Asbestos-exposed Individuals Research Articles

High-Resolution Computed Tomography in Cases with Environmental Exposure to Asbestos in Turkey

Background and Objectives: Although all parts of the lung can be affected as a consequence of asbestos exposure, most CT protocols tend to scan only the middle and lower parts of the thorax. The aim of this study was to investigate parenchymal and pleural lesions of persons exposed to environmental asbestos, using a high-resolution computed tomography (HRCT) protocol scanning the whole thorax. Methods: We analyzed the chest radiographs and HRCT scans of 26 patients who presented bilaterally with multiple pleural plaques related to environmental asbestos exposure. Results: Twenty-four cases (92%) had an abnormal HRCT suggestive of asbestosis. Apart from common HRCT changes related to asbestosis, we detected apical pleural thickening (APT) in 9 cases as well as a coarse honeycomb pattern adjacent to APT in 7 of these cases. Cavitary lesions due to pulmonary tuberculosis were observed on HRCT scans from 4 patients in total. Neither apical pulmonary fibrosis nor cavitary lesions were visible on chest radiographs. Conclusions: We suggest that the HRCT protocol for examining asbestos-exposed individuals with pleural plaques on chest X-rays should include the whole thorax, since the asbestos-related pathologies may involve all parts of the lung.

Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals.

Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals.

Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET).

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Analyzing the genes and peptide growth factors expressed in lung cells in vivo consequent to asbestos exposure and in vitro.

Inhalation of fibrogenic particles causes injury to the bronchiolar-alveolar epithelium. Consequently, there is a rapid proliferative response as the epithelium recovers and interstitial mesenchymal cells divide and produce connective tissue. In our model of brief (5-hr) exposure to chrysotile asbestos (approximately 1000 fibers/cc) in rats and mice, these events result in focal scarring at the bronchiolar-alveolar duct junctions in a histopathologic pattern identical to that seen in asbestos-exposed individuals. After 3 consecutive days of exposure, these lesions persist for at least 6 months postexposure. We postulate that cell proliferation and production of extracellular matrix is mediated in large part by three peptide growth factors, transforming growth factors alpha and beta (TGF-alpha and -beta), and platelet-derived growth factor (PDGF) A- and B-chains. To test this hypothesis in part, we have asked whether the genes that code for these growth factor proteins are activated at sites of asbestos-induced lung injury. If these genes were not activated, it would be reasonable to suspect that other potent growth factors and cytokines released during lung injury could be the primary mediators of fibroproliferative lung disease. In the studies reported here, we show, by in situ hybridization (ISH) and immunohistochemistry, that the four genes and their concomitant proteins are expressed within 24 hr in the bronchiolar-alveolar epithelium and underlying mesenchymal cells. RNase protection assay and ISH showed that the PDGF gene was upregulated during the first 5 hr of exposure and all the gene products remained above control levels for at least 2 weeks postexposure. TGF-alpha is a potent mitogen for epithelial cells, whereas the PDGF isoforms are potent growth factors for mesenchymal cells. TGF-beta retards fibroblast growth but stimulates extracellular matrix synthesis. Further studies using gene knockouts, appropriate antibodies, or antisense technology will be necessary to prove whether any of the growth factors are playing a significant role in fibrogenic lung disease. In addition, we have carried out a series of studies using type II alveolar epithelial cells purified from adult mouse lungs and maintained for up to 8 weeks in serum-free culture. These cells exhibit high transepithelial resistance values and they release TGF-beta 1 and -beta 2. This cell type also has been cultured from TGF-alpha knockout mice, resulting in monolayers with increased transepithelial resistance. This combination of studies in vivo and in vitro will allow us to pursue the mechanisms through which growth factors mediate lung fibrosis.

Causes of pulmonary impairment in asbestos-exposed individuals with diffuse pleural thickening.

To examine whether diffuse pleural thickening (DPT) causes impairment of pulmonary function independent of other manifestations of asbestos-related disease, we studied individuals selected from 1,150 men with occupational asbestos exposure who had undergone pulmonary function testing and computed tomographic (CT) scanning. The CT scans revealed 84 subjects with DPT as defined for CT. Of these 84 subjects, 53 eligible study cases were matched by age with a referent group without DPT from the same exposed group. No difference was demonstrated between cases and referents in smoking history, length of exposure, latency, or the proportion with either interstitial fibrosis or pleural plaques. Individuals with DPT demonstrated significantly reduced forced vital capacity (FVC) (p = 0.002) and diffusing capacity for carbon monoxide (DLCO) (p = 0.002) as compared with the referents. No difference was found in the two groups' FEV1 to FVC ratio (FEV1/FVC). Individuals with DPT and either interstitial fibrosis or pleural plaques showed a significantly lower FVC than did those with fibrosis or pleural plaques alone. Individuals with DPT and rounded atelectasis had similar pulmonary function to those with DPT and no rounded atelectasis. Subjects with DPT had a more frequent history of coronary bypass surgery than referents (19% versus 2%; p = 0.008). We conclude that subjects with DPT have restrictive pulmonary function and reduced diffusing capacity independent of other manifestations of asbestos-related disease.

Differentiation of the ILO Boundary Chest Roentgenograph (0/1 to 1/0) in Asbestosis by High-Resolution Computed Tomography Scan, Alveolitis, and Respiratory Impairment

High-resolution computed tomography (HRCT) scans have been advocated as providing greater sensitivity in detecting parenchymal opacities in asbestos-exposed individuals, especially in the presence of pleural fibrosis, and having excellent inter- and intraobserver reader interpretation. We compared the 1980 International Labor Organization (ILO) International Classification of the Radiographs of the Pneumoconioses for asbestosis with the high-resolution CT scan using a grid scoring system to better differentiate normal versus abnormal in the ILO boundary 0/1 to 1/0 chest roentgenograph. We studied 37 asbestos-exposed individuals using the ILO classification, HRCT grid scores, respiratory symptom questionnaires, pulmonary function tests, and bronchoalveolar lavage. We used Pearson correlation coefficients to evaluate the linear relationship between outcome variables and each roentgenographic method. The normal HRCT scan proved to be an excellent predictor of "normality," with pulmonary function values close to 100% for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO) and no increase in BAL inflammatory cells. Concordant HRCT/ILO abnormalities were associated with reduced FEV1/FVC ratio, reduced diffusing capacity, and alveolitis consistent with a definition of asbestosis. In our study, the ILO classification and HRCT grid scores were both excellent modalities for the assessment of asbestosis and its association with impaired physiology and alveolitis, with their combined use providing statistical associations with alveolitis and reduced diffusing capacity.

Elevated interleukin-8 in the alveolitis of individuals with asbestos exposure.

Asbestosis is a fibrotic and inflammatory interstitial lung disease occurring after chronic occupational exposure to asbestos. An alveolitis has been described with activated alveolar macrophages and increased neutrophils as sampled by bronchoalveolar lavage (BAL). Animal models and in vitro studies demonstrate that asbestos can stimulate alveolar macrophages to release neutrophil chemotactic factor. We performed BAL on 18 nonsmoking individuals with asbestos exposure and observed a twofold increase in percent neutrophils recovered. Alveolar macrophages cultured in vitro from the asbestos-exposed individuals spontaneously released significant amounts of the neutrophil chemotaxin, interleukin-8 (IL-8). In addition, the alveolar macrophages expressed a 2.7-fold increase in steady state mRNA levels compared to unexposed normal controls utilizing the reverse transcriptase/polymerase chain reaction. In vitro experiments confirmed that crocidolite or chrysotile asbestos could stimulate the release of IL-8 from mononuclear phagocytes in a dose-dependent fashion. We conclude that asbestos exposure causes a mild neutrophilic alveolitis, and that IL-8 is one potential mediator capable of contributing to this inflammation in the lower respiratory tract.

Distribution of Asbestos Bodies in the Human Lung as Determined by Bronchoalveolar Lavage

Asbestos-related lung diseases tend to have distinct local distributions, for example, asbestosis first appears and tends to be more severe in the peripheral parts of the lower lung zones. The risk for asbestosis is related to the total asbestos burden of the lung. This suggests that the lower lobes in asbestos-exposed individuals may contain more asbestos than the other lobes. To test whether such topographic differences exist, we compared the number of retrieved asbestos bodies (AB) per ml BAL fluid in three groups of occupationally asbestos-exposed subjects who underwent BAL at different sampling sites. In Group 1 (n = 24) we performed BAL at three sites, namely in a segment of the right upper, right middle, and right lower lobe, to evaluate differences in asbestos body burden from lung apex to basis. There was a distinct increase in BAL asbestos body concentrations from the upper (21.2 +/- 9.1 AB/ml BAL fluid) to the middle (30.4 +/- 12.8 AB/ml BAL fluid) and to the lower lobe (56.0 +/- 20.2 AB/ml BAL fluid), all differences being significant (p < 0.01). In Group 2 (n = 40), we found good interlobar correlations for asbestos body counts between the right middle lobe (21.0 +/- 5.8 AB/ml BAL fluid) and the lingula (22.4 +/- 5.9 AB/ml BAL fluid) (r = 0.941, p < 0.001) and, in Group 3 (n = 15), between the ventral basal segment of the right (41.2 +/- 13.6 AB/ml BAL fluid) and left lung (39.0 +/- 13.6 AB/ml BAL fluid) (r = 0.966, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A diagnostic approach to asbestosis, utilizing clinical criteria, high resolution computed tomography, and gallium scanning.

Seventy-five individuals known to have significant exposure to asbestos were evaluated by physical exam, pulmonary function tests (PFT), chest radiographs, high resolution computed tomography (HRCT), gallium-67 scanning, and various laboratory exams. Sixteen subjects met three of the following four criteria and were considered to have clinical asbestosis: 1) bibasilar rales, 2) FVC < 80% of predicted, 3) DLCO < 80% of predicted, and 4) an abnormal chest radiograph. Evaluations which included HRCT and Ga scanning detected pulmonary disease in these asbestos-exposed individuals in many cases where other modalities were unable to demonstrate significant abnormalities. While only 21% of the subjects satisfied commonly accepted criteria for the diagnosis of asbestosis, 75% had evidence of disease by both HRCT and gallium scanning. These data suggest that it may be time to include HRCT and Ga scanning when evaluating asbestos-exposed individuals, especially in cases where evaluations by physical exam, PFTs, and chest radiographs are non-diagnostic.

Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure.

The lung macrophage is proposed to be involved in the development of asbestos-induced pulmonary fibrosis. Knowledge of the effects of long-term asbestos exposure on lung macrophage cytokine release should better define the role of the macrophage in fibrogenesis. This study examines the effects of acute in vitro asbestos exposure and chronic in vivo asbestos exposure on human alveolar macrophage cytokine release. As indicators of asbestos-induced macrophage activation, the cellular release of IL-1 beta, TNF-alpha, IL-6, GM-CSF, and PGE2 was measured during a 24-h in vitro culture. Alveolar macrophages from normal volunteers were cultured in vitro with chrysotile asbestos. Of the factors measured, only TNF-alpha was elevated in response to asbestos exposure. Alveolar macrophages from asbestos-exposed individuals were placed into one of two groups based on their exposure history. These two groups were matched for age, smoking history, and diagnosis; none met the criteria for asbestosis. Cells isolated from subjects that had been exposed to asbestos for more than 10 years secreted enhanced basal amounts of IL-1 beta, TNF-alpha, IL-6, and PGE2, while those who had been exposed for less than 10 years did not. The results indicate that while asbestos had minimal acute effects on cytokine production by the human alveolar macrophage, intense, chronic exposure to asbestos leads to the enhanced basal release of significant amounts of several cytokines that have activity for the fibroblast, even in the absence of overt fibrosis.

Asbestos-related chest diseases: Plain radiographic findings

In summary, there are a wide range of pulmonary manifestations seen in asbestos-exposed individuals from pleural and parenchymal fibrosis to pleural and parenchymal malignancy. The chest roentgenogram has assumed an important role in the detection and surveillance of asbestos-related pleural and parenchymal changes.

Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro.

Tumor necrosis factor (TNF) is a cytokine released predominantly by monocytes/macrophages that has been shown to modulate a variety of different immune and metabolic functions. To understand the regulatory mechanisms of TNF in governing responses in the pleural cavity following deposition of fibrous dust in the airspace of the lung, we studied the capability of leukocytes, lavaged from the pleural cavity, to release TNF in culture. TNF production by lavaged pleural leukocytes was measured using the L-929 TNF-sensitive cell line, after intratracheal instillation of crocidolite asbestos. A high level of TNF activity was found in the supernatants of normal, unstimulated pleural leukocytes; the addition of 100 ng/ml lipopolysaccharide to the culture increased the activity up to threefold. Following intratracheal instillation of 5 mg crocidolite asbestos, the pleural leukocytes secreted less TNF than the control. With increasing mass of intratracheally instilled asbestos, there was a dose-dependent reduction in TNF release. Changes in the population of the pleural leukocytes or their number could not be related to variation in TNF activity. These results suggest that exposure of rat lungs to crocidolite asbestos by intratracheal instillation affects the response of pleural leukocytes without causing changes in the population. Such changes in the bronchoalveolar space may be related to the pleural pathology found in asbestos-exposed individuals.

Asbestosis: Diagnostic Dilution

The term "asbestosis" usually has been applied to a disease characterized by diffuse pulmonary interstitial fibrosis. It was often associated with a significant adverse impact on the individual. A review of case definitions employed in published research studies show stability of the criteria for asbestosis case definitions over the past decade. Nevertheless, additional modalities have been suggested for the early diagnosis of asbestosis. It is probable that the significance of such abnormalities may be different from that of usual asbestosis, and there is therefore a need to carefully define the manner in which the terms are used. Additional anomalies may be seen in asbestos-exposed individuals including small airway physiologic abnormality, pathologic evidence of inflammation near the airways, positive gallium scan, abnormal lung compliance, exercise test abnormalities, CAT scan findings, and high-resolution CAT scan findings.

High-resolution computed tomography of asbestos-related diseases

There is growing evidence that HRCT can detect both interstitial and pleural disease in advance of conventional clinical or radiographic studies. Limited HRCT scans are roughly competitive in time and cost with 4-view radiographic examinations. The use of limited HRCT for large-scale screening of asbestos-exposed individuals is controversial. Hopefully this will be resolved as we gain greater understanding of the specificity of HRCT and establish guidelines for standardizing technique and interpretation. At present, limited HRCT scans can supplement the chest radiographic evaluation of subjects in whom there is equivocal parenchymal or pleural disease, unexplained abnormalities on pulmonary function tests, or significant coexisting pleural disease that precludes evaluation of the underlying parenchyma. Interstitial abnormalities on HRCT may be reasonably ascribed to asbestos exposure when there is clear historical documentation of significant, remote dust exposure or concomitant evidence of typical bilateral asbestos-related pleural disease. A subpleural distribution of interstitial abnormality in nondependent lung is important to establish the diagnosis of interstitial fibrosis. Although both unilateral pleural and parenchymal fibroses have been reported, lesions should generally be present bilaterally. In individuals with combined asbestos-cigarette smoke exposure in whom symptoms or functional abnormalities are present, HRCT may play a central role in distinguishing emphysematous lung destruction from the peripheral interstitial changes of asbestosis. Finally, in individuals with significant pleural or parenchymal fibrosis, focal lung masses may not be visible on chest radiographs. In these individuals, CT protocols that sample all regions of the thorax are appropriate.

Computed Tomography of Asbestos-Related Pulmonary Parenchymal and Pleural Diseases

Computed tomography has acquired an increasingly central role in the evaluation of asbestos-exposed individuals. The advantages of increased contrast resolution and axial image display have extended our ability to interrogate areas of the pulmonary parenchyma and pleura that are inadequately seen on chest radiographs. The additional information to be gained from CT evaluation must be balanced by the additional expense and time required, particularly in view of the large numbers of asbestos-exposed individuals who will undergo screening over the coming decades. Ideally, imaging strategies that include CT should emphasize those problematic situations in which additional information will serve a differential or diagnostic function, alter the management or habits of the individuals, modify the working environment, or improve our understanding of asbestos-induced diseases. The chest radiograph is the mainstay in the imaging evaluation of asbestos-exposed individuals, providing an inexpensive and rapid appraisal of the presence of both focal and diffuse abnormalities of the pleura and lung parenchyma. Conventional (whole-thorax) CT may be an important adjunct in the following situations: (1) to clarify the presence of pleural thickening, particularly in distinguishing pleural disease from normal extrapleural soft tissues; (2) to stage and determine tumor extent in malignant pleural mesothelioma; (3) to identify optimal sites for biopsy of suspicious pleural changes; and (4) to detect and characterize lung cancers or other focal masses that may be obscured by extensive pleural or parenchymal fibrosis. Limited HRCT studies are roughly competitive in time and cost with four-view radiographic examinations. There is growing evidence that HRCT can detect interstitial disease in advance of conventional clinical or radiographic studies. However, the application of limited HRCT for large-scale screening is controversial. This issue will be resolved as we gain greater understanding of the specificity of HRCT and establish guidelines for standardizing the technique and image interpretation. At present, limited HRCT scans can supplement the evaluation of subjects in whom there is equivocal parenchymal or pleural disease on radiographs or unexplained abnormalities on pulmonary function tests. In individuals with significant pleural disease, HRCT can effectively define the presence and extent of interstitial fibrosis. In individuals with combined cigarette smoking-asbestos exposure in whom symptoms or functional abnormalities are present, HRCT may play a central role in distinguishing emphysematous lung destruction from the peripheral interstitial changes of asbestosis.

Radiographic abnormalities in asbestos insulators: Effects of duration from onset of exposure and smoking. Relationships of dyspnea with parenchymal and pleural fibrosis

Chest radiographs and spirometry were evaluated in 2,907 active and retired asbestos insulators; most (86.8%) had greater than or equal to 30 years from onset of asbestos exposure. Testing was performed in 19 cities in the United States during 1981-1983. Complete demographic, smoking, clinical, and radiologic data were obtained for 2,790 workers. This is the largest single group of insulators that has been studied. Five hundred forty-eight (19.7%) had never smoked cigarettes, 942 (33.9%) were current cigarette smokers, and 1,300 (46.6%) were ex-smokers. Only 439 (15.7%) workers had no radiographic evidence of asbestos-related disease (normal chest X-ray); 668 (23.9%) had pleural fibrosis only, 325 (11.6%) had parenchymal fibrosis alone, and 1,358 (48.7%) had both parenchymal and pleural fibrosis. The prevalence of radiographic parenchymal changes increased significantly (p less than .001) from 38.6% (DURONSET less than 30 years) to 70% (greater than or equal to 40 years). For pleural changes the comparative prevalences were 55% and 82%. Those with no history of cigarette smoking were more likely to have normal films than those with a history of smoking (19.2% versus 14.4% for current smokers and 15.2% among ex-smokers), and were less likely to have parenchymal fibrosis (44.5% versus 69.7% for current smokers and 60.2% of ex-smokers). Dyspnea, MRC grade 3 and higher, was more prevalent when pleural fibrosis was associated with interstitial pulmonary fibrosis (at all profusion levels of small opacities) than when pleural fibrosis was absent. Logistic regression analysis of factors contributing to such dyspnea showed that the presence of combined parenchymal and pleural abnormalities was a significant explanatory variable, in addition to age, smoking, and body mass (Quetelet index); the presence of parenchymal changes only or of pleural changes only, as factors contributing to dyspnea, did not reach the level of statistical significance in the regression analysis. The results of these examinations show that pleural fibrosis is a frequent finding in asbestos-exposed groups with long-term follow-up and that its functional significance is not negligible. The contribution of cigarette smoking to prevalence and severity of interstitial fibrosis is an additional reason for smoking cessation among asbestos-exposed individuals.

Determinants of restrictive lung function in asbestos-induced pleural fibrosis

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)

Asbestos-Induced Release of a Human Alveolar Macrophage-Derived Neutrophil Chemotactic Factor

Neutrophils accumulate in the alveoli of asbestos-exposed individuals. In determining whether asbestos fibers induce the release of neutrophil chemotactic factor (NCF) from human alveolar macrophages, alveolar macrophages (10(6) cell/mL) obtained by bronchoalveolar lavage from six non-asbestos-exposed control subjects were exposed to crocidolite (0.1 and 1 mg/mL), chrysotile (1 mg/mL), or medium alone for 4 h, and NCF activity was measured in the supernatants in a 48-well microchemotaxis chamber with polycarbonate membrane filters (pore size, 3 microns) and purified human neutrophils. Alveolar macrophages in medium alone released negligible amounts of NCF (4 +/- 1 neutrophils per high-power field [N/HPF]). When macrophages were exposed to crocidolite (0.1 and 1 mg/mL), significant NCF release occurred (43 +/- 9 and 105 +/- 32 N/HPF, respectively; p less than 0.01 for each amount compare to alveolar macrophages cultured in medium alone). Chrysotile (1 mg/mL) induced similar NCF release (96 +/- 14 N/HPF; p less than 0.01 compared to unstimulated alveolar macrophages). Partial characterization of the NCF by Sephadex G-25 fine gel filtration demonstrated a molecular size of less than 1,000 daltons. These results show that human alveolar macrophages release NCF after exposure to asbestos. Release of NCF by alveolar macrophages in asbestos-exposed individuals may play a central role in the pathogenesis of asbestosis.

Indomethacin augments lymphokine-activated killer cell generation by patients with malignant mesothelioma

Human malignant mesothelioma (MM) cells are resistant to natural killer (NK) cell lysis but susceptible to lysis by lymphokine-activated killer (LAK) cells from control individuals. The present study was performed to determine the capacity of patients with MM ( n = 22) and individuals occupationally exposed to asbestos (the major population at risk of developing this disease, n = 52) to generate LAK cells capable of effectively lysing human mesothelioma cells. Compared to controls ( n = 20), both patient groups demonstrated significantly depressed LAK cell activity against mesothelioma tumor cell targets (55 ± 3% lysis by controls vs 34 ± 3% lysis by patients with MM, P < 0.005; and 45 ± 3% lysis by asbestos-exposed individuals, P < 0.025). Addition of 10 μg/ml indomethacin during LAK cell generation restored normal LAK cell activity for patients with MM (52 ± 6% lysis of cultured human MM cells, P = NS compared to controls), suggesting that the defective cytolytic cell function observed in some patients with MM is a result of prostaglandin-induced immunosuppression. The ability of indomethacin to restore suppressed LAK cell activity in patients with MM suggests that the concomitant use of this agent in ex vivo LAK cell generation and in patients undergoing interleukin/LAK cell therapy may be beneficial.

Gallium Lung Scanning and Bronchoalveolar Lavage in Crocidolite-Exposed Workers

Gallium lung scanning is widely used to evaluate pulmonary inflammation in patients with interstitial lung disease but has not previously been reported in crocidolite-exposed workers. In order to characterize the pulmonary inflammation caused by crocidolite inhalation, GLS and BAL findings were related to chest x-ray film changes graded according to the ILO classification of roentgenograms of pneumoconioses. In individuals with roentgenographic evidence of asbestosis (CXR greater than or equal to 1/0, n = 15), 13 had a positive GLS and 13 had an abnormal BAL. In asbestos-exposed individuals with equivocal chest x-ray film changes (CXR 0/1, n = 12), six had a positive GLS and six had BAL changes (both GLS and BAL abnormal in three). In individuals with a normal chest x-ray film (CXR 0/0 n = 8), two had a positive GLS and two BAL changes (both abnormal in 1). These data demonstrate that most subjects with crocidolite-induced asbestosis have an abnormal GLS and BAL. In addition, many individuals with asbestos exposure and equivocal or no chest x-ray film changes have an abnormal GLS and/or BAL, suggesting the presence of active subclinical pulmonary inflammation in these individuals.