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Asbestosis
Abstract
The term pneumoconiosis dates to Zenker’s 1866 description of pulmonary disease processes related to the inhalation of dusts [1]. As some dust, including asbestos fibers, may be found in the lungs of virtually all adults from the general population, pneumoconiosis now refers to the accumulation of excessive amounts of dust in the parenchyma of the lung and the pathologic response to its presence [2]. Asbestosis, the form of pneumoconiosis related to excessive amounts of asbestos fibers in the substance of the lung, is the prototype of diseases caused by inhalation of mineral fibers. Asbestos is a commercial, legal, and regulatory term, rather than a strictly mineralogical one, that encompasses a group of naturally occurring fibrous silicates whose differing physicochemical attributes confer a spectrum of pathologic properties upon their inhalation and deposition into the lung. Much has been learned from experimental models about the pathogenesis of asbestos-induced lung injury, which is reviewed in detail in Chap. 10. The reader is directed to Chap. 3 for a discussion of asbestos bodies, the histologic emblem of asbestos exposure, and a requisite component of the pathologic diagnosis of asbestosis. Chapter 11 discusses the methodology and results of quantitative tissue analysis for asbestosis, other asbestos-related diseases, as well as normal and disease control populations. The present chapter describes the morphologic features of asbestosis and relates them to the clinical and radiographic features of the disease.
... This judgment was restated in an updated version of the risk-evaluation report issued by WHO in 2014. The health risk of chrysotile is controversial; some researchers argue that it is less dangerous than amphiboles and that low levels of inhalation do not necessarily present a health risk (Sporn and Roggli, 2004;Bernstein, 2014), although prolonged exposure can lead to disease. However, in the aforementioned report, WHO stated clear conclusions from the IARC: with respect to cancer of the lungs and mesothelioma, there is sufficient evidence of carcinogenicity in humans for all forms of asbestos, including chrysotile. ...
This chapter outlines the ‘whole picture’ of this book. The concept of nanosized tubular clay minerals is introduced, and the general information about the past and present studies on typical nanosized tubular clay minerals, halloysite and imogolite, is briefly reviewed. In addition, the main content of each chapter of this book is forenoticed.
The diagnosis of asbestosis requires different criteria depending on whether it is in a clinical or medical/legal setting. In the latter context, only when a “diffuse interstitial fibrosis associated to asbestos bodies (ABs)” is present, it can be said to be asbestosis. Considering the medical/legal setting, the diagnosis must be certain and proven. Unfortunately, it is often difficult to identify ABs by light microscopy (LM), but this does not mean that the diagnosis should be clinically excluded. Other parameters are important, such as working history and/or diagnostic imaging. In addition to LM, normally used for diagnosis, there are other techniques, e.g.: scanning electron microscopy with attached microanalysis microprobe (SEM/EDS), but they require tissue digestion and higher cost. A new approach with micro-Raman spectroscopy and SEM/EDS techniques is able to analyse histological sections without other manipulations that could interfere with analysis of asbestos fibres. In this work, we propose an algorithm for asbestosis diagnosis, especially in the forensic medical field, demonstrating the importance of close collaboration between multiple professionals.
Objectives
In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose–response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks.
Methods
Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause‐specific (CS) Cox‐regression models were used to evaluate the dose‐exposure relationship between asbestosis mortality and the time‐dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death.
Results
The cohort included 12,963 asbestos cement workers. During the follow‐up period (1960−2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose–response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL‐years. Lung cancer and circulatory diseases were the main competing causes of death.
Conclusions
Asbestos exposure among Italian asbestos‐cement workers has led to a very high number of deaths from asbestosis and asbestos‐related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.
Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.
While many terms are usually associated with suspended matter in the air, airborne particles or particulate matter (PM) generally refer to solid particles that may be composed of multiple phases (e.g., solids, liquid droplets, etc.). Airborne particles vary extensively in physical and chemical characteristics; their sizes can vary from tens of micrometers, that is, slightly smaller than beach sand or hair, to tens of nanometers. Solid airborne particles have been historically related to a wide range of occupational diseases such as various types of pneumoconioses (e.g., “black lung disease”), as well as less occupationally targeted respiratory illnesses such as acute respiratory irritation, asthma, or lung cancer. This chapter outlines airborne particles, its adverse health effects to workers in ( 1 ) areas with targeted production of particles and ( 2 ) in areas where exposure to ambient pollution is inevitable. This chapter presents metrics, techniques, exposure assessments, and biomarkers used for particulate measurements and routine monitoring. Also summarized in this chapter: its toxicity, mechanisms of attack, and carcinogenicity. Lastly, it tabulates existing standards both for the ambient and workplace and outlined some of the existing removal and control technologies. The ubiquity of airborne particles—from outdoor jobs, such as construction and firefighting, to indoor occupations, such as healthcare and custodial jobs, make it a central issue that is necessary to be addressed in any workplace area.
The use of electrospun meshes has been proposed as highly efficient protective equipment to prevent respiratory infections. Those infections can result from the activity of micro-organisms and other small dust particles, such as those resulting from air pollution, that impair the respiratory tract, induce cellular damage and compromise breathing capacity. Therefore, electrospun meshes can contribute to promoting air-breathing quality and controlling the spread of such epidemic-disrupting agents due to their intrinsic characteristics, namely, low pore size, and high porosity and surface area. In this review, the mechanisms behind the pathogenesis of several stressors of the respiratory system are covered as well as the strategies adopted to inhibit their action. The main goal is to discuss the performance of antimicrobial electrospun nanofibers by comparing the results already reported in the literature. Further, the main aspects of the certification of filtering systems are highlighted, and the expected technology developments in the industry are also discussed.
Introduction
The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.
Methods
We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).
Results
Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.
Conclusions
We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.
Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.
Asbestosis is diagnosed with a combination of historical, clinical and radiological findings in the absence of another cause. Histology is required when uncertainty exists, with lung biopsy via VATs being gold standard. Transbronchial cryobiopsy is becoming increasingly popular for diagnosing interstitial lung disease and may provide sufficient lung sample to demonstrate asbestosis. A 73 year old man presented with dyspnoea on a background of rheumatoid arthritis, previous methotrexate use and asbestos exposure. Examination revealed fine crackles in the mid and lower zones bilaterally without signs of pulmonary hypertension. The presence of pleural plaques and basal interstitial reticulation on HRCT was suggestive of asbestosis but histology was required to differentiate this from rheumatoid or methotrexate associated ILD. Samples of lung tissue were obtained via transbronchial cryobiopsy, demonstrating fibrosis and asbestos fibres consistent with asbestosis. Transbronchial cryobiopsy appears effective in obtaining sufficient parenchymal lung samples to diagnose asbestosis when clinical uncertainty exists. Transbronchial cryobiopsy appears to be an effective way of obtaining parenchymal lung samples of sufficient size to diagnose asbestosis when clinical uncertainty exists.
Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.
Unlabelled:
Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms.
Differential diagnosis:
IDIOPATHIC PULMONARY FIBROSIS: The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis.
Differential diagnosis:
RESPIRATORY BRONCHIOLITIS: Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis.
Role of asbestos bodies:
Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5- mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests.
Role of fiber analysis:
Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.
To describe the demographic, geographic, and occupational distribution of asbestosis mortality in the United States during 1970-2004, we identified a total of 25,413 asbestosis deaths. We calculated national, state, and county death rates, age-adjusted to the 2000 U.S. standard population. We also calculated industry- and occupation-specific proportionate mortality ratios (PMRs), adjusted for age, sex, and race, and corresponding confidence intervals (CIs) using available data. The overall U.S. age-adjusted asbestosis death rate was 4.1 per million population per year; the rate for males (10.4) was nearly 35-fold higher than that for females (0.3). It increased significantly from 0.6 to 6.9 per million population from 1970 to 2000 (p<0.001), and then declined to 6.3 in 2004 (p=0.014). High asbestosis death rates occurred predominantly, though not exclusively, in coastal areas. Industries with highest PMRs included ship and boat building and repairing (18.5; 95% CI 16.3-20.9) and miscellaneous nonmetallic mineral and stone products (15.9; 95% CI 13.0-19.5). Occupations with highest PMRs included insulation workers (109.2; 95% CI 93.8-127.2) and boilermakers (21.3; 95% CI 17.0-26.6).
Five groups of rats were treated by inhalation for 12 months, with the U.I.C.C. preparations of the 3 main commercially used asbestos types, chrysotile, crocidolite and amosite. The experiment was designed so that the effects of both fibre mass and fibre number could be examined. The results indicated that chrysotile dust caused far more lung fibrosis than either amphibole type even when the fibre numbers in the dust clouds were similar. All malignant pulmonary neoplasms found during this study occurred in animals treated with chrysotile. The fibre-number calculations used for the generation of dust clouds were evaluated using the parameters recommended by the Health and Safety Executive in 1976, by which all fibres over 5 microgram long are counted using a phase-contrast light microscopy. When fibre-length distributions were calculated using a scanning electron microscope, however, it was found that the chrysotile clouds used in this study contained many more fibres over 20 microgram long than either of the amphibole clouds. The results, therefore, support previous suggestions that long asbestos fibres are more dangerous than short. They also indicate that neither a single mass standard, nor the present fibre-number standards are satisfactory.
Images
Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Figs. 9 and 10
The US Navy's Asbestos Medical Surveillance Program monitors civilian and military employees with current or historical exposure to asbestos. The prevalence of definite radiologic parenchymal abnormalities (ILO category greater than or equal to 1/0) was 3.10 percent for 32,233 smokers vs 1.09 percent for 13,414 nonsmokers. The age-adjusted prevalence ratio was 2.23. The difference in prevalence between smokers and nonsmokers persisted in all age groups studied and was greatest among the oldest employees. These findings in a large population suggest that parenchymal opacifications alone will not reliably differentiate between the impacts of asbestos exposure and smoking in patients who face both risks.
Context.—Asbestosis is one of many forms of diffuse interstitial pulmonary fibrosis. Its histologic diagnosis rests on the pattern of fibrosis and the presence of asbestos bodies by light microscopy in lung biopsies.
Objective.—To determine the asbestos fiber burden in patients with diffuse pulmonary fibrosis (DPF) who had a history of asbestos exposure, but whose biopsies did not meet established criteria for asbestosis, and compare it with the fiber burden in confirmed asbestosis cases.
Design.—Fiber burden analysis was performed using scanning electron microscopy and energy-dispersive x-ray analysis of lung parenchyma from 86 patients with DPF and 163 patients with asbestosis. The correlation of the number of asbestos fibers found for a quantitative degree of fibrosis was analyzed.
Results.—The fibrosis scores of the asbestosis cases correlated best with the number of uncoated commercial amphibole fibers. Seven DPF cases fell within the 95% interval of asbestos body count by light microscopy and 3 cases within that of the total commercial amphibole fiber count.
Conclusions.—Strict histologic criteria are useful for positive identification of asbestosis among cases of advanced pulmonary fibrosis. Few DPF patients with history of asbestos exposure whose biopsies did not meet the criteria for asbestosis may have asbestos fiber counts in the range seen in asbestosis, and fiber type identification by scanning electron microscopy with energy-dispersive x-ray analysis should be considered in these rare instances to avoid false-positive and false-negative diagnoses of asbestosis.
Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms.
Differential Diagnosis: Idiopathic Pulmonary Fibrosis
The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis.
Differential Diagnosis: Respiratory Bronchiolitis
Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis.
Role of Asbestos Bodies
Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5-μm-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests.
Role of Fiber Analysis
Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.
Ascertainment, through 7,400 pathologists, of all fatal malignant mesothelial tumors in Canada (1960–75) and the U.S.A. (1972) gave a total of 668 cases (272 in 1972). In Canada, the annual number of male cases rose from about 17 in 1966 to 25 in 1972 but the number of female cases remained fairly steady at a much lower level. The annual incidence in North America in 972 was estimated at 2.8 per million males and 0.7 per million females aged 15 years and over. Occupational histories were obtained “blind” for 480 of the 557 cases through 1972, and their matched controls; relative risks were as follows: insulation work, 46.0, asbestos production and manufacture, 6.1, heating trades (other than insulation) 4.4. For nearly half the male cases and for about 5% of female cases, the tumor could be attributed to occupational exposure to asbestos, of which a fifth were in shipyards. No indication was found of other possible causes (including man-made mineral fibers, tobacco smoking, or residence near zeolite deposits). Four subjects were men who had been employed in Quebec chrysotile mines and 3 were children of employees, but no other subject had lived in the mining area. The findings remain consistent with a much greater mesothelioma-producing potential for crocidolite and amosite than for chrysotile; however, further studies of factory workers exposed to chrysotile only are needed to confirm this. Mineral fiber analysis of lung tissue from patients and controls is in progress.
Introduction Occupational lung disease is the most significant form of work-related illness in the United States in terms of its severity, frequency and cost to society. The US Department of Labor reported the occurrence of some 4.1 million workplace injuries and illnesses in 2006, including 17 700 respiratory ailments in private industry alone and an incidence of non-fatal occupational respiratory illness of 1.9 cases per 10 000 full-time workers. Occupational lung diseases result in one of the most significant causes of lost work productivity, with the highest rate of days away from work due to respiratory illness sustained by the mining industry. Occupational lung diseases are the third most prevalent (246 per 100 000 population) in the European Union, also with the highest proportion found in the mining industry. Technological advances in construction have led to new groups of at-risk workers in addition to the traditional occupations in mining and quarry work. Global estimates of disability and disease resultant from occupational exposure to airborne particulates also include 386 000 deaths from pneumoconiosis, asthma and other chronic obstructive lung diseases. The toll that occupational lung diseases exact upon society is reflected in estimated direct and indirect costs that number in the billions of dollars. Occupational lung diseases cause significant morbidity, which usually lacks curative medical intervention at the time of presentation, apart from jobsite or occupation modification. Stringent oversight of workplace conditions and permissible exposures on the part of governments and regulatory agencies, along with the retention of occupational health physicians on the part of larger firms, will hopefully mitigate the development of severe disease in the future. © Cambridge University Press 2013 and The Estate of the late Herbert Spencer 2013 and The McGraw-Hill Companies Inc. 1962, 1968, 1977, 1985, 1996.
Virtually all therapies of modern medicine carry the potential for harm. Fortunately, the potential is usually low and the consequences are mild. Nevertheless, iatrogenic disease is common and can result in the death of patients. For example, it is estimated that the incidence of adverse drug reactions most likely lies between 10% and 20% but may range as high as 28%.1 Drug reactions cause between 2.9% and 6.2% of all hospital admissions and as many as 0.31% of all hospital deaths.1,2 A substantial fraction of drug reactions involve the respiratory system. Radiation therapy is also associated with adverse effects. Estimates of radiation pneumonitis range from 5% to 20% for patients given tumoricidal doses of thoracic radiation.3–5
Dail and Hammar's Pulmonary Pathology has established itself as the definitive reference in the field. This third edition is now a two-volume, full color text and has been thoroughly updated to cover newly recognized entities and the latest advances in molecular diagnostic techniques. It is abundantly illustrated with more than 2,000 illustrations in total, 1,900 of which are in full color. This outstanding contribution to pathology literature is a must-have for the library of every surgical and pulmonary pathologist. It has set the standard for which all other pathology texts strive to achieve. This first volume focuses on Non-neoplastic lung diseases, and Volume II covers Neoplastic Lung Diseases. New chapters include information on the pathology of small airways disease; forensic lung pathology; molecular genetics of lung and pleural neoplasms and pre-invasive disease. This new edition also includes two chapters devoted to molecular pathology that are a compendium of information on the molecular pathology of lung tumors as well as a primer on basic molecular pathology. © 2008 Springer Science+Business Media, LLC. All rights reserved.
Dail and Hammar's Pulmonary Pathology has established itself as the definitive reference in the field. This third edition is now a two-volume, full color text led by Dr. Tomashefksi, as Editor-in-Chief and Drs. Cagle, Farver, and Fraire as Associate Editors. The new editorial board has continued to build upon the excellence Dail and Hammar achieved in the previous editions by reorganizing, expanding and substantially revising the text. This authoritative reference work has been thoroughly updated to cover newly recognized entities and the latest advances in molecular diagnostic techniques. Abundantly illustrated with more than 2000 full color illustrations, this outstanding contribution to pathology literature is a must-have for the library of every surgical and pulmonary pathologist. It has set the standard for which all other pathology texts strive to achieve. From the reviews of the Second Edition: Pulmonary Pathology deserves the stature it has acquired of late as the preeminent clinicopathologic textbook on diseases of the lung. American Journal of Clinical Pathology. © 2008 Springer Science+Business Media, LLC. All rights reserved.
A proposal is made for the grading of pulmonary fibrosis, based on the extent of lung involvement and on the severity of the fibrosis. No diagnosis of any particular cause is involved, thus the grading may be compared directly with the results of respiratory and radiographic tests. It is proposed that a necessary criterion for the diagnosis of asbestosis be the presence of fibrosis with included asbestos bodies or fibres. However, it is recognised that while the grading of pulmonary fibrosis would thus become internationally comparable, the diagnosis of asbestosis may still require different decisions for different circumstances.
Sets forth a model approach to the consideration of diseases induced by environmental agents. Proceeding systematically from the extraction and processing of the mineral, it goes on to review the various manufacturing processes of asbestos and opportunities for exposure; its distribution in the environment; the etiology, prevalence, and clinical features of the resultant diseases; the cellular mechanisms of pathogenesis; and the various legal and engineering procedures involved in prevention and control. Criteria for establishing cause-and-effect relationships of a presumptive agent are developed, and the etiology of four pathogenic processes established, namely parenchymal asbestosis, pleural asbestosis, mesothelioma, and asbestos-associated carcinoma. -after Author
This document has focused on clinically detectable interstitial fibrosis due to asbestos exposure. While direct examination of lung tissue is the most reliable method of diagnosis, this is rarely indicated in the assessment of workers for compensation purposes. Open lung biopsy is indicated in our opinion only when a clear health, rather than financial, benefit is likely to be provided. In the absence of pathologic examination of lung tissue, the diagnosis of asbestosis is a judgement based on a careful consideration of all relevant clinical findings. In our opinion, it is necessary that there be: 1. A reliable history of exposure. 2. An appropriate time interval between exposure and detection. Furthermore, we regard the following clinical criteria to be of recognized value: 1. Chest roentgenographic evidence of type 's', 't', 'u', small irregular opacifications of a profusion of 1/1 or greater; 2. A restrictive pattern of lung impairment with a forced vital capacity below the lower limit of normal; 3. A diffusing capacity below the lower limit of normal; 4. Bilateral late or pan inspiratory crackles at the posterior lung bases not cleared by cough. Of these, the findings on the chest roentgenogram are the most important. When this criteria is not met, considerable caution is warranted. The specificity of the above criteria increases with increasing numbers of positive criteria. As in all clinical judgments, confounding variables, such as the presence of other clinical conditions that affect these criteria, should be evaluated. It is possible that interstitial fibrosis may be present even though none of these criteria are satisfied, but, in our opinion, in these circumstances the clinical diagnosis cannot be made.
Pulmonary emphysema is among the most prevalent of all diseases. On the basis of examination of properly inflation-fixed lungs from consecutive autopsy series, it is present in at least one-third of the adult male population and in half or more of those men who smoke.1-5 This high prevalence is partly the result of the gradual evolution and progression of the lesions, which on average probably take some 30 or more years from the asymptomatic onset to the final lethal episode of respiratory failure. The prolonged course also gives many individuals the opportunity to die of other diseases so that the death rate from emphysema is far lower than the prevalence rate. Therefore, the major societal impact of the disease results not so much from total prevalence or deaths, as from the many years of disability and loss of productivity experienced by the many cases who become symptomatic in their late forties and survive with impairment throughout their fifties and sixties. The disease is less common in women, but the incidence in women has increased in recent years.5
Fig. 24-1
The regression of the correlation between age at death and percentage of lung involvement by centrilobular emphysema, detemined by point-counting, in the 173 autopsies of smokers who had the disease. The slope represents progression of the disease at the rate of 7% per 10 years. The correlation coefficient is .27 and the probability that this trend might have occurred by. chance is less than .001. The equation for the regression line is: Emphysema extent = .69 × age — 13.2. Values in parentheses represent number of cases seen in each 10-year age group. Horizontal bars represent average extent of emphysema per group.
To the Editor: The Medical Progress article by Mossman and Gee (June 29 issue)¹ was a well-documented review of asbestos-related diseases. In two respects, however, the review may add to the controversies surrounding the management of asbestos-related risks. First, the review appears to have understated the problem of asbestosis in the United States. Of the workers most heavily exposed to asbestos in the United States, 75 to 80 percent were employed in the construction trades, including asbestos insulators, boilermakers, and sheet-metal workers.² These blue-collar tradespeople were exposed to asbestos in the 1940s, 1950s, and 1960s with little or no warning.
Silicosis, a disease of historical importance, continues to occur cryptically today. Its pathogenesis is under ongoing study as new concepts of pathobiology evolve. In this article, the gross and microscopic features of the disease in the lungs and the lesions in lymph nodes and other viscera are described. These tissue changes are then discussed in the context of clinical disease and other possible or established complications of silica exposure (ie, scleroderma and rheumatoid arthritis, glomerulonephritis, and bronchogenic carcinoma). Silicates are members of a large family of common minerals, some of which have commercial importance. Silicates are less fibrogenic than silica when inhaled into the lungs, but cause characteristic lesions after heavy prolonged exposure. The features of these disease conditions are described herein. Various aspects of the mineralogy and tissue diagnosis of silicosis and lung disease due to silicates are reviewed. An overview of contemporary regulatory considerations is provided.
Study objectives
To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis.
Design
A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer.
Results
Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or exsmokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity.
Conclusions
Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.
The term pneumoconiosis, originally coined by Zenker,1 literally means dust in the lung. Because various types of dust can be found in the lungs of virtually all adults, this term
has come to mean the accumulation of abnormal amounts of dust in the lungs and the local pathologic response to this dust.
A great variety of dust particles have been identified, which, when inhaled in sufficient amounts, are capable of producing
disease in humans. The sources of these particles are diverse, ranging from occupational to environmental exposures. Factors
important in determining the pathologic response to a given dust exposure include the number, size, and physicochemical properties
of the inhaled particles; the route and efficiency of the clearance of particles from the respiratory tract; the nature and
intensity of the host’s inflammatory response to the particles deposited in the lung; the duration of the exposure and interval
since initial exposure; and the interaction between the inhaled particles from multiple sources and other environmental pollutants
such as cigarette smoke.
The glutathione S-transferases (GSTs) catalyze the conjugation of a wide variety of reactive, electrophilic substrates with glutathione, facilitating their excretion. There is also evidence that GSTs can catalyze glutathione conjugation of lipid radicals as well as act in the generation of leukotriene inflammatory mediators. Studying construction carpenters screened for the presence of asbestos-related diseases, we have previously reported that the constitutional deletion of GSTM1 (the gene coding for glutathione S-transferase class mu) is associated with an increased risk of asbestos-related interstitial lung disease, measured radiographically. In the current work, we have further studied this group of workers, investigating the distribution of a novel deletion polymorphism in the newly described GSTT1 gene, that codes for the GST class theta enzyme. A total of 666 carpenters were studied, and 124 (19%) had the deleted genotype. There was no association between the GSTT1 deletion and the radiographic diagnosis of either asbestos-related pleural or parenchymal disease. The GSTM1 deletion remained associated with the presence of x-ray evidence of asbestosis after adjustment for GSTT1 genotype. The GSTM1 null genotype was also associated with a family history of any malignancy. These data suggest that the association of polymorphic GSTs with asbestos-induced radiographic changes is specific for substrates of the GST class mu. Am. J. Ind. Med. 31:274–279, 1997. © 1997 Wiley-Liss, Inc.
Immunoblastic lymphadenopathy was diagnosed in a 71-year-old white man who had weakness, with weight loss, fever, cough, and generalized lymphadenopathy. The patient had a long occupational history of shipyard work. Diagnosis of asbestosis was made clinically by chest x-ray, and ferruginous bodies were found in the lung at autopsy. Recent reports have suggested a possible association between asbestos exposure and lymphoproliferative neoplasms. Chronic antigenic stimulation by asbestos could predispose one to the immunoproliferative disorder seen in this patient or be responsible for it. The possible significance of this relationship, previously unreported, is discussed for future consideration.
Glutathione S-transferase (GST) isozymes of human lung have been purified, characterized, quantitated, and, based on their structural and immunological profiles, identified with their respective classes. The π-, μ-, and α-class GSTs represented 94, 3, and 3% activities of total human lung GSTs toward CDNB, respectively, and 60, 10, and 30% of total GST protein, respectively. Both the μ- and the α-class GSTs of human lung exhibited heterogeneity. The two μ-class GSTs of human lung had pI values of 6.5 and 6.25 and were differentially expressed in humans. Significant differences were seen between the kinetic properties of these two isozymes and also between the lung and liver μ-class GSTs. The α-class GST isozymes of lung resolved into three peaks during isoelectric focusing corresponding to pI values of 9.2, 8.95, and 8.8. All three α-class GSTs isozymes had blocked N-termini and were immunologically similar to human liver α-class GSTs. Peptide fingerprints generated by SV-8 protease digestion and CNBr cleavage indicated minor structural differences between the liver and the lung α-class GSTs. The three α-class GSTs of lung expressed glutathione peroxidase activities toward the hydroperoxides of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol, with Km values in the range of 22 to 87 μm and Vmax values in the range of 67–120 mol/mol/ min, indicating the involvement of the α-class GSTs in the protection mechanisms against peroxidation. All three classes of lung GSTs expressed activities toward leukotriene A4 methyl ester and epoxy stearic acid but the μ-class GSTs had relatively higher activities toward these substrates.
Asbestosis is one of many forms of diffuse interstitial pulmonary fibrosis. Its histologic diagnosis rests on the pattern of fibrosis and the presence of asbestos bodies by light microscopy in lung biopsies.
To determine the asbestos fiber burden in patients with diffuse pulmonary fibrosis (DPF) who had a history of asbestos exposure, but whose biopsies did not meet established criteria for asbestosis, and compare it with the fiber burden in confirmed asbestosis cases.
Fiber burden analysis was performed using scanning electron microscopy and energy-dispersive x-ray analysis of lung parenchyma from 86 patients with DPF and 163 patients with asbestosis. The correlation of the number of asbestos fibers found for a quantitative degree of fibrosis was analyzed.
The fibrosis scores of the asbestosis cases correlated best with the number of uncoated commercial amphibole fibers. Seven DPF cases fell within the 95% interval of asbestos body count by light microscopy and 3 cases within that of the total commercial amphibole fiber count.
Strict histologic criteria are useful for positive identification of asbestosis among cases of advanced pulmonary fibrosis. Few DPF patients with history of asbestos exposure whose biopsies did not meet the criteria for asbestosis may have asbestos fiber counts in the range seen in asbestosis, and fiber type identification by scanning electron microscopy with energy-dispersive x-ray analysis should be considered in these rare instances to avoid false-positive and false-negative diagnoses of asbestosis.
Mortality trends in the USA show that deaths from asbestosis are increasing, while deaths related to other pneumoconiosis are declining.
To analyse the association between asbestos consumption and asbestosis mortality trends.
In an epidemiological time series study, we used a modern computer-intensive local regression method to evaluate the relationship between asbestos consumption per capita (1900-2006) as the predictor variable and number of deaths from asbestosis (1968-2004). The predictor variable was progressively lagged by annual increments from 30 to 60 years and the goodness of fit assessed for each lag period. The model having the smallest Akaike's Information Criteria was used to derive extrapolated estimates of future mortality based on more recent asbestos consumption data.
Asbestos consumption per capita reached a peak in 1951 and gradually declined until 1973, when it started to drop rapidly. In 2006, it was 0.0075 kg/person/year. There were 25 564 deaths from asbestosis over the period 1968-2004. The best-fitting model (adjusted coefficient of determination (R(2)) = 99.7%) for 1968-2004 deaths from asbestosis used asbestos consumption per capita 48 years prior (1920-1956) and the log value of asbestos consumption per capita 43 years prior (1925-1961). This model predicts a total of 29 667 deaths (95% CI 19 629 to 39 705) to occur during 2005-2027 (an average of 1290 deaths per year).
This study demonstrates a clear association between asbestos consumption and deaths from asbestosis and indicates that asbestosis deaths are not expected to decrease sharply in the next 10-15 years.
As part of an overall assessment of immunological function, several aspects of humorial immunity and circulating lymphocyte subpopulations were evaluated in a group of twenty-six patients with radiographic evidence of parenchylmal asbestosis. Statistical comparisons were made between the patient group and a comparable group of forty-five controls. Both the percentages and absolute numbers of circulating T lymphocytes were significantly reduced in the patient group compared with controls. Significant elevations of salivary secretory IgA and of serum IgA, IgG, IgM and IgE were noted amongst the patients compared with the controls. Non-organ-specific autoantibodies and cold-reactive lymphocytotoxins were present in high frequency in the patients' sera. Neoplasms were detected in four of the patients. The possible significance of these findings is discussed.
Mixed pneumoconiosis is pulmonary disease due to two or more inhaled mineral irritants. Chronic disease due to beryllium has not been a component of any described mixed pneumoconiosis. A man with occupational exposure to a combination of dusts developed severe pulmonary disease. Silicosis, talcosis, asbestosis, and berylliosis were all documented by an open biopsy of the lung. The varieties of mixed pneumoconiosis are summarized.
Bronchoalveolar lavage is an invaluable means of accurately evaluating the inflammatory and immune processes of the human lung. Although lavage recovers only those cells and proteins present on the epithelial surface of the lower respiratory tract, comparison with open lung biopsies shows that these constituents are representative of the inflammatory and immune systems of the alveolar structures. With the use of these techniques, sufficient materials are obtained from normal individuals to allow characterization of not only the types of cells and proteins present but their functions as well. Such observations have been useful in defining the inflammatory and immune capabilities of the normal lung and provide a basis for the study of lung disease. Lavage methods have been used to characterize inflammatory and immune processes of the lower respiratory tract in destructive, infectious, neoplastic, and interstitial disorders. From the data already acquired, it is apparent that bronchoalveolar lavage will yield major insights into the pathogenesis, staging, and therapy decisions involved in these disorders. (Am J Pathol 97:149--206, 1979).
This paper describes the characteristic clinical features, mortality and survival rate of 202 patients diagnosed as having asbestosis by the Institute of Occupational Health between 1934 and 1976. One hundred and thirty-three patients were subjected to a clinical reexamination. Major findings included breathlessness in 118 (88.7%), persistent sputum in 95 (71.4%), crepitations in 77 (58.0%) and finger clubbing in 43 (32.3%). Of the 95 patients with persistent sputum, 19 (20.0%) were nonsmokers. Of the 174 men registered as having asbestosis, 56 had died, whereas the expected number of deaths among men of the same age in the Finnish general population was only 23.4. The respective figures for lung cancer were 19 observed and 2.1 expected. No excess mortality was found for other malignomas. Among men with asbestosis, the life expectancy was shorter for smokers than for non- and exsmokers.
The diagnosis of asbestos-associated pulmonary fibrosis was established in 3 patients by finding ferruginous bodies in transbronchial lung biopsies. Ferruginous bodies may be difficult to identify in histologic preparations when they are not oriented parallel to the plane of tissue section or when camouflaged by anthracotic pigment. We describe a simple method to enhance diagnostic sensitivity by digesting biopsy tissue and examining the filtered residue for ferruginous bodies.
A variety of cancers have been documented in patients exposed to asbestos dust. Since a deranged immune system may play a rôle in cancer development, the general level of immunocompetence was studied in a group of twenty-six patients with radiographically defined asbestosis, who might be at risk of developing asbestos-related neoplasms. Statistical comparisons were made with a comparable control group. A disproportionate number of the patients displayed cutaneous energy to certain recall antigens and to 2,4-dinitrochlorobenzene. In vitro studies of cellular immunity, as evaluated by phytohaemagglutinin-induced proliferative and cytotoxicity assays, showed significantly lower values amongst the patient group. Serum inhibitors of mitogen-induced lymphocyte transformation were also detected in several of the patients. The possible significance of these findings is discussed.
To investigate the influence of cigarette smoking on bronchoalveolar lavage (BAL) cellularity in asbestos-induced lung disease, we compared BAL cells in asbestos-exposed, nondiseased subjects (n = 20) with those with either asbestosis (n = 25) or asbestos-induced pleural fibrosis (n = 28). Patients with asbestosis (ILO greater than or equal to 1/0) had higher concentrations of BAL macrophages (p = 0.04), neutrophils (p = 0.003), and eosinophils (p = 0.01), while patients with asbestos-induced pleural fibrosis (circumscribed plaques and diffuse pleural thickening) had higher concentrations of BAL lymphocytes (p = 0.02). Within our study population, however, cigarette smoking (smoking status or pack-years of smoking) was strongly associated with BAL macrophages, neutrophils, and eosinophils but was not associated with the concentration of BAL lymphocytes. Using multivariate analysis, we found that although asbestosis remained associated with higher concentrations of BAL macrophages, neutrophils, and eosinophils, cigarette smoking had a far greater contribution to the concentrations of BAL macrophages and eosinophils than did asbestosis. Although cigarette smoking accounted for 17 to 18% of the variance of BAL macrophages and eosinophils, asbestosis was associated with approximately 6% of the variance associated with these cells. In contrast, the concentration of BAL neutrophils remained associated with asbestosis and was not influenced by smoking behavior. We conclude that cigarette smoking strongly influences BAL cellularity (macrophages and eosinophils) in our patients with asbestosis but does not appear to affect the type or concentration of BAL cells in patients with asbestos-induced pleural fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Radiographic evidence of interstitial fibrosis (IF) secondary to asbestos inhalation (using the International Labour Office [ILO] profusion of small irregular opacities) was compared with FVC as an independent indicator of IF. In addition, spirometric indices of airflow (FEV1/FVC and FET25-75%) were correlated with the radiographic profusion score. A study of 2,611 long-term insulators was well designed for these analyses since all subjects were from the same trade, there were sufficient (n = 515) nonsmokers to assess the effects of asbestos exposure in the absence of smoking, most (60%, n = 1,557) of the workers had parenchymal abnormalities (scores greater than or equal to 1/0), and there was a greater prevalence of high scores than in other published series (347 workers or 13.3% had scores greater than or equal to 2/1). Looking at all subjects, the FVC decreased as profusion score increased. The FVC was abnormal (88.0% of predicted) even when the profusion score was clearly normal (0/0). The FVC was lower at any score in smokers and in workers with pleural thickening (more so with diffuse thickening). There was, however, no difference in FVC between intermediate scores 0/1 versus 1/0 and 1/2 versus 2/1. Airflow increased with greater profusion, tending to overcome a decrease seen at lesser profusion scores. These results provide a greater understanding of the relationships among profusion scores, smoking, pleural diseases, and pulmonary function.
Diffuse interstitial lung disease in asbestos-exposed workers is presumed to represent asbestosis. Among 176 asbestos-exposed persons for whom lung tissue was available, we found nine with clinical features consistent with asbestosis, but histologic sections failed to demonstrate asbestos bodies, the usual requirement for pathologic diagnosis of asbestosis (Group I). These nine were compared by analytic electron microscopy with nine persons with idiopathic pulmonary fibrosis (Group II), and with nine persons with all the criteria of asbestosis (Group III). The three groups did not differ significantly with respect to lung burden of chrysotile or tremolite and actinolite, but Group III had a lung burden of amosite and crocidolite that was three orders of magnitude greater than in Groups I and II, with no overlap. We conclude that (1) the American Thoracic Society criterion of "a reliable history of exposure" is sometimes difficult to define; (2) asbestos bodies are seen in tissue sections only when exposure has been reasonably high, and given the proper clinical setting, the presence of diffuse fibrosis and asbestos bodies in tissue sections are sensitive and specific criteria for a diagnosis of asbestosis; and (3) the prevalence here of 5.1% nonasbestos-induced interstitial lung disease among asbestos-exposed persons is artefactually high because of atypical case selection. However, because asbestosis is a disappearing disease, such cases will become more frequent. The identification of these other diseases is important because therapy and prognosis may differ from that of asbestosis.
Although asbestos bodies are easily identified in bronchoalveolar lavage (BAL) fluid and are thought to be strongly associated with the asbestos body burden in the lung parenchyma, the clinical utility and reliability of this biologic measure of exposure has not been sufficiently studied. To assess the clinical relevance of BAL asbestos bodies we compared this bioassay of exposure to other measures of exposure and also indices of lung disease in asbestos-exposed workers (n = 71). The median concentration of asbestos bodies was 0.8 bodies per ml of BAL fluid (range 0 to 34.3). Seven workers or 9.9% had zero asbestos bodies identified in the BAL fluid. The concentration of BAL asbestos bodies was not associated with the duration of exposure (r = -0.02), the time from first exposure to asbestos (r = 0.12), or the time since last exposure to asbestos (r = 0.05). Moreover, radiographic and physiologic measures of asbestos-induced lung disease were not found to be associated with the concentration of BAL asbestos bodies. In fact, of the seven study subjects with zero BAL asbestos bodies, the mean duration of exposure was 32 yr, and six of these subjects had radiographic evidence of asbestos-induced lung disease. To assess the reliability of measuring BAL asbestos bodies, we performed a second bronchoscopy on 54 subjects and directly compared the concentration of BAL asbestos bodies from both the first and second BAL samples. Within these 54 subjects, the concentration of BAL asbestos bodies was found to be a very reliable measure (r = 0.76; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
The mineral fiber content of lung parenchyma in 24 cases of diffuse pulmonary fibrosis of unknown cause was determined by scanning electron microscopy and compared with that of 36 autopsy cases of histologically confirmed asbestosis and 20 autopsy cases of patients with normal lungs. Fibers were isolated from the lung using a hypochlorite digestion technique and collected on the surface of a polycarbonate filter. In addition, the types of fibers present (asbestos vs. other mineral fibers) were determined by energy dispersive x-ray analysis (EDXA). When the histologic grade of fibrosis in the cases of asbestosis was compared with the uncoated fiber content by means of linear regression analysis, it was determined that the fiber content of the 24 cases of diffuse pulmonary fibrosis of unknown cause was below the 95% confidence limit for asbestosis in every instance. Furthermore, the majority of fibers analyzed by EDXA were not asbestos in the cases with diffuse pulmonary fibrosis of unknown cause, whereas more than 90% of the fibers from the asbestosis cases were commercial amphiboles (amosite or crocidolite). It was concluded that most patients with advanced pulmonary fibrosis whose tissue samples do not meet histologic criteria for asbestosis do not have asbestos-induced fibrosis, even though there may be some history of exposure to asbestos. In such cases, scanning electron microscopic analysis of mineral fiber content and EDXA of the types of fibers present often provide useful information with regard to the correct classification of these cases.
Asbestos bodies (AB) have long been recognized in light microscopic (LM) sections of pulmonary hilar lymph nodes (LN) from patients with asbestos-related diseases, but the presence of AB on LM has not been correlated with the lung AB burden. The purpose of the present study was to determine whether AB in histologic sections of LN are indicative of heavy lung asbestos burdens. Twenty cases (17 with asbestosis, 15 with carcinoma of the lung, and two with malignant pleural mesothelioma) with at least one AB on a hilar LN section were identified. Bleach digestion of lung tissue in 15 cases demonstrated a median of 24,000 AB/g by LM and 44,000 AB/g by scanning electron microscopy. Digestion of hilar nodes demonstrated 21,800, 15,500, and 3,200 AB/g by LM in three cases which had lung burdens of 22,000, 481,000, and 5470 AB/g, respectively. A fourth LN specimen contained 322,000 AB/g in a case with no lung available to digest. Mean AB lengths in the LN in three cases were 48, 45, and 27 microns. Fourteen control cases of men over 50 without known asbestos exposure or asbestos-related disease had no AB in LN sections even after staining for iron. Among fourteen patients with parietal pleural plaques and an elevated lung asbestos body content, AB were observed in iron-stained LN sections in only two cases. These two patients had 3240 and 610 AB/g lung tissue, respectively (normal range 0 to 20 AB/g). We conclude that the finding of AB on a histologic section of hilar LN is generally indicative of a heavy lung AB burden.(ABSTRACT TRUNCATED AT 250 WORDS)
Considerable controversy surrounds the question of whether cigarette smoking has the potential to increase the prevalence of small opacities on chest roentgenographs among asbestos-exposed workers. To compare the relative contribution of smoking with other predictors of the presence of roentgenographic small opacities, we examined 661 men enrolled in a double-blind, randomized trial designed to assess the efficacy of vitamin A and beta-carotene in the prevention of lung cancer among workers with heavy occupational asbestos exposure. Subjects in the study population had a mean latency of 35 yr from first asbestos exposure and a mean of 28 yr in their trade. The prevalence of roentgenographic abnormalities consistent with asbestos exposure was 26% for pleural abnormalities alone, 10% for parenchymal abnormalities alone, and 20% for pleural and parenchymal abnormalities together. We investigated occupation, age, latency from first asbestos exposure, and smoking status as predictors of roentgenographic small opacities. Smoking history, independent of latency, contributed to the prevalence and extent of small opacities, but its effect was less than that of latency. We conclude, that in the setting of heavy occupational exposure to asbestos, cigarette smoking confers added risk for the development of roentgenographic small opacities.
We evaluated whether restrictive lung function among asbestos-exposed individuals with pleural fibrosis was caused by radiographically inapparent parenchymal inflammation and/or parenchymal fibrosis. All 24 study participants were sheet metal workers who were nonsmokers with normal parenchyma on posteroanterior chest radiograph. These subjects had either normal pleura (n = 7), circumscribed plaques (n = 9), or diffuse pleural thickening (n = 8). After controlling for age, years in the trade, and pack-years of smoking, we found that sheet metal workers with diffuse pleural thickening had a lower forced vital capacity (P less than 0.001), total lung capacity (P less than 0.01), and CO-diffusing capacity of the lung (P less than 0.05) than those with normal pleura. Similarly, sheet metal workers with circumscribed plaques were found to have a reduced forced vital capacity; however, because of the small number of study subjects, this difference (regression coefficient = -11.0) was only marginally significant (P = 0.06). Although circumscribed plaque and diffuse pleural thickening were both associated with a lymphocytic alveolitis and a higher prevalence of parenchymal fibrosis on high-resolution computerized tomography (HRCT) scan, neither a lymphocytic alveolitis nor the finding of parenchymal fibrosis on HRCT scan influenced the relationship between pleural fibrosis and restrictive lung function. We conclude that pleural fibrosis is associated with restrictive lung function and abnormally low diffusion that appears to be independent of our measures of parenchymal injury (chest X-ray, bronchoalveolar lavage, and HRCT scan).(ABSTRACT TRUNCATED AT 250 WORDS)
It has been suggested that because chrysotile asbestos forms asbestos bodies poorly, use of the traditional histologic requirements (diffuse interstitial fibrosis plus asbestos bodies) for the diagnosis of asbestosis, may lead to an underdiagnosis of this condition in workers exposed only to chrysotile. We examined lungs from 25 chrysotile miners with diffuse interstitial fibrosis. Asbestos bodies were found easily in histologic section using hematoxylin and eosin stains in all cases. Mineralogic analysis of four cases showed that 46 of 72 (64%) bodies isolated and examined contained chrysotile cores, and 21 of 72 (29%) bodies contained cores of the amphiboles tremolite and actinolite. By contrast, tremolite and actinolite constituted the majority of uncoated fibers in these cases. The mean length for bodies formed on chrysotile was 35 micron, and for bodies formed on tremolite or actinolite, 36 micron. We conclude that (1) the usual histologic criteria for the diagnosis of asbestos are applicable to chrysotile-exposed workers; (2) in workers with occupational chrysotile exposure, bodies form readily on this mineral; and (3) asbestos bodies in these lungs reflect the presence of long asbestos fibers.