nitrogen-dioxide and Pulmonary-Fibrosis

This article discusses the nomenclature of respiratory disease, acute respiratory distress syndromes, hypersensitivity diseases, chronic respiratory disease, and the differential diagnosis of respiratory disease.

Topics: Alveolitis, Extrinsic Allergic; Anaphylaxis; Animals; Brassica; Cattle; Cattle Diseases; Chronic Disease; Diagnosis, Differential; Granuloma; Lung Neoplasms; Manure; Monoterpenes; Nitrogen Dioxide; Plant Poisoning; Pneumonia; Pneumonia, Atypical Interstitial, of Cattle; Pulmonary Fibrosis; Respiratory Distress Syndrome; Respiratory Tract Diseases; Smog; Terpenes; Zinc Oxide

Topics: Adult; Bronchi; Coal Mining; Environmental Exposure; Humans; Lung; Lung Neoplasms; Middle Aged; Nitrogen Dioxide; Ozone; Pneumoconiosis; Pulmonary Circulation; Pulmonary Emphysema; Pulmonary Fibrosis; Respiration; Rheumatoid Factor; Smoke; Spirometry; Sulfur Dioxide

Topics: Accidents, Occupational; Acute Disease; Humans; Japan; Male; Middle Aged; Nitrogen Dioxide; Poisoning; Pulmonary Fibrosis

Tumor necrosis factor a (TNFalpha) and manganese superoxide dismutase (MnSOD) are thought to play critical roles in the process of lung injury, repair, and disease. The induction of TNFalpha and MnSOD were examined in a model of progressive pulmonary fibrosis along the length of the alveolar duct in rats exposed for 1, 5, and 8 weeks to a combination of 0.8 ppm ozone and 14.4 ppm nitrogen dioxide. This oxidant injury model results in a triphasic response with an initial inflammatory stage during weeks 1-3, followed by a partial resolution at weeks 4-5, and a final stage of rapidly progressive fibrosis during weeks 6-8. Changes in TNFalpha and MnSOD labeling for the proximal and distal alveolar ducts of the lungs were quantified using immunohistochemistry and morphometric techniques at 1, 5, and 8 weeks of exposure. A significant elevation in MnSOD was noted in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following 8 weeks of exposure. Labeling for TNFalpha only in the proximal region of the alveolar duct, was significantly increased in alveolar macrophages after 1 and 8 weeks of exposure, while a significant increase in TNFalpha labeling of interstitial cells in proximal regions was noted at all time points. We conclude that MnSOD is elevated in areas of focal injury as well as the more distal protected areas of the lungs, while TNFalpha correlates strongly with both the temporal and spatial aspects of greatest cellular injury in the lungs.

Topics: Administration, Inhalation; Animals; Cell Count; Disease Models, Animal; Epithelial Cells; Humans; Immunoenzyme Techniques; Lung; Macrophages, Alveolar; Male; Nitrogen Dioxide; Ozone; Pulmonary Alveoli; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Time Factors; Tumor Necrosis Factor-alpha

To evaluate the early molecular events of oxidant-induced pulmonary fibrosis, rats were continuously exposed to 0.4 ppm ozone and 7 ppm nitrogen dioxide. The early responses to the combined gases could be divided into three phases. Acute pulmonary inflammation indicated by an increase in pulmonary edema as well as an influx of neutrophils into the airspaces first occurred on days 1 to 3 of the exposure. The pulmonary inflammation was reversed by day 8, and no biochemical or morphologic aspects of tissue responses were detected from days 15 to 45, suggesting that rats adapted to the stimuli during that period. Pulmonary fibrosis could be detected by an increase in the biomarker of lung collagen content at day 60 and by histopathologic evaluation by day 90. Enhanced expression of macrophage inflammatory protein-2 was observed only at day 1, whereas the pulmonary expression of transforming growth factor-beta was upregulated on days 60 and 90 of the exposure. Macrophage expressions of interleukin-1beta and interleukin-6 were enhanced during acute pulmonary inflammation; however, macrophage expression of tumor necrosis factor-alpha was elevated at both day 1 and days 60-90. Activation of nuclear factor-kappa B and increased expression of thioredoxin in the lungs was also observed at day 1 and days 60-90. The expression of antioxidant enzymes, such as manganeous superoxide dismutase and glutathione peroxidase, was not altered during exposure. These results indicate that macrophage activation and the expression of macrophage-derived cytokines may play an important role in the early pulmonary responses against the combined gases.

Topics: Administration, Inhalation; Albumins; Animals; Blotting, Northern; Body Weight; Bronchoalveolar Lavage Fluid; Collagen; Cytokines; DNA Primers; Glutathione Peroxidase; Hydroxyproline; Immunoenzyme Techniques; Interleukins; Lung; Male; Nitrogen Dioxide; Oxidants, Photochemical; Ozone; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase

Nitrogen dioxide (NO2), the oxidation product of nitric oxide (NO), is a reactive free radical forming gas, the inhalation of which has been reported to induce severe damage to distal airways. In order to quantify dose and time course of parenchymal and vascular damage, rats were exposed to 5, 10 and 20 ppm NO2 for 3 and 25 days, followed by quantitative histology and morphometry of the lung. Histological investigations of the short-term exposed animals showed structural alterations extending from slight interstitial oedema after exposure to 5 ppm, to epithelial necrosis and interstitial inflammatory infiltration after exposure to 10 ppm, and an additional intra-alveolar oedema after 20 ppm. The pulmonary arteries disclosed no qualitative changes, such as muscularization of intra-acinar vessels. Long-term exposure to 10 ppm and 20 ppm NO2 resulted in emphysema and slight centrilobular interstitial fibrosis. Morphometric analysis revealed the alveolar surface density to be significantly diminished after short-term exposure to 20 ppm NO2 and long-term exposure to 10 and 20 ppm NO2. The medial thickness of pulmonary arteries was significantly increased after short- and long-term exposure to 20 ppm NO2 and long-term exposure to 10 ppm NO2. In the 5 ppm short- and long-term exposure groups the pulmonary arterial medial thickness was significantly decreased compared to controls. Correlation analysis revealed a negative correlation between average medial thickness and alveolar surface density (coefficient of correlation: -0.56). We conclude that the extent of NO2-induced pulmonary parenchymal and vascular alterations are closely related and concentration- and time-dependent.

Topics: Animals; Dose-Response Relationship, Drug; Lung; Male; Nitrogen Dioxide; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Emphysema; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Time Factors

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

Topics: Administration, Inhalation; Animals; Collagen; Desmosine; Disease Models, Animal; DNA; Elastin; Environmental Exposure; Hydroxyproline; Lung; Male; Nitrogen Dioxide; Ozone; Proteins; Pulmonary Fibrosis; Pyridines; Rats; Rats, Sprague-Dawley; Survival Rate

The biologic impact of consecutive exposures to two environmental pollutants was examined in mice exposed to silica crystals (SI) by intratracheal (IT) injection followed by an inhalation exposure to nitrogen dioxide (NO2). C57Bl/6 mice received an IT injection of 2 mg SI or sterile saline (SAL) followed by a 2-h inhalation exposure to NO2 at 20 ppm either within 2 h of or 24 h after SI instillation. During acute inflammation (d 3 postsilica), mice exposed to NO2 at either time showed a dramatic and significant reduction in the number of lavaged alveolar neutrophils (PMN) when compared to silica/air-exposed mice. Animals exposed to NO2 24 h after silica also evidenced significant decreases in levels of lavage albumin and lactate dehydrogenase (LDH) 3 d after silica, as well as significant decreases in hydroxyproline content of the lung 30 and 60 d postsilica injection when compared to silica/air-exposed animals. NO2 administration 24 h after silica appeared to shift the appearance of PMN in the lung from d 3 to d 14, but did not otherwise alter chronic cellular inflammation. These data suggest that the marked neutrophil response and collagen deposition induced by SI can be modulated by NO2 exposure and that the time of oxidant gas exposure after silica administration is critical to this modulation.

Topics: Acute Disease; Air Pollutants; Albumins; Animals; Biomarkers; Chronic Disease; Collagen; Drug Interactions; Female; L-Lactate Dehydrogenase; Lung; Mice; Mice, Inbred C57BL; Neutrophils; Nitrogen Dioxide; Oxidants; Pneumonia; Proteins; Pulmonary Alveoli; Pulmonary Fibrosis; Silicon Dioxide; Time Factors

Topics: Adult; Air Pollutants, Occupational; Biopsy; Humans; Male; Nitrogen Dioxide; Occupational Diseases; Pulmonary Alveoli; Pulmonary Fibrosis

A search of 3600 indexed pathology cases has disclosed pulmonary fibrosis in 29 welders. Scanning electron microscopy of biopsy material revealed macrophages laden with inorganic particulates which have characteristics compatible with welding aerosols. In order to establish a possible relationship between fibrotic reaction and welding-fume exposure, the fibrogenic potential fo some 11 different welding fumes and metallic aerosols, considered to be reference standard surrogates for the commonly used welding technologies and applications responsible for 70% of welders exposure, were screened using the Rat Peritoneal Macrophage in vitro bioassay. Only one class of fumes, that from the manual metal arc welding of stainless steel, showed distinct fibrogenic potential. This fume is, however, not common to more than four or five of the heretofore 90 cases of pulmonary fibrosis reported among welders. Thus, although insoluble Cr(VI) is probably the active fibrogen in stainless steel fumes, an etiological factor common to all fibrogenic welding exposures must be sought. It is tentatively proposed to be NO2, a potential experimental in vivo fibrogen copiously produced by certain welding processes and ubiquitous at low concentrations in the welding environment.

Topics: Adult; Aged; Animals; Chromium; Humans; In Vitro Techniques; Macrophages; Middle Aged; Mutagens; Nitrogen Dioxide; Occupational Diseases; Pulmonary Fibrosis; Rats; Risk; Solubility; Welding

Topics: Animals; Bronchitis; Carbon; Cytoplasm; Epithelium; Hyperplasia; Indicators and Reagents; Intubation, Intratracheal; Lung; Macrophages; Male; Microscopy; Microscopy, Electron; Necrosis; Nitrates; Nitrogen Dioxide; Phagocytosis; Pneumonia; Pulmonary Alveoli; Pulmonary Fibrosis; Rats; Staining and Labeling

Topics: Aging; Animals; Body Weight; Bronchi; Elastic Tissue; Lung Diseases; Nitrogen Dioxide; Organ Size; Pulmonary Alveoli; Pulmonary Fibrosis; Rats; Staining and Labeling; Time Factors

Topics: Air Pollution; Animals; Bronchial Diseases; Bronchitis; Bronchopneumonia; Dogs; Guinea Pigs; Lung; Lung Diseases; Mice; Nitrogen Dioxide; Pathology; Poisoning; Pulmonary Edema; Pulmonary Fibrosis; Rabbits; Rats; Research; Toxicology; Tracheitis