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Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 μm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers., Objective: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 μm in length, with particular attention to publications indicating that such fibers might be hazardous., Data Sources: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic., Conclusions: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 μm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 μm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.

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.

Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxidative stress. We describe 2 patients with ILD associated with exposure to synthetic textile fibers who demonstrated carbon-based ferruginous bodies suggesting an in vivo accumulation of iron by synthetic fibers after deposition in the lung. These iron-laden bodies varied from perfectly linear fibers to almost particulate matter. Linear structures were irregularly interrupted by deposition of iron-abundant material. The capacity of these synthetic fibers to complex iron and generate an oxidative stress is confirmed in vitro.

Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m3) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (> or = 8 microm) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model.

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.

We studied the asbestos body (AB) content of bronchoalveolar lavage fluid from 20 patients with a history of occupational asbestos exposure, 31 patients with sarcoidosis and 5 patients with idiopathic pulmonary fibrosis. The cellular lavage pellet was digested in sodium hypochlorite and filtered onto Nuclepore filters for AB quantification by light microscopy. ABs were found in 15 of 20 asbestos-exposed individuals, 9 of 31 sarcoidosis cases and 2 of 5 patients with idiopathic pulmonary fibrosis. There was a statistically significant difference in the number of ABs per million cells recovered or per milliliter of recovered lavage fluid in the asbestos-exposed group as compared to the other categories of chronic interstitial lung disease. The highest levels occurred in patients with asbestosis. Large numbers of asbestos bodies in the lavage fluid (greater than 1 AB/10(6) cells) were indicative of considerable occupational asbestos exposure, whereas occasional bodies were a nonspecific finding.

A 61-yr-old woman was evaluated for dyspnea on exertion and interstitial lung disease. A unique association between inhaled particulates from wood burning and interstitial pneumonitis was demonstrated. Bronchoalveolar lavage revealed numerous particulates and fibers, as well as cellular and immunoglobulin abnormalities. The particles were shown to be carbonaceous by energy dispersive X-ray analysis (EDXA). Inflammation and fibrosis were found surrounding them on open biopsy. The particle source was traced to a malfunctioning wood-burning heater in the patient's home. We present this case to highlight the usefulness of BAL and EDXA in the elucidation of particle-associated lung disease.

The Tyler Asbestos Workers Program is a continuing study of 1,105 former amosite asbestos workers. This report includes a study of six former workers, five of whom died and had autopsies, and one who underwent a lobectomy. Five of these men were exposed to asbestos for three months or less. Four had lung cancer, and one a rectal carcinoma. All were cigarette smokers. Ferruginous (asbestos) body content of the upper and lower lobes of the lungs was quantitated by a digestion technic. Tissue sections from upper and lower lobes were independently quantitated for fibrosis and ferruginous bodies, and chest roentgenograms were examined for interstitial fibrosis. (Control lung tissue was obtained from consecutive autopsies of 52 adults who did not have a known occupational exposure to asbestos.) Relatively low ferruginous body counts (less than 700/g lung tissue) were associated with mild degrees of fibrosis, and higher counts (greater than 10,000/g) with moderate to severe fibrosis. Mild to moderate pulmonary fibrosis could be identified on tissue sections before interstitial changes were detectable by chest roentgenograms.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by branching bony spicules found in association with pulmonary fibrosis. The authors report two cases, the first of which occurred in a patient with acute myeloblastic leukemia and was associated with the unique finding of leukemic involvement of marrow spaces in the metaplastic bone. The second case showed DPO in combination with asbestosis, a heretofore unreported association.

A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removal of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.

Andrew J Ghio,1 Elizabeth N Pavlisko,2 Victor L Roggli,2 Nevins W Todd,3 Rahul G Sangani4 1Human Studies Facility, US Environmental Protection Agency, Chapel Hill, NC, 27514, USA; 2Department of Pathology, Duke University, Durham, NC, USA; 3Department of Medicine, University of Maryland, Baltimore, MD, 21201, USA; 4Department of Medicine, West Virginia University, Morgantown, WV, USACorrespondence: Andrew J GhioHuman Studies Facility, US Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC, USAEmail ghio.andy@epa.govAbstract: It is proposed that the mechanistic basis for non-neoplastic lung injury with cigarette smoking is a disruption of iron homeostasis in cells after exposure to cigarette smoke particle (CSP). Following the complexation and sequestration of intracellular iron by CSP, the host response (eg, inflammation, mucus production, and fibrosis) attempts to reverse a functional metal deficiency. Clinical manifestations of this response can present as respiratory bronchiolitis, desquamative interstitial pneumonitis, pulmonary Langerhans’ cell histiocytosis, asthma, pulmonary hypertension, chronic bronchitis, and pulmonary fibrosis. If the response is unsuccessful, the functional deficiency of iron progresses to irreversible cell death evident in emphysema and bronchiectasis. The subsequent clinical and pathological presentation is a continuum of lung injuries, which overlap and coexist with one another. Designating these non-neoplastic lung injuries after smoking as distinct disease processes fails to recognize shared relationships to each other and ultimately to CSP, as well as the common mechanistic pathway (ie, disruption of iron homeostasis).Keywords: iron, ferritins, pulmonary disease, chronic obstructive, pulmonary emphysema, chronic bronchitis, hypertension, pulmonary, pulmonary fibrosis