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A case of giant cell interstitial pneumonia (GIF) that occurred in association with exposure to nitrofurantoin is presented. While the diagnosis of GIP is confirmed by histopathology, this diagnosis can be supported by the findings of bizarre multinucleated giant cells (MGC), elevated T lymphocytes, and a low T lymphocyte helper/suppressor ratio in the bronchoalveolar lavage fluid (BALF). Recognition of GIP as a rare manifestation of nitrofurantoin toxicity is important because prompt therapy may be associated with a favorable outcome.

Exposures to fibers and particles can be associated with several different lung injuries including bronchitis, bronchiolitis, pneumonitis, pleuritis, pulmonary alveolar proteinosis, pneumoconiosis, mesotheliomas, and lung cancers. The mechanism of biological effect exerted by fibers and particles has not been exactly defined. Exposures to all fibers and particles introduce a solid-liquid interface into the lower respiratory tract. These surfaces all have some concentration of oxygen-containing functional groups that demonstrate a capacity to coordinate iron. Radical generation is catalyzed by this metal resulting in a cascade of cell signaling, transcription factor activation, and mediator release. We propose that the ferruginous body (i.e., a fiber or particle with a coating of both protein and iron) provides direct evidence of a participation of iron in the biological effect of both fibers and particles. It is recommended that an identification of ferruginous bodies in the lung be regarded as support for a metal-catalyzed oxidative stress in the mechanism of cell and tissue injury.

Objectives: A large number of workers in the USA are exposed to chrysotile asbestos through brake repair, yet only a few cases of malignant mesothelioma (MM) have been described in this population. Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers. We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens., Methods: Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure. Lung fiber analyses were performed using scanning electron microscopy (SEM) in all cases for which formalin-fixed or paraffin-embedded lung tissue was available., Results: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose in the pleura and one in the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our upper limit of normal (range 0-20 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos fiber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysotile and non-commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers., Conclusions: Brake dust contains exceedingly low levels of respirable chrysotile, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM.

Background: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases., Methods: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos., Results: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background., Conclusions: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.

Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.