• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.260-267
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• 2000

Giant cell interstitial pneumonia. a synonym for hard metal pneumoconiosis, is a unique form of pulmonary fibrosis resulting from an exposure to hard metal dust. A case of biopsy-proved giant cell interstitial pneumonia in the absence of appropriate history of exposure to hard metal dust is reported. The patient presented with clinical features of chronic interstitial lung disease or idiopathic pulmonary fibrosis. He worked in a chemical laboratory at a fertilizer plant, where he had been exposed to various chemicals such as benzene and toluene. He denied having any other hobby in his house or job at work, which may have exposed him hard metal dust. High-resolution CT scan revealed multi-lobar distribution of ground glass opacity with peripheral and basal lung predominance. The retrieved fluid of bronchoalveolar lavage contained asbestos fiber and showed neutrotphil predominance. Surgical lung biopsy was performed for a definite diagnosis. Lung specimen showed alveolar infiltration of numerous multinucleated giant cells with mild interstitial fibrosis. Upon detailed examination of the lung tissue, one asbestos body was found. An analysis for mineral contents in lung tissue was performed. Compared with the control specimen, the amount of cobalt and several hard metal components in the lung tissue of this patient was ten times higher. We speculated that the inconsistency between occupational history and the findings of pathologic and mineralogical analyses could be explained by the difference in individual immunologic reactivity to hard metal dust despite the relatively small amount of unrecognized environmental exposure(ED: It's hard to understand what this phrase is trying to say).

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1137-1142
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• 2018

Background/Aims: This study tested the hypothesis that prolonged low-dose cyclophosphamide (CTX) treatment after pulse therapy attenuate paraquat (PQ)-induced lung injury in rats. Methods: PQ (25 mg/kg) was administered intraperitoneally to induce PQ-intoxicated rat model. The rats were randomly divided into four groups: control group (1 mL/day saline solution for 14 days), PQ group (1 mL/day saline solution for 14 days after PQ exposure), pulse group (15 mg/kg/day CTX in 1 mL of saline solution for 2 days and subsequent 1 mL/day saline solution for 12 days), and prolonged low-dose group (15 mg/kg/day CTX in 1 mL of saline solution for 2 days and subsequent 1.5 mg/kg/day CTX in 1 mL of saline solution for 12 days). A 14-day follow-up was conducted to determine the survival rat, and lung hydroxyproline (HYP), wet-to-dry weight ratios (W/Dc) and histopathological changes were evaluated. Results: Results showed similar survival rate (55% vs. 50%, p > 0.05) between prolonged low-dose and pulse groups. Lung W/Dc ($4.94{\pm}0.38$ vs. $5.47{\pm}0.28$, p < 0.01), HYP ($3.34{\pm}0.29{\mu}g/mg$ vs. $3.65{\pm}0.19{\mu}g/mg$, p < 0.001), and fibrosis score ($2.69{\pm}0.84$ vs. $3.13{\pm}0.63$, p < 0.05) were lower in prolonged low-dose group than those in the pulse group. Conclusions: These findings suggested prolonged low-dose CTX treatment after pulse therapy could attenuate PQ-induced lung injury in rats.

• Tuberculosis and Respiratory Diseases
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• v.85 no.4
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• pp.313-319
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• 2022

Environmental exposure to air pollution is known to have adverse effects on various organs. Air pollution has greater effects on the pulmonary system as the lungs are directly exposed to contaminants in the air. Here, we review the associations of air pollution with the development, morbidity, and mortality of pulmonary diseases. Short-and long-term exposure to air pollution have been shown to increase mortality risk even at concentrations below the current national guidelines. Ambient air pollution has been shown to be associated with lung cancer. Particularly long-term exposure to particulate matter with a diameter <2.5 ㎛ (PM_2.5) has been reported to be associated with lung cancer even at low concentrations. In addition, exposure to air pollution has been shown to increase the incidence risk of chronic obstructive pulmonary disease (COPD) and has been correlated with exacerbation and mortality of COPD. Air pollution has also been linked to exacerbation, mortality, and development of asthma. Exposure to nitrogen dioxide (NO₂) has been demonstrated to be related to increased mortality in patients with idiopathic pulmonary fibrosis. Additionally, air pollution increases the incidence of infectious diseases, such as pneumonia, bronchitis, and tuberculosis. Furthermore, emerging evidence supports a link between air pollution and coronavirus disease 2019 transmission, susceptibility, severity and mortality. In conclusion, the stringency of air quality guidelines should be increased and further therapeutic trials are required in patients at high risk of adverse health effects of air pollution.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.529-534
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• 2002

Interstitial pneumonia is a heterogenous group of inflammatory and fibrosing lesions that manifest themselves as infiltrative lung disease. Of these, nonspecific interstitial pneumonia is characterized as a variable degree of interstitial inflammation with or without fibrosis and is distinguished from usual interstitial pneumonia and desquamative interstitial pneumonia, histologically. The influx of inflammatory cells and the responses of immune effector cells injury to the alveolar wall and these initial injuries results in alveolitis and fibrosis. Consequently, the gas exchange throughout the alveolar wall is impaired and the patients suffer from lung diseases of a restrictive pattern. The chief complaints represented are dyspnea and dry cough. We experienced a case of nonspecific interstitial pneumonia in a 10-year old girl. The patient had been healthy and had not been exposed to organic dusts or other toxic materials. The pathology of lung biopsy tissue showed that the alveoli were thickened by a mixture of chronic inflammatory cells and collagen type fibrosis. High resolution computed tomography(HRCT) found the patchy areas of ground-glass opacity with patchy consolidation and irregular reticular opacity, and diffuse distribution without zonal predominance. The forced vital capicity(FVC) was 31%, forced expiratory volume in one second ($FEV_1$) 29% and $FEV_1/FVC$ 90%, so a restrictive pulmonary insufficiency was found.

• Journal of Chest Surgery
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• v.54 no.3
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• pp.191-199
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• 2021

Background: Tracheal replacement is a challenge for thoracic surgeons due to stenosis in the trachea-prosthesis anastomosis. We propose that stenosis occurs due to fibrosis as a result of an abnormal healing process, characterized by an increased expression of wound healing growth factors (vascular endothelial growth factor [VEGF], survivin, and CD31), which promote angiogenesis and decrease apoptosis. We analyzed the immunoreactivity of VEGF, survivin, CD31, and caspase-3 in the development of fibrotic stenosis in prosthetic tracheal replacement. Methods: Fourteen dogs were operated on: group I (n=7) received a 6-ring cervical tracheal segment autograft, while in group II (n=7), a 6-ring segment of the cervical trachea was resected and tracheal continuity was restored with a Dacron prosthesis. The follow-up was 3 months. Immunoreactivity studies for VEGF, survivin, CD31, and caspase-3 were performed. A statistical analysis was done using the Wilcoxon signed rank test. Results: Four animals in group I were euthanized on the 10th postoperative day due to autograft necrosis. Three animals completed the study without anastomotic stenosis. Moderate expression of VEGF (p=0.038), survivin (p=0.038), and CD31 (p=0.038) was found. All group II animals developed stenosis in the trachea-prosthesis anastomotic sites. Microscopy showed abundant collagen and neovascularization vessels. Statistically significant immunoreactive expression of VEGF (p=0.015), survivin (p=0.017), and CD31 (p=0.011) was observed. No expression of caspase-3 was found. Conclusion: We found a strong correlation between fibrosis in trachea-prosthesis anastomoses and excessive angiogenesis, moderate to intense VEGF, CD31, and survivin expression, and null apoptotic activity. These factors led to uncontrolled collagen production.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.437-447
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• 2001

Background: TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-induced lung fibrosis model. This study examined JNK activity in patients with UIP. Methods : The expression of phosphorous JNK(p-JNK), macrophage/monocyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical(IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchol-avleolar lavage from patients with UIP and healthy persons as the control. Results : The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/mL of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people. Conclusion : The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.136-147
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• 2002

Background : Interstitial lung disease has various manifestations that are differentiated by their pathology, progress and treatment. However, all manifestations eventually progresses to pulmonary fibrosis. Recent studies have shown that apoptosis of pulmonary epithelial cells might be related to pulmonary fibrosis. The correlation of the apoptotic index with the clinical manifestations, pathological findings, HRCT findings and the response to treatment were examined. Materials and Methods : Twenty subjects (14 men, 16 women), who had been diagnosed with interstitial lung disease through an open lung biopsy, were enrolled in this study. The subtypes were one AIP, two NIP, eight BOOP, and seven UIP cases. The apoptotic index was scaled from 0-2 depending on the fraction of positive staining cells by TUNEL method. The clinical severity was assessed by a modification of a previously developed CRP scoring system. The pathologic scores were based on 4 components: fibrosis, cellularity, desquamation, and granulation. In the HRCT study, each lobe was scored by the radiologists on a scale for both fibrosis and ground-glass attenuation. The treatment response was assessed by an increase in more than 10% of the CRP score, and comparing the results 3 months before and after treatment. Results : The apoptotic index showed no correlation with the CRP and HRCT scoring system. The apoptotic index correlated with the pathologic elements including fibrosis, cellularity and the desquamation score (p<0.05). Of the 16 patients who received corticosteroid therapy, 9 patients (56.3%) responded to therapy. There was no correlation between the response to corticosteroid and the apoptotic index. In the case of patients with acute and subacute ILD, the apoptotic index showed a correlation with the cellularity, desquamation, and the total histological score (p<0.05). In the case of patients with chronic ILD, the apoptotic index correlated with the fibrosis and cellularity score (p<0.05). Conclusion : Apoptosis of the pulmonary epithelial cells is implicated in the pathogenesis of interstitial lung disease particularly on a pathological basis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.493-498
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• 2001

Lung involvement in systemic sclerosis(SSC) is common but usually occurs late in the course. Skin changes usually occur before the pulmonary findings. In this report, a patient who developed pulmonary interstitial fibrosis without skin changes is presented. A diagnosis of SSC lung involvement was made histologically. The a nti-scl-70 antibody test was positive. Esophageal manometry revealed a lower amplitude in the lower two-third of the esophagus and pressure in the lower esophageal sphincter. Here we report a case of systemic sclerosis sine scleroderma presenting as pulmonary interstitial fibrosis with a review of the relevant literatures.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.484-495
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• 2023

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

• Journal of Yeungnam Medical Science
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• v.36 no.1
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• pp.8-15
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• 2019

Connective tissue diseases (CTDs) can affect all compartments of the lungs, including airways, alveoli, interstitium, vessels, and pleura. CTD-associated lung diseases (CTD-LDs) may present as diffuse lung disease or as focal lesions, and there is significant heterogeneity between the individual CTDs in their clinical and pathological manifestations. CTD-LDs may presage the clinical diagnosis a primary CTD, or it may develop in the context of an established CTD diagnosis. CTD-LDs reveal acute, chronic or mixed pattern of lung and pleural manifestations. Histopathological findings of diverse morphological changes can be present in CTD-LDs airway lesions (chronic bronchitis/bronchiolitis, follicular bronchiolitis, etc.), interstitial lung diseases (nonspecific interstitial pneumonia/fibrosis, usual interstitial pneumonia, lymphocytic interstitial pneumonia, diffuse alveolar damage, and organizing pneumonia), pleural changes (acute fibrinous or chronic fibrous pleuritis), and vascular changes (vasculitis, capillaritis, pulmonary hemorrhage, etc.). CTD patients can be exposed to various infectious diseases when taking immunosuppressive drugs. Histopathological patterns of CTD-LDs are generally nonspecific, and other diseases that can cause similar lesions in the lungs must be considered before the diagnosis of CTD-LDs. A multidisciplinary team involving pathologists, clinicians, and radiologists can adequately make a proper diagnosis of CTD-LDs.