in the minds of the treating physician.

• 4) Benign pleural effusions: Generally occurring less than 20 years postexposure and more common in younger patients less than 40-years old, these effusions are exudative, and occasionally hemorrhagic as well as eosinophil predominant.¹¹⁵ Clinical symptoms include fever, chest pain, pleural pain, and dyspnea. Such pleural effusions usually resolve spontaneously over a prolonged period of time.¹¹⁵

Associated Conditions

Associated conditions include lung cancer, mesothelioma, cor pulmonale, and hypoxic respiratory failure. Asbestosis increases the risk for lung cancer to a greater extent than asbestos exposure without asbestosis, and this risk is higher in smokers than nonsmokers.¹¹⁶ Although the plaques themselves are not precursors of malignant pleural disease, they indicate significant exposure, and therefore the patient is at increased risk of mesothelioma and lung cancer.¹¹⁷

Introduction

Uranium, a radioactive metal that occurs naturally in soil, rock, and water, is used in the production of nuclear armaments and nuclear power. Uranium mining reached a peak during the Cold War. Since the 1980s, uranium mining has decreased precipitously in the United States, but continues in Kazakhstan, Canada, and Australia, which produced 41%, 13%, and 12%, respectively, of the world’s uranium supply in 2018.^118,119

Occupations at Risk

Occupational exposure occurs primarily to uranium miners, but also in those with other position titles in industries that use uranium, such as millers and nuclear weapons workers.

Epidemiology

In the United States, uranium was mostly mined in the Colorado Plateau of the American Southwest, including the states of New Mexico, Colorado, Utah, and Arizona. Many mines were located in and around American Indian reservations, and as a result, uranium workers’ pneumoconiosis disproportionately affects American Indians.

Pathogenesis

The predominant injurious agent to the lung in uranium workers is believed to be alpha particles from inhaled radon progeny, decaying in or adjacent to lung tissues.^120,121 Although silica also probably contributes, the paucity of quartz crystals in the lung specimens from uranium miners suggests that silica may not be the primary pathogen.¹²¹ In animal studies, the fibrogenic effect of silica in the lung is enhanced by ionizing radiation.¹²² Chronic low-level inhalational exposure can also cause DNA mutation and damage from alpha radiation.

Disease Phenotypes

Uranium workers’ pneumoconiosis may present as dust-related diffuse pulmonary fibrosis or nodular lung disease.^{121,123–125} Chest X-rays of uranium workers in New Mexico predominantly demonstrate lower lobe predominant, irregular, small opacities.¹²⁴ Other studies demonstrate upper lobe predominant rounded opacities.¹²³ Changes of PMF have been described.¹²⁶ In addition, chronic bronchitis and the emphysema phenotypes of COPD are common.¹²⁷

Associated Conditions

Uranium workers may also be at increased risk for lung cancer^127,128 and atherosclerotic cardiovascular disease.¹²⁹

Introduction

Hard metal lung disease (HMLD) encompasses a collection of interstitial lung diseases caused by hard metals, such as cobalt and tungsten. Cobalt and tungsten have several industrial uses but not all have been known to cause HMLD. Cobalt and tungsten carbide are combined with each other to form cemented tungsten carbide, which is a hard substance used to manufacture tools for high-speed cutting, drilling, grinding, or polishing of other hard materials.¹³⁰ It is believed that cobalt rather than tungsten carbide is the agent responsible for HMLD.¹³⁰

Occupations at Risk

Populations at risk for HMLD include workers in the hard metal and bonded diamond tool industry.¹³¹ One profession at particular risk is diamond polishing.^132,133

Pathogenesis

The pathogenesis of HMLD is unclear. An immunologic mechanism is supported by its variable latency period, nonlinear dose-response relationship, pathological features, and the fact that systemic corticosteroids can reverse the course of the disease. Early disease is characterized by hyperplasia and metaplasia of the bronchial epithelium. If the exposure is chronic, the disease can progress to subacute alveolitis followed by chronic interstitial fibrosis.

Disease Phenotypes

Although hard metal exposure can cause work-related asthma and COPD, HMLD typically refers to a collection of interstitial lung diseases, including hypersensitivity pneumonitis (HP), obliterative bronchiolitis, nonspecific interstitial pneumonitis (NSIP), giant cell interstitial pneumonitis (GCIP), desquamative interstitial pneumonitis (DIP), and UIP.^131,134,135 A pathognomonic feature of HMLD is GCIP, which is characterized by the presence of cannibalistic multinucleated giant cells, seen in bronchoalveolar lavage fluid or on lung biopsy.¹³¹

Radiologic Features

Numerous radiographic patterns have been reported among patients with HMLD and are usually not diagnostic of this entity.¹³¹ Chest radiographs may be completely normal or show a nodular, reticular, or reticulonodular pattern. HRCT findings are similarly variable and may resemble NSIP, UIP, or HP patterns.^{131,136–138}

Management

Because HMLD may be reversible, it is important to identify the disease early and remove the affected worker from exposure to limit disease progression.¹³¹ Medical management is primarily symptomatic, although systemic corticosteroids may be helpful.¹⁵

Introduction

Man-made vitreous fibers (MMVF), also called man-made mineral fibers, or synthetic vitreous fibers, are a group of fibrous inorganic materials including rock, clay, slag, and glass. They are usually aluminum and calcium silicates not found in the nature. Examples include fiberglass, mineral wool (such as stone wool or slag wool), and refractory ceramic fibers. These fibers are used to reinforce building materials and as insulation against temperature and sound.

Epidemiology and Occupations at Risk

In 2001, an estimated 9 million tons per year of MMVF were produced worldwide.¹³⁹ Workers may be exposed in the manufacture, handling, use, removal, and disposal of these materials. Nonprofessionals performing home care and maintenance may also be exposed.

Pathogenesis/Mechanism of Toxicity

Fibers that dissolve poorly and are larger than 20 µm are difficult for lung macrophages to clear and are more likely to persist in workers’ lung tissue. Patients with impaired clearance, such as smokers, may be at greater risk for biopersistence.

Disease Phenotypes

The health effects of chronic MMVF exposure are debatable. Pleural plaques without interstitial abnormalities were described in a study of workers manufacturing refractory ceramic fibers.¹⁴⁰ In a comprehensive review in 1995, De Vuyst et al. highlighted the absence of firm evidence linking MMVF exposure with lung fibrosis.¹⁴¹ Since then, multiple case studies have demonstrated interstitial pneumonitis and fibrosis, on CT scans of the chest of exposed workers, with a relatively benign disease course.^{139,142–144} Another study has identified obliterative bronchiolitis in workers preparing fiberglass with styrene resins, exposing them to glass fiber–reinforced plastics.¹⁴⁵ It is unknown whether the fibers or an adulterant are a major determinant of pathogenicity.

Despite pneumoconiosis being one of the earliest recognized causes of lung diseases, workers in both traditional occupations and modern industries around the world continue to experience significant outbreaks of pneumoconiosis. A diagnosis of pneumoconiosis has a profound impact on the social and working life of the affected individual. Most pneumoconiosis are not curable but they are entirely preventable. Without strict dust control regulations, workers worldwide continue to develop this broad spectrum of diseases. Robust secondary prevention using screening and surveillance programs can protect individual workers from ongoing exposure and worsening disease. Increased and sustained adherence to regulations and other efforts to protect the health of workers engaged in dusty trades must be a top priority.