• Clinical and Experimental Pediatrics
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• 제58권12호
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• pp.459-465
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• 2015

Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease.

• Tuberculosis and Respiratory Diseases
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• 제86권4호
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• pp.304-318
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• 2023

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

• Journal of Chest Surgery
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• 제24권4호
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• pp.338-344
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• 1991

If the postoperative pulmonary function can be predicted in the patients undergoing pneumonectomy for lung cancer preoperatively, it will be helpful for identifying them as high or low risk candidates. Perfusion lung scan and spirometry were performed in 12 patients with lung cancer pre-operatively and the predicted postoperative Vital Capacity, FVC, FEV1.0, FEF25 - 75% and MVV were estimated by multiplying the preoperative values by the percentage of perfusion of the nonsurgical lung. Three months postoperation the patients were reinvestigated with spirometry and the obtained values were compared with the predicted values. The linear regression lines derived from the correlation between predicted values [X] and observed values [Y] were as follows; VC; R=0.532, Y=0.48X+1.28, P=0.075 FVC; R=0.566, Y=O 54X+1.15, P=0.055 FEV1.0; R=0.832, Y=0.68X+0.70, P=0.001 FEF25 ~ 75%; R=0.781, Y=0.68X+0.54, P=0.003 MVV; R=0.718, Y=0.67X+34.75, P=0.009 The prediction of postoperative FEV1.0, FEF25 ~ 75% and MVV in lung cancer patients undergoing pneumonectomy appear to be valid for evaluating preoperative pulmonary function.

• Tuberculosis and Respiratory Diseases
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• 제86권3호
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• pp.203-215
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• 2023

Background: Surgical resection is the standard treatment for early-stage lung cancer. Since postoperative lung function is related to mortality, predicted postoperative lung function is used to determine the treatment modality. The aim of this study was to evaluate the predictive performance of linear regression and machine learning models. Methods: We extracted data from the Clinical Data Warehouse and developed three sets: set I, the linear regression model; set II, machine learning models omitting the missing data: and set III, machine learning models imputing the missing data. Six machine learning models, the least absolute shrinkage and selection operator (LASSO), Ridge regression, ElasticNet, Random Forest, eXtreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM) were implemented. The forced expiratory volume in 1 second measured 6 months after surgery was defined as the outcome. Five-fold cross-validation was performed for hyperparameter tuning of the machine learning models. The dataset was split into training and test datasets at a 70:30 ratio. Implementation was done after dataset splitting in set III. Predictive performance was evaluated by R² and mean squared error (MSE) in the three sets. Results: A total of 1,487 patients were included in sets I and III and 896 patients were included in set II. In set I, the R² value was 0.27 and in set II, LightGBM was the best model with the highest R² value of 0.5 and the lowest MSE of 154.95. In set III, LightGBM was the best model with the highest R² value of 0.56 and the lowest MSE of 174.07. Conclusion: The LightGBM model showed the best performance in predicting postoperative lung function.

• Journal of Chest Surgery
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• 제51권4호
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• pp.280-282
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• 2018

Unilateral absence of a pulmonary artery (UAPA) is a rare congenital anomaly that may present with various symptoms, depending on the nature and severity of other cardiovascular anomalies. Furthermore, contralateral lung surgery in patients with UAPA is extremely rare, and clinical experience is limited. This report describes a case of surgical treatment of contralateral primary lung cancer in a patient with isolated UAPA. A 56-year-old man was diagnosed with primary lung cancer accompanied by isolated UAPA on the contralateral side. He underwent meticulous cardiorespiratory function tests preoperatively. We performed a right lower lobectomy. Although in the immediate postoperative period, the patient suffered from a mild decline in his respiratory function, he recovered uneventfully. The present case shows that preoperative awareness of UAPA and meticulous perioperative management enable contralateral lung surgery to be performed safely.

• 멤브레인
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• 제14권1호
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• pp.18-25
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• 2004

본 연구의 목적은 정맥 내 폐 보조장치 설계에 있어서 기체전달을 예측하기 위하여 혈관 내 폐 보조장치를 정맥 내에 삽입하기 전, 여러 가지 설계조건에서 실험적 모델링을 통하여 예측식을 찾고자 시도하였다. 실험결과 중공사 충진율의 함수에 따라 기체전달을 예측할 수 있었다. 실험에 의하여 얻어진 기체전달은 예측식에 의한 기체전달과 유사하여, 식에 대한 신뢰성을 얻을 수 있었다. 그러므로, 중공사의 충진율의 함수에 따라 기체전달을 예측할 수 있으며, 혈관 내 폐 보조장치의 기체전달을 예측하는데 매우 유용하였다.

• Molecules and Cells
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• 제43권9호
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• pp.774-783
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• 2020

The lung has a vital function in gas exchange between the blood and the external atmosphere. It also has a critical role in the immune defense against external pathogens and environmental factors. While the lung is classified as a relatively quiescent organ with little homeostatic turnover, it shows robust regenerative capacity in response to injury, mediated by the resident stem/progenitor cells. During regeneration, regionally distinct epithelial cell populations with specific functions are generated from several different types of stem/progenitor cells localized within four histologically distinguished regions: trachea, bronchi, bronchioles, and alveoli. WNT signaling is one of the key signaling pathways involved in regulating many types of stem/progenitor cells in various organs. In addition to its developmental role in the embryonic and fetal lung, WNT signaling is critical for lung homeostasis and regeneration. In this minireview, we summarize and discuss recent advances in the understanding of the role of WNT signaling in lung regeneration with an emphasis on stem/progenitor cells.

• 대한이식학회지
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• 제28권3호
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• pp.154-159
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• 2014

Background: Lung transplantation (LTx) is a life-saving treatment for patients with end-stage lung disease; however, the shortage of donor lungs has been a major limiting factor to increasing the number of LTx. Growing experience following LTx using donor lungs after cardiac death (DCD) has been promising, although concerns remain. The purpose of this study was to develop a DCD lung harvest model using an ex vivo lung perfusion (EVLP) system and to assess the function of presumably damaged lungs harvested from the DCD donor in pigs. Methods: The 40 kg pigs were randomly divided into the control group with no ischemic lung injury (n=5) and the study group (n=5), which had 1 hour of warm ischemic lung injury after cardiac arrest. Harvested lungs were placed in the EVLP circuit and oxygen capacities (OC), pulmonary vascular resistance (PVR), and peak airway pressure (PAP) were evaluated every hour for 4 hours. At the end of EVLP, specimens were excised for pathologic review and wet/dry ratio. Results: No statistically significant difference in OC (P=0.353), PVR (P=0.951), and PAP (P=0.651) was observed in both groups. Lung injury severity score (control group vs. study group: 0.700±0.303 vs. 0.870±0.130; P=0.230) and wet/dry ratio (control group vs. study group: 5.89±0.97 vs. 6.20±0.57; P=0.560) also showed no statistically significant difference between the groups. Conclusions: The function of DCD lungs assessed using EVLP showed no difference from that of control lungs without ischemic injury; therefore, utilization of DCD lungs can be a new option to decrease the number of deaths on the waiting list.

• Journal of Chest Surgery
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• 제22권5호
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• pp.794-799
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• 1989

Sleeve lobectomy for bronchogenic carcinoma is an alternative to pneumonectomy. The extent and location of the tumor must be such that a sleeve procedure is feasible. The conservation of lung tissue benefits both compromised and uncompromised patients. From August 1988 to March 1989, five patients underwent sleeve lobectomy for bronchogenic carcinoma of the lung. The patients included four males and one female ranging in age from 52 years to 66 years. All patients were diagnosed as having squamous cell carcinoma. Operative procedures were right upper sleeve lobectomy in four cases and left upper sleeve lobectomy with pulmonary angioplasty in one case. Complications developed in one patient. An asthmatic attack necessitated ventilator support for one day. Bronchoscopic examinations were performed at two weeks and three months postoperatively in four patients. Anastomosis sites on all patients were intact, but in one case, nodules were noted. Pulmonary function tests were also checked at three months postoperatively, and showed good results. The reimplanted lobe or lobes contribute significantly to the overall remaining lung function. All patients are being followed up with satisfactory results, except one case of suspected local tumor recurrence. We think, therefore, that sleeve lobectomy is a safe and adequate procedure for patients with resectable lung cancer.