• Biomedical Science Letters
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• v.20 no.1
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• pp.8-13
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• 2014

Occupational long-term exposure to inorganic dusts may cause a variety of lung diseases such as pneumoconiosis and chronic obstructive pulmonary disease (COPD). Diagnosis of pneumoconiosis and COPD, however, is currently dependent on radiological findings and pulmonary test, which are both late diagnostic tools. Therefore, there is a need to identify novel biomarkers in pneumoconiosis and COPD. Hence, in this current study we investigated the serum concentrations of YKL-40, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-${\alpha}$) as biomarkers for pneumoconiosis and COPD in 161 retired male workers exposed to inorganic dusts. The serum concentration of YKL-40 was significantly increased with age, pneumoconiosis, and airflow limitation. The serum concentration of IL-6 was significantly higher in airflow limitation. These results suggest that serum concentration of YKL-40 is associated with age, pneumoconiosis, and airflow limitation. Also, serum concentration of IL-6 is associated with airflow limitation.

• Tuberculosis and Respiratory Diseases
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• v.70 no.4
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• pp.323-329
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• 2011

Background: Although patients with tuberculous-destroyed lung (TDL) account for a significant proportion of those with chronic airflow obstruction, it is difficult to distinguish patients with airway obstruction due to TDL from patients with pure chronic obstructive pulmonary disease (COPD) on initial presentation with dyspnea. We investigated clinical features differing between (i) patients with TDL and airway obstruction and (ii) those with COPD admitted to the intensive care unit (ICU) due to dyspnea. Methods: We reviewed the medical records of patients with TDL who had a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70% on a pulmonary function test (PFT; best value closest to admission) and patients with COPD without a history of pulmonary tuberculosis (TB) who were admitted to the ICU. Ultimately, 16 patients with TDL and 16 with COPD were compared, excluding patients with co-morbidities. Results: The mean ages of the patients with TDL and COPD were 63.7 and 71.2 years, respectively. Mean FVC% (50.4% vs. 71.9%; p<0.01) and mean FEV1% (39.1% vs. 58.4%; p<0.01) were significantly lower in the TDL group than in the COPD group. More frequent consolidation with TB (68.8% vs. 31.3%; p=0.03) and more tracheostomies (50.0% vs. 0.0%; p=0.02) were observed in the TDL than in the COPD group. Conclusion: Upon ICU admission, patients with TDL had TB pneumonia more frequently, more diminished PFT results, and more tracheostomies than patients with COPD.

• Journal of Pharmaceutical Investigation
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• v.40 no.4
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• pp.231-236
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• 2010

This study was to fabricate the porous poly(lactide-co-glycolide) (PLGA) microparticles with anthocyanin (as a model antioxidant) for pulmonary drug delivery. The highly porous PLGA microparticles were prepared by the waterin-oil-in-water ($W_1/O/W_2$) multi-emulsion method, followed by the decomposition of ammonium bicarbonate (AB) in $W_1$ phase to the base of ammonia, carbon dioxide and water vapor at $50^{\circ}C$, making a porous structure in PLGA microparticles. Herein, hyaluronate (HA), a viscous polysaccharide, was incorporated in the porous microparticles for sustained anthocyanin release. In in vitro release studies, the anthocyanin release from the porous microparticles with HA continued up to 24 hours, while the porous microparticles without HA released 80 wt.% of encapsulated anthocyanin within 2 hours. In addition, these microparticle are expected to be effectively deposited at a lung epithelium due to its high porosity (low density) and avoid alveolar macrophage's uptake in the lung due to its large particle size. We believe that this system has a great pharmaceutical potential as a long acting antioxidant for relieving the oxidative stress in chronic obstructive pulmonary disease (COPD).

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.481-492
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• 2020

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis. Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

• The Korean Journal of Nuclear Medicine
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• v.16 no.1
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• pp.1-6
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• 1982

To evaluate the usefulness of radionuclide cardiac angiography in the assessment of right ventricular function, we measured right ventricular ejection fraction (RVEF) using single pass method. In 12 normal persons, RVEF averaged $52.7{\pm}5.9%(mean{\pm}S.D.)$. In 25 patients with chronic obstructive lung disease, RVEF was $37.2{\pm}10.6%$ and significantly lower than that of normal persons (p<0.01). All 10 patients with right ventricular failure had abnormal RVEF, which was significantly lower than that of 14 patients without right ventricular failure ($27.6{\pm}5.7%,\;43.9{\pm}8.5%$, respectively. p<0.01). It concluded thal RVEF measured by single pass radionuclide cardiac angiography was a useful, noninvasive method to assess right ventricular function.

• Molecules and Cells
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• v.42 no.4
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• pp.333-344
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• 2019

Various genetic and environmental factors are known to be associated with chronic obstructive pulmonary disease (COPD). We identified COPD-related differentially expressed genes (DEGs) using 189 samples accompanying either adenocarcinoma (AC) or squamous cell carcinoma (SC), comprising 91 normal and 98 COPD samples. DEGs were obtained from the intersection of two DEG sets separately identified for AC and SC to exclude the influence of different cancer backgrounds co-occurring with COPD. We also measured patient samples named group 'I', which were unable to be determined as normal or COPD based on alterations in gene expression. The Gene Ontology (GO) analysis revealed significant alterations in the expression of genes categorized with the 'cell adhesion', 'inflammatory response', and 'mitochondrial functions', i.e., well-known functions related to COPD, in samples from patients with COPD. Multi-omics data were subsequently integrated to decipher the upstream regulatory changes linked to the gene expression alterations in COPD. COPD-associated expression quantitative trait loci (eQTLs) were located at the upstream regulatory regions of 96 DEGs. Additionally, 45 previously identified COPD-related miRNAs were predicted to target 66 of the DEGs. The eQTLs and miRNAs might affect the expression of 'respiratory electron transport chain' genes and 'cell proliferation' genes, respectively, while both eQTLs and miRNAs might affect the expression of 'apoptosis' genes. We think that our present study will contribute to our understanding of the molecular etiology of COPD accompanying lung cancer.

• Biomolecules & Therapeutics
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• v.28 no.3
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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.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.55-61
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• 1992

Background: The lung is the most common site of metastasis and usually it manifests as a single or multiple nodules in chest X-ray. But less commonly the cancer spreads through the lymphatics and X-ray shows diffuse reticulonodular densities. Sometimes, patient is presented with respiratory symptoms only with interstitial lung infiltration before the signs of primary tumor and in that cases, the differential diagnosis with other interstitial lung disease is required. We have experienced 5 such cases, who were diagnosed as lymphangitic carcinomatosis by transbronchial lung biopsy. Methods: Clinical manifestation, pulmonary function test, modified thin section CT, bronchoalveolar lavage and transbronchial lung biopsy were done. Results: The primary tumor was gastric cancer in 3, lung cancer in 2. Pulmonary function test showed restrictive pattern with low DLco in 2 patients and obstructive pattern in one. Bronchoalveolar lavage showed lymphocytosis in 4 patients and malignant cells were found in one patient. Transbronchial lung biopsy revealed malignant cells localized to the lymphatics (peribronchial, perivascular and perialveolar). Cell type was adenocarcinoma in 4 and squamous cell carcinoma in one. Conclusion: Rarely lymphangitic carcinomatosis can be presented as diffuse interstitial lung disease and easily diagnosed by transbronchial lung biopsy.

• Journal of Chest Surgery
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• v.26 no.7
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• pp.532-537
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• 1993

To assess the therapy of spontaneous pneumothorax in the aged patients, the treatment methods and results in 60 patients 50 years of age or older were retrospectively reviewed. Most of the patients were male [56 of 60 patients] and the major underlying lung diseases associated with spontaneous pneumothorax were tuberculosis [32 patients] and chronic obstructive lung disease [20 patients]. The recurrence rate of thoracostomy tube drainage with or without chemical pleurodesis using tetracycline was 39.6% [21 of 53 patients], but there was no recurrence in the patients treated with open thoracotomy, pleural abrasion, and chemical pleurodesis using talcum powder[Asbestosis free]. In the patients treated with open thoracotomy, the bullous or bleb lesions were placed in the various sites of both lungs. We concluded that even though thoracostomy tube drainage is the first choice of therapy for spontaneous pneumothorax in the aged patients, the recurrence rate is high, especially in the patients with persistent air leakage for more than 2 days, and the open thoracotomy with pleural abrasion and chemical pleurodesis using talcum powder can prevent the recurrence in the selected patients.

• Tuberculosis and Respiratory Diseases
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• v.79 no.1
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• pp.22-30
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• 2016

Background: The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting ${\beta}2$-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods: Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the step-down group and as 1 year after the start of triple therapy in the triple group. Results: Lung function at the index time was superior and the previous exacerbation frequency was lower in the step-down group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second ($FEV_1$) decline ($54.7{\pm}15.7mL/yr$ vs. $10.7{\pm}7.1mL/yr$, p=0.007), but there was no observed increase in the frequency of exacerbations. Conclusion: Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating $FEV_1$ decline.