• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.239-245
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• 2015

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

• Tuberculosis and Respiratory Diseases
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• 제77권3호
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• pp.116-123
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• 2014

Background: Mesenchymal stem cells (MSCs) obtained from bone marrow or adipose tissue can successfully repair emphysematous animal lungs, which is a characteristic of chronic obstructive pulmonary disease. Here, we describe the cellular distribution of MSCs that were intravenously injected into mice with elastase-induced emphysema. The distributions were also compared to the distributions in control mice without emphysema. Methods: We used fluorescence optical imaging with quantum dots (QDs) to track intravenously injected MSCs. In addition, we used a human Alu sequence-based real-time polymerase chain reaction method to assess the lungs, liver, kidney, and spleen in mice with elastase-induced emphysema and control mice at 1, 4, 24, 72, and 168 hours after MSCs injection. Results: The injected MSCs were detected with QD fluorescence at 1- and 4-hour postinjection, and the human Alu sequence was detected at 1-, 4- and 24-hour postinjection in control mice (lungs only). Injected MSCs remained more in mice with elastase-induced emphysema at 1, 4, and 24 hours after MSCs injection than the control lungs without emphysema. Conclusion: In conclusion, our results show that injected MSCs were observed at 1 and 4 hours post injection and more MSCs remain in lungs with emphysema.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.250-258
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• 2020

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A₃ receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A₃ receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

• 대한핵의학회지
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• 제24권2호
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• pp.229-236
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• 1990

Perfusion and ventilaion imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonry emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebulizer with 15 mCi of Tc-99m-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with $^{99m}Tc-MAA$ was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary emphysema was diffuse (6/21), discrete(6/21), intermediate (3/21), or combined (6/21). In 12 patients studied also with perfusion scans, perfusion defects matched closely with ventilation defects in location and configuration. But the size of the ventilation defects was generally larger than the perfusion defects. In all four patients treated with bronchodilators, the follow-up study demonstrated decrease in abnormal of radioaerosol deposition in the central airway with improvement of ventilation defects. RII was useful technique for the evaluation of regional ventilatory abnormality and the effects of treatment with bronchodilators in pulmonary emphysema.

• Journal of Chest Surgery
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• 제27권10호
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• pp.882-884
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• 1994

Congenital lobar emphysema is one of the abnormal development of pulmonary parenchyme which may cause respiratory distress in infant. This disease is an unusual condition barely mentioned before 1949, and only 166 cases were reported till 1967 in English literature. This report describes a 13 months old girl who had a congenital left upper lobar emphysema. The left upper lobectomy was the operation for this case and the postoperative course was not eventful, and have been in good condition upto now.

• Korean Journal of Radiology
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• 제22권10호
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• pp.1719-1729
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• 2021

Objective: Emphysema and small-airway disease are the two major components of chronic obstructive pulmonary disease (COPD). We propose a novel method of quantitative computed tomography (CT) emphysema air-trapping composite (EAtC) mapping to assess each COPD component. We analyzed the potential use of this method for assessing lung function in patients with COPD. Materials and Methods: A total of 584 patients with COPD underwent inspiration and expiration CTs. Using pairwise analysis of inspiration and expiration CTs with non-rigid registration, EAtC mapping classified lung parenchyma into three areas: Normal, functional air trapping (fAT), and emphysema (Emph). We defined fAT as the area with a density change of less than 60 Hounsfield units (HU) between inspiration and expiration CTs among areas with a density less than -856 HU on inspiration CT. The volume fraction of each area was compared with clinical parameters and pulmonary function tests (PFTs). The results were compared with those of parametric response mapping (PRM) analysis. Results: The relative volumes of the EAtC classes differed according to the Global Initiative for Chronic Obstructive Lung Disease stages (p < 0.001). Each class showed moderate correlations with forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC) (r = -0.659-0.674, p < 0.001). Both fAT and Emph were significant predictors of FEV₁ and FEV₁/FVC (R² = 0.352 and 0.488, respectively; p < 0.001). fAT was a significant predictor of mean forced expiratory flow between 25% and 75% and residual volume/total vital capacity (R² = 0.264 and 0.233, respectively; p < 0.001), while Emph and age were significant predictors of carbon monoxide diffusing capacity (R² = 0.303; p < 0.001). fAT showed better correlations with PFTs than with small-airway disease on PRM. Conclusion: The proposed quantitative CT EAtC mapping provides comprehensive lung functional information on each disease component of COPD, which may serve as an imaging biomarker of lung function.

• Tuberculosis and Respiratory Diseases
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• 제80권1호
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• pp.83-89
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• 2017

Background: Previous studies report that apoptosis and autophagy are involved in the pathogenesis of emphysema, and macroautophagy is one of the processes regulating the apoptosis pathway. However, few studies have evaluated whether chaperone-mediated autophagy (CMA) contributes to the regulation of apoptosis. In this study, we investigated the impact of autophagy, including both macroautophagy and CMA, on the apoptosis in bronchial epithelial cells. Methods: Cigarette smoke extract (CSE) was injected intratracheally into C57BL/6 mice, and emphysema and apoptosis were evaluated in the lungs. After treatment with CSE, apoptosis, macroautophagy, and CMA were measured in BEAS2-B cells, and the impact of autophagy on the apoptosis was evaluated following knockdown of autophagy-related genes by short interfering RNAs (siRNAs). Results: Intratracheal CSE injection resulted in the development of emphysema and an increase in apoptosis in mice. CSE increased the apoptosis in BEAS2-B cells, and also elevated the expression of proteins related to both macroautophagy and CMA in BEAS2-B cells. The knockdown experiment with siRNAs showed that macroautophagy increases apoptosis in BEAS2-B cells, while CMA suppresses apoptosis. Conclusion: The intratracheal injection of CSE induces pulmonary emphysema and an increase in apoptosis in mice. CSE also induces apoptosis, macroautophagy, and CMA of bronchial epithelial cells. Macroautophagy and CMA regulate apoptosis in opposite directions.

• Journal of Chest Surgery
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• 제9권1호
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• pp.78-82
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• 1976

Bullous emphysema is usually associated with extensive chronic obliterative pulmonary disease. It is the disease of old age but rare in children or infancy. The bulla in this disease is acquired one. In general the symptoms are due to not the mere presence of the bulla but the extent of underlying lung pathology as emphysema or bronchitis. Occassionally giant bulla of great size may cause symptoms and in this occassion it should be differentiated from other diseases. Especially in children or infancy pneumothorax, congenital pulmonary cyst of lobar obstructive-emphysema should be excluded. Recently we experienced 2 cases of bullous emphysema in infancy with severe respiratory symptoms because of bullae of great size. We felt difficulties in differentiating with other conditions. The purpose of this report is to review our cases thoroughly and enhance considerations of this disease.

• Tuberculosis and Respiratory Diseases
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• 제50권4호
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• pp.415-425
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• 2001

배 경 : 폐기종의 중증도 판정에 있어서 병리학적 기준은 기강(air space)의 확장 정도에 있으며, 이는 고해상도 전산화 촬영 (high resolution computed tomography, HRCT)에 의해 결정되는 폐기종 점수(emphysema scoring)와 좋은 상관성을 보인다는 것은 주지의 사실이다. 한편 폐기종의 주증상은 운동성 호흡곤란이므로 폐기종에 대한 임상적 평가는 운동능력의 감소를 측정하는 것이 타당하다고 알려져 있다. 그러나 대개의 경우 폐기종의 중증도 판정은 안정시 폐기능 검사에 의존하는 경우가 흔하며, 병리학적 중증도 판정과 상관성이 높다고 알려져 있는 고해상도 전산화 촬영에 의한 폐기종 점수와 운동부하 폐기능검사 지표들과의 상관성 여부에 대한 연구는 드문 실정이다. 이에 본 연구에서는 폐기종의 중증도 판정에 있어서 HRCT와 안정시 폐기능 검사 및 운동부하 폐기능 검사간에 상호 관련성을 확인하여 보았다. 방 법 : 평균 연령 $60.6{\pm}10.3$세인 14명의 폐기종 환자들을 대상으로 HRCT, 안정시 폐기능 검사(forced expiratory flow volume curve, lung volumes by He dilution method, DLco, ABGA), 그리고 점진적운동부하폐 기능검사(incremental cycle ergometer)를 시행하였으며 HRCT는 GE highlight를 이용하여 조영증강 없이 최대흡기시에 1.5mm collimation, 10mm 간격으로 폐전체를 스캔하였고, 환자마다 모든 스캔에서 density mask를 이용하여 -400 HU를 기준으로 한 총폐면적과 -900 HU를 기준으로 한 폐기종 면적을 각각 구하여 백분율로 환산하여 폐기종 점수를 구하였다. 결 과 : 평균 폐기종 점수는 $37.4{\pm}14.9%$ 이었다. 폐기종 점수와 안정시 폐기능 검사의 DLco(r=-0.75)와 $PaO_2$(r=-0.66) 사이에서만 유의한(p<0.05) 상관성이 관찰되었다. 반면 폐기종 점수와 운동부하폐기능 지표들간의 상관성은 최대 산소섭취량(r=-0.68), 혐기성 역치(V-slope method, r=-0.690), 최대운동부하(r=-0.74), 최대운동시 $O_2$ pulse(r=-0.73), 최대운동시의 생리적 사강비율 (r=0.80) 등과 높은 유의성 (p<0.01)을 나타내었다. 그러나 호흡예비율과 심박수 예비율간에서는 유의한 상관성이 없었고, pulse oxymeter로 측정한 산소포화도와의 상관성도 유의하지 않았다. 결 론 : 이상의 결과에서 폐기종의 병리학적 중증도를 잘반영한다고 알려진 HRCT 폐기종 접수는 폐기종에 의한 생리학적 장애를 잘 반영하는 운동부하 폐기능 검사의 주요 지표들과 유의한 상관성이 있음을 확인할 수 있었다.

• 대한영상의학회지
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• 제85권4호
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• pp.714-726
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• 2024

흉부 CT상 폐기종이나 간질성 폐질환의 형태나 범위를 인공지능을 이용하여 자동적으로 객관적으로 진단하는 다양한 알고리즘을 개발되고, 이를 증명하는 연구들이 진행되어 왔다. 흉부 CT상 인공지능을 이용한 폐기종 정량화 연구들을 보면 CT상 폐기종의 상대적인 양이 증가와 폐 기능의 악화와 연관이 있으며, 특히 중심성 폐기종을 중심으로 정량화를 하는 것이 임상 증상이나 만성폐쇄성 폐질환의 사망률을 예측하는 데 도움이 된다고 보고하고 있다. 또한, 간질성 폐질환에서는 인공지능이 CT상 통상성 간질성 폐렴의 형태를 정상, 간유리 음영, 망상형 음영, 벌집 모양, 폐기종, 경화로 분류를 할 수 있고, 인공지능이 흉부영상의학과 전문의와 비슷한 정도로 통상성 간질성 폐렴을 진단(70%-80%) 할 수 있다고 보고했다. 그러나 인공지능의 결과들이 흉부 CT의 스캔 변수들, 재구성 알고리즘, 방사선 선량, 개발된 인공지능 훈련 데이터에 의해 영향을 받으며, 이러한 이유로 아직까지 흉부 CT상 폐기종과 간질성 폐질환의 진단과 정량화는 실제로 일상 업무에서 제한적으로 사용되고 있다. 이 논문에서는 폐기종과 간질성 폐질환의 진단과 정량화를 위해서 인공지능을 사용하고 있는 저자들의 경험을 증례로 소개를 하고, 이 두 질환의 인공지능의 효용성과 제한점에 대해서 언급하고자 한다.