REVIEW URRENT C OPINION
Man-made mineral fibers and interstitial lung diseases Elizabeth Fireman
Purpose of review Manufactured (artificial) fibers represent an important and continuously growing volume among substitutes to natural fibers. A major proportion of the population in an industrialized society has been, is, or will be in contact with these fibers. The fibrous configuration of asbestos is well recognized as being an important parameter in toxicity, and now that of synthetic fibers is also suspected of inducing serious health effects on the respiratory system. There is an ongoing debate about the actual fibrogenic effect of these man-made mineral fibers (MMMFs) in humans. Recent findings Several case reports have demonstrated the biopersistance of MMMFs in the lung of workers who were exposed to rock wool or fiberglass for long periods of time and were diagnosed with interstitial pulmonary fibrosis. A 20-year follow up also identified refractory ceramic fibers in workers’ lung tissue, with significant association between cumulative fiber exposure and radiographic pleural changes. Newly emerging manmade fiber industries appear to induce new types of occupational diseases. Summary Exposure of workers in MMMFs production plants is correlated to high risk for developing pneumoconiosis. Large epidemiological studies are needed in order to determine dose metrics for risk assessment and management. Video abstract http://links.lww.com/COPM/A11 Keywords interstitial lung diseases, man-made mineral fibers
INTRODUCTION The first intimation that mineral fibers other than asbestos were biologically active essentially dates from the reports by Stanton and Wrench [1] and Pott and Friedrichs [2] that appeared in 1972. Those reviews looked at the occupational health effects of certain man-made and naturally occurring mineral fibers that had been identified between 1890 and 1935 and the precautions developed against them. The term man-made mineral fibers (MMMFs) is the generic name for a wide variety of manufactured fibrous materials that have a woolly consistency and are normally made of molten glass (glass wool), rock (rock wool) or slag (slag wool). The term does not include naturally occurring silicate fibers, such as asbestos or man-made organic fibers, such as nylon and rayon. MMMFs are typically classified into three types: continuous filament glass, mineral wool and refractory ceramic fibers (RCFs) [3,4 ]. &&
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Continuous filament glass fibers have uniform diameters between 3.5 and 25.0 mm and are typically thicker than mineral wool fibers, and are not considered inhalable. They are basically used to reinforce materials used in insulation, electronics and construction industries. The three classic mineral wools (rock, slag and glass) are masses of interlocking, disorganized fibers. Rock and slag wools were the first to be manufactured in the mid-nineteenth century, and
National Laboratory Service for ILD, The Institute of Pulmonary and Allergic Diseases, Tel-Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel Correspondence to Elizabeth Fireman, PhD, Institute of Pulmonary and Allergic Diseases, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel. Tel: +972 3 6973749; fax: +972 3 6947264; e-mail: [email protected] Curr Opin Pulm Med 2014, 20:194–198 DOI:10.1097/MCP.0000000000000035 Volume 20 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Man-made mineral fibers and interstitial lung diseases Fireman
KEY POINTS In 2002, it was estimated that 9 million tons/year of MMMFs were produced worldwide. Numerous workers have been, are, or will be exposed to these fibers. MMMFs have been considered much less biopersistent than asbestos fibers. Emerging data support a correlation between MMMFs and pulmonary fibrosis. Epidemiological studies on the fibrinogenic effects of MMMFs are urgently needed.
they are used for thermal and acoustic insulation, typically in buildings, vehicles and appliances. They are also used for inflammable materials and flameretardant protection. Fiberglass microfibers, which are glass wool fibers with a diameter smaller than 1 mm, merit special attention. They are used as highefficiency air filters, or in aerospace insulation in high-tech products. RCFs are a mixture of aluminum, silica and other refractory oxides. Their fibers have a diameter of 1.2–3.5 mm, and their longitude is variable. They were first commercialized between 1950 and 1960, making them relatively new compared with the other MMMFs that are used mainly for hightemperature thermal insulation requirements at the industrial level.
MAN-MADE MINERAL FIBERS HAZARDS Short-term health effects manifested as acute and, with lower frequency, chronically persisting symptoms involving the skin and upper respiratory mucosa have been documented among workers exposed to MMMFs [5,6]. However, it is the longterm effects, notably pulmonary fibrosis and respiratory (lung) cancer, which have mostly attracted attention in the last 10–15 years for a number of reasons. One reason is the size of the occupationally exposed populations which is, of course, related to the volume of the MMMFs production, that had been estimated to total about 46.105 tons worldwide in 1973 [7]. According to the International Agency for Research on Cancer (IARC) [8], an estimated 9 million tons of MMMFs were produced in over 100 factories worldwide in 2001. Another reason stems from the results of animal experiments that clearly showed MMMFs as being capable of inducing fibrosis [9]. Indeed, animal studies of pneumoconiosis induced by exposure to
mineral fibers by intratracheal instillation or inhalation have made a major contribution to our understanding of the underlying pathology of pulmonary fibrosis [10–12]. For toxicological purposes and in consideration of the European Union directives concerning protection of humans at work [13,14 ], it is important to distinguish between fibers that are themselves considered as substances that may be released into the atmosphere at any step of the manufacture or use of commercial products and fibers that contain products considered as preparations that may contain different types of fibers or other substances (resin, cement, other minerals). The latter should be defined according to their chemical composition, that is, glass, rock, slag or ceramic. Insofar as the precise mechanisms of fiber toxicity are not yet understood, the grouping of fibers of equivalent potential toxicity remains incomplete. Differences in toxicity of fibers of similar geometry are primarily related to biopersistence [15]. Biopersistence is defined as the total of all physical and chemical processes leading to clearance of fibers from the respiratory tract in vivo. The biopersistence of fibers deposited in the respiratory tract results from a combination of physiological clearance processes (mechanical translocation/removal) as well as physicochemical processes (chemical dissolution and leaching, mechanical breaking). Breakage of fibers may lead to a temporary increase of the numbers of fibers in the lung. Animal models have been used for experiments to test the toxicity and evaluate the biopersistence of MMMFs in the lung. One sheep model of pneumoconiosis compared the clearance rate, related pathology, chemical and morphological changes of three MMMFs compared with crocidolite asbestos fiber and found that the diameter of MMMFs decreased during the course of time, whereas the crocidolite fibers did not seem to show any change. After 2 years in the sheep tracheal lobe, ferruginous bodies were not found in all three MMMF groups but were substantial in the crocidolite group [16]. Another study using a Fischer 344/N rat model analyzed retention of fibers following inhalation of two fiberglass compositions (i.e., either rock wool or slag wool) and inhalation of 10 mg/m3 crocidolite asbestos at eight time points up to 1 year postexposure. The results demonstrated relatively low biological persistence of some man-made vitreous fibers (MMVFs) in the lung, which may explain why those MMVFs were not tumorigenic in rats, even after chronic exposure at high concentrations [17]. An in-vitro assay using a human monocytic cell line (U-937) was carried out in order to evaluate a
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&&
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Obstructive, occupational and environmental diseases
new manufactured rock wool fiber (HDN) biodegradation in an attempt to overcome bias in results due to species differences with respect to respirability, lung retention and mechanisms of responses [18]. Degradation was tested by surface alteration of the fibers detected by a scanning electron microscope and by the release of silicone from activated U-937 monocytes. The pattern of MMMF degradation by this in-vitro system was found to be a function of the fiber composition and time of exposure, in accordance with the results of the in-vivo study. Taken together, these results indicate that the fiber degradation by macrophage cells activated by Escherichia coli living cells is a valuable system for assessing the biopersistence of mineral fibers [18]. The available data on biopersistence in humans are too limited to arrive at any general conclusions about the biopersistence of all MMMFs in the human lung. Several laboratories worldwide have been involved in measuring fibers in human lung tissue for more than two decades, and Churg and Wright [19] reviewed the large body of data that had accumulated. The majority of the human data most relevant to biopersistence were obtained from analyses of fragments of lung parenchyma taken at autopsy of workers who had been exposed in the manufacturing industry, or samples of bronchoalveolar lavage (BAL) fluids. Fiber content was tested in biopsies of workers who had worked an average 11 years and died 12 years after leaving employment in 11 plants that produced fibrous glass and six plants that produced mineral wool [20]. The most notable finding was the absence of man-made vitreous silicate fibers from most workers’ lungs, from which it was concluded that the fibrous dust particles to which production workers had been exposed were either essentially nonrespirable or, more probably, did not survive the pulmonary environment [20]. Sebastien et al. [21] analyzed fibers recovered in BAL fluids obtained from seven workers employed in a ceramic fiber plant in France who were healthy and volunteered to undergo BAL. No precise information was reported on the chemical types of fibers produced. Both native and highly transformed (to element composition) ceramic fibers were detected. There was no relationship between the concentrations of fibers of either type and the duration of exposure. The transformation process was considered first to involve a coating of the ceramic fibers with ironcontaining granules, followed by a progressive dissolution of the structural elements, indicating that ceramic fibers may not be durable in the human lung. In contrast to those findings, a very recent publication demonstrated biopersistence of RCFs 196
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identified in human lung tissue in a 20-year follow up, with significant association between cumulative fiber exposure and radiographic pleural changes [22 ]. The RCFs within lung tissue comprised 14–100% of fibers that were 5 mm or more in length, and they were identified up to 20 years after RCFs exposure. The cumulative exposure of more than 63 to 110 and more than 110 fiber-months/cm3 was associated with radiographic pleural changes of 8.5 and 11.6%, respectively, among workers with no reported asbestos exposure. &&
MAN-MADE MINERAL FIBERS-INDUCED INTERSTITIAL LUNG DISEASES Animal studies of pneumoconiosis that had been induced by exposure to mineral fibers by intratracheal instillation or inhalation have made a major contribution to our understanding of the underlying pathology of pulmonary fibrosis. Mineral fibers deposited in the lung lead to the activation of alveolar macrophages. Alveolar macrophages, parenchymal cells and epithelial cells release proinflammatory cytokines, such as tumor necrosis factor, interleukin-1 (IL-1), IL-6 and others, which augment cellular inflammation. Release of oxidants and proteinases by these cells may lead to lung injury. Some growth factors signal interstitial fibroblasts to replicate and modulate production of connective tissue proteins. The accumulation of inflammatory cells, fibroblasts and connective tissue matrix leads to lung injury and angiogenesis, resulting in fibrosis and carcinoma [11]. Human studies need to answer the questions of whether prolonged exposure in an atmosphere containing fiberglass adversely affects pulmonary function, produces radiographic abnormalities and induces pulmonary fibrosis. These answers are elusive practically because of the minimal latent period for the development of fiber disease if it is analogous to asbestosis, and also many workers should have been exposed to asbestos to some degree too, as man-made fibers were manufactured in plants in which furnaces, retorts, ovens, and other facilities were insulated with asbestos. In a very comprehensive review by De Vuyst et al. [9] published in 1995, the authors stated that there is actually no evidence of a pneumoconiosis risk among exposed workers in glass, rock or slag wool production plants. They stated that this is probably because of the low respirable properties and the biopersistence of these fibers compared with asbestos. The possible role of ceramic fibers in the development of pleural plaques still needs to be delineated. There are no high-resolution computerized tomographic (CT) scan studies on large exposed Volume 20 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Man-made mineral fibers and interstitial lung diseases Fireman
populations. This imaging technique could produce some interesting observations and possibly reduce the inter-observer variability in International Labor Organization readings. However, new data that emerged over the past decade provided more evidence that demonstrated the adverse effect of the fibrinogenesis and biopersistence of MMMFs on the health of humans. Biopersistence of refractory ceramic fibers (RCFs) was identified in workers’ human lung tissue in a 20-year follow up, with significant association between cumulative fiber exposure and radiographic pleural changes [22 ]. Several case reports have clearly demonstrated the biopersistence of the fibers over a period of years and linked the exposure of workers to MMMFs in the development of pulmonary fibrosis. Takahashi et al. [23] reported a carpenter with an occupational history of glass fiber inhalation for 41 years during which he wore no protective device. His chest radiograph showed small nodular opacities in the lower lung fields, as well as multiple cystic lesions and low attenuation areas in the upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. Widespread depositions of small glass fibers (
Man-made mineral fibers and interstitial lung diseases Elizabeth Fireman
Purpose of review Manufactured (artificial) fibers represent an important and continuously growing volume among substitutes to natural fibers. A major proportion of the population in an industrialized society has been, is, or will be in contact with these fibers. The fibrous configuration of asbestos is well recognized as being an important parameter in toxicity, and now that of synthetic fibers is also suspected of inducing serious health effects on the respiratory system. There is an ongoing debate about the actual fibrogenic effect of these man-made mineral fibers (MMMFs) in humans. Recent findings Several case reports have demonstrated the biopersistance of MMMFs in the lung of workers who were exposed to rock wool or fiberglass for long periods of time and were diagnosed with interstitial pulmonary fibrosis. A 20-year follow up also identified refractory ceramic fibers in workers’ lung tissue, with significant association between cumulative fiber exposure and radiographic pleural changes. Newly emerging manmade fiber industries appear to induce new types of occupational diseases. Summary Exposure of workers in MMMFs production plants is correlated to high risk for developing pneumoconiosis. Large epidemiological studies are needed in order to determine dose metrics for risk assessment and management. Video abstract http://links.lww.com/COPM/A11 Keywords interstitial lung diseases, man-made mineral fibers
INTRODUCTION The first intimation that mineral fibers other than asbestos were biologically active essentially dates from the reports by Stanton and Wrench [1] and Pott and Friedrichs [2] that appeared in 1972. Those reviews looked at the occupational health effects of certain man-made and naturally occurring mineral fibers that had been identified between 1890 and 1935 and the precautions developed against them. The term man-made mineral fibers (MMMFs) is the generic name for a wide variety of manufactured fibrous materials that have a woolly consistency and are normally made of molten glass (glass wool), rock (rock wool) or slag (slag wool). The term does not include naturally occurring silicate fibers, such as asbestos or man-made organic fibers, such as nylon and rayon. MMMFs are typically classified into three types: continuous filament glass, mineral wool and refractory ceramic fibers (RCFs) [3,4 ]. &&
www.co-pulmonarymedicine.com
Continuous filament glass fibers have uniform diameters between 3.5 and 25.0 mm and are typically thicker than mineral wool fibers, and are not considered inhalable. They are basically used to reinforce materials used in insulation, electronics and construction industries. The three classic mineral wools (rock, slag and glass) are masses of interlocking, disorganized fibers. Rock and slag wools were the first to be manufactured in the mid-nineteenth century, and
National Laboratory Service for ILD, The Institute of Pulmonary and Allergic Diseases, Tel-Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel Correspondence to Elizabeth Fireman, PhD, Institute of Pulmonary and Allergic Diseases, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel. Tel: +972 3 6973749; fax: +972 3 6947264; e-mail: [email protected] Curr Opin Pulm Med 2014, 20:194–198 DOI:10.1097/MCP.0000000000000035 Volume 20 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Man-made mineral fibers and interstitial lung diseases Fireman
KEY POINTS In 2002, it was estimated that 9 million tons/year of MMMFs were produced worldwide. Numerous workers have been, are, or will be exposed to these fibers. MMMFs have been considered much less biopersistent than asbestos fibers. Emerging data support a correlation between MMMFs and pulmonary fibrosis. Epidemiological studies on the fibrinogenic effects of MMMFs are urgently needed.
they are used for thermal and acoustic insulation, typically in buildings, vehicles and appliances. They are also used for inflammable materials and flameretardant protection. Fiberglass microfibers, which are glass wool fibers with a diameter smaller than 1 mm, merit special attention. They are used as highefficiency air filters, or in aerospace insulation in high-tech products. RCFs are a mixture of aluminum, silica and other refractory oxides. Their fibers have a diameter of 1.2–3.5 mm, and their longitude is variable. They were first commercialized between 1950 and 1960, making them relatively new compared with the other MMMFs that are used mainly for hightemperature thermal insulation requirements at the industrial level.
MAN-MADE MINERAL FIBERS HAZARDS Short-term health effects manifested as acute and, with lower frequency, chronically persisting symptoms involving the skin and upper respiratory mucosa have been documented among workers exposed to MMMFs [5,6]. However, it is the longterm effects, notably pulmonary fibrosis and respiratory (lung) cancer, which have mostly attracted attention in the last 10–15 years for a number of reasons. One reason is the size of the occupationally exposed populations which is, of course, related to the volume of the MMMFs production, that had been estimated to total about 46.105 tons worldwide in 1973 [7]. According to the International Agency for Research on Cancer (IARC) [8], an estimated 9 million tons of MMMFs were produced in over 100 factories worldwide in 2001. Another reason stems from the results of animal experiments that clearly showed MMMFs as being capable of inducing fibrosis [9]. Indeed, animal studies of pneumoconiosis induced by exposure to
mineral fibers by intratracheal instillation or inhalation have made a major contribution to our understanding of the underlying pathology of pulmonary fibrosis [10–12]. For toxicological purposes and in consideration of the European Union directives concerning protection of humans at work [13,14 ], it is important to distinguish between fibers that are themselves considered as substances that may be released into the atmosphere at any step of the manufacture or use of commercial products and fibers that contain products considered as preparations that may contain different types of fibers or other substances (resin, cement, other minerals). The latter should be defined according to their chemical composition, that is, glass, rock, slag or ceramic. Insofar as the precise mechanisms of fiber toxicity are not yet understood, the grouping of fibers of equivalent potential toxicity remains incomplete. Differences in toxicity of fibers of similar geometry are primarily related to biopersistence [15]. Biopersistence is defined as the total of all physical and chemical processes leading to clearance of fibers from the respiratory tract in vivo. The biopersistence of fibers deposited in the respiratory tract results from a combination of physiological clearance processes (mechanical translocation/removal) as well as physicochemical processes (chemical dissolution and leaching, mechanical breaking). Breakage of fibers may lead to a temporary increase of the numbers of fibers in the lung. Animal models have been used for experiments to test the toxicity and evaluate the biopersistence of MMMFs in the lung. One sheep model of pneumoconiosis compared the clearance rate, related pathology, chemical and morphological changes of three MMMFs compared with crocidolite asbestos fiber and found that the diameter of MMMFs decreased during the course of time, whereas the crocidolite fibers did not seem to show any change. After 2 years in the sheep tracheal lobe, ferruginous bodies were not found in all three MMMF groups but were substantial in the crocidolite group [16]. Another study using a Fischer 344/N rat model analyzed retention of fibers following inhalation of two fiberglass compositions (i.e., either rock wool or slag wool) and inhalation of 10 mg/m3 crocidolite asbestos at eight time points up to 1 year postexposure. The results demonstrated relatively low biological persistence of some man-made vitreous fibers (MMVFs) in the lung, which may explain why those MMVFs were not tumorigenic in rats, even after chronic exposure at high concentrations [17]. An in-vitro assay using a human monocytic cell line (U-937) was carried out in order to evaluate a
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&&
www.co-pulmonarymedicine.com
195
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Obstructive, occupational and environmental diseases
new manufactured rock wool fiber (HDN) biodegradation in an attempt to overcome bias in results due to species differences with respect to respirability, lung retention and mechanisms of responses [18]. Degradation was tested by surface alteration of the fibers detected by a scanning electron microscope and by the release of silicone from activated U-937 monocytes. The pattern of MMMF degradation by this in-vitro system was found to be a function of the fiber composition and time of exposure, in accordance with the results of the in-vivo study. Taken together, these results indicate that the fiber degradation by macrophage cells activated by Escherichia coli living cells is a valuable system for assessing the biopersistence of mineral fibers [18]. The available data on biopersistence in humans are too limited to arrive at any general conclusions about the biopersistence of all MMMFs in the human lung. Several laboratories worldwide have been involved in measuring fibers in human lung tissue for more than two decades, and Churg and Wright [19] reviewed the large body of data that had accumulated. The majority of the human data most relevant to biopersistence were obtained from analyses of fragments of lung parenchyma taken at autopsy of workers who had been exposed in the manufacturing industry, or samples of bronchoalveolar lavage (BAL) fluids. Fiber content was tested in biopsies of workers who had worked an average 11 years and died 12 years after leaving employment in 11 plants that produced fibrous glass and six plants that produced mineral wool [20]. The most notable finding was the absence of man-made vitreous silicate fibers from most workers’ lungs, from which it was concluded that the fibrous dust particles to which production workers had been exposed were either essentially nonrespirable or, more probably, did not survive the pulmonary environment [20]. Sebastien et al. [21] analyzed fibers recovered in BAL fluids obtained from seven workers employed in a ceramic fiber plant in France who were healthy and volunteered to undergo BAL. No precise information was reported on the chemical types of fibers produced. Both native and highly transformed (to element composition) ceramic fibers were detected. There was no relationship between the concentrations of fibers of either type and the duration of exposure. The transformation process was considered first to involve a coating of the ceramic fibers with ironcontaining granules, followed by a progressive dissolution of the structural elements, indicating that ceramic fibers may not be durable in the human lung. In contrast to those findings, a very recent publication demonstrated biopersistence of RCFs 196
www.co-pulmonarymedicine.com
identified in human lung tissue in a 20-year follow up, with significant association between cumulative fiber exposure and radiographic pleural changes [22 ]. The RCFs within lung tissue comprised 14–100% of fibers that were 5 mm or more in length, and they were identified up to 20 years after RCFs exposure. The cumulative exposure of more than 63 to 110 and more than 110 fiber-months/cm3 was associated with radiographic pleural changes of 8.5 and 11.6%, respectively, among workers with no reported asbestos exposure. &&
MAN-MADE MINERAL FIBERS-INDUCED INTERSTITIAL LUNG DISEASES Animal studies of pneumoconiosis that had been induced by exposure to mineral fibers by intratracheal instillation or inhalation have made a major contribution to our understanding of the underlying pathology of pulmonary fibrosis. Mineral fibers deposited in the lung lead to the activation of alveolar macrophages. Alveolar macrophages, parenchymal cells and epithelial cells release proinflammatory cytokines, such as tumor necrosis factor, interleukin-1 (IL-1), IL-6 and others, which augment cellular inflammation. Release of oxidants and proteinases by these cells may lead to lung injury. Some growth factors signal interstitial fibroblasts to replicate and modulate production of connective tissue proteins. The accumulation of inflammatory cells, fibroblasts and connective tissue matrix leads to lung injury and angiogenesis, resulting in fibrosis and carcinoma [11]. Human studies need to answer the questions of whether prolonged exposure in an atmosphere containing fiberglass adversely affects pulmonary function, produces radiographic abnormalities and induces pulmonary fibrosis. These answers are elusive practically because of the minimal latent period for the development of fiber disease if it is analogous to asbestosis, and also many workers should have been exposed to asbestos to some degree too, as man-made fibers were manufactured in plants in which furnaces, retorts, ovens, and other facilities were insulated with asbestos. In a very comprehensive review by De Vuyst et al. [9] published in 1995, the authors stated that there is actually no evidence of a pneumoconiosis risk among exposed workers in glass, rock or slag wool production plants. They stated that this is probably because of the low respirable properties and the biopersistence of these fibers compared with asbestos. The possible role of ceramic fibers in the development of pleural plaques still needs to be delineated. There are no high-resolution computerized tomographic (CT) scan studies on large exposed Volume 20 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Man-made mineral fibers and interstitial lung diseases Fireman
populations. This imaging technique could produce some interesting observations and possibly reduce the inter-observer variability in International Labor Organization readings. However, new data that emerged over the past decade provided more evidence that demonstrated the adverse effect of the fibrinogenesis and biopersistence of MMMFs on the health of humans. Biopersistence of refractory ceramic fibers (RCFs) was identified in workers’ human lung tissue in a 20-year follow up, with significant association between cumulative fiber exposure and radiographic pleural changes [22 ]. Several case reports have clearly demonstrated the biopersistence of the fibers over a period of years and linked the exposure of workers to MMMFs in the development of pulmonary fibrosis. Takahashi et al. [23] reported a carpenter with an occupational history of glass fiber inhalation for 41 years during which he wore no protective device. His chest radiograph showed small nodular opacities in the lower lung fields, as well as multiple cystic lesions and low attenuation areas in the upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. Widespread depositions of small glass fibers (
