• Tuberculosis and Respiratory Diseases
• /
• v.80 no.3
• /
• pp.247-254
• /
• 2017

Background: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. Methods: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. Results: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. Conclusion: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

• IMMUNE NETWORK
• /
• v.24 no.2
• /
• pp.3.1-3.23
• /
• 2024

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68⁺ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO^-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

• Tuberculosis and Respiratory Diseases
• /
• v.80 no.3
• /
• pp.277-283
• /
• 2017

Background: Smoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD. Methods: We included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment. Results: The median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036-1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376-29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388-34.998; p=0.018) were related to moderate to high nicotine dependence. Conclusion: Nicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.

• Journal of Chest Surgery
• /
• v.30 no.9
• /
• pp.941-944
• /
• 1997

Pulmonary infarction is rarely diagnosed with certainty except at postmortem examination. Part of this uncertainty is because of the inability to distinguish between hemorrhage, congestive a electasis, and necrosis clinically and radiographically. The pathogenesis of pulmonary infarction is poorly understood. It is dif%cult to induce pulmonary infarction in animals by ligation of the arterial supply to the lung. Many factors seem to be important in its pathogenesis, in addition to congestive heart failure, malignant tumor, thrombophlebitis, chronic obstructive lung disease, nephrotic syndrome, and postopeiative state. However, pulmonary infarction have not been reported in association with chest trauma. We report a case of pulmonary infarction associated with fractures of right clavicle and multiple ribs. A 45-year-old male had admitted due to right chest pain and dyspnea, which developed after right chest trauma occurred at about 3 weeks ago. He was treated at local clinics under the diagnosis of fractures of right clavicle and ribs until the admission. Chest CT disclosed a huge mass with central low density in right upper lobe, and small masses were also seen on both l ng fields. Open lung biopsy resulted in negativity for the malignancy. Clinical symptoms and radiological findings were not improved by conservative treatment. Right upper lobectomy was done eventually. The final diagnosis was pulmonary infarction. And, the patient has been well after operation.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.5
• /
• pp.571-575
• /
• 2006

Mycobacterium avium has been traditionally described as an opportunistic organism that causes disseminated disease in human immunodeficiency virus-positive patients and acts as a pulmonary pathogen in patients with underlying lung diseases such as chronic obstructive pulmonary disease or previously treated tuberculosis. Infections caused by M. avium in immunocompetent hosts usually manifest as 2 distinct subtypes, the upper lobe cavitary form and the nodular bronchiectatic form. However endobronchial lesions due to M. avium infections in immunocompetent host are reasonably rare, and there are no reports of this condition in Korea. We report here a case of endobronchial lesions involved in an M. avium infection in an immunocompetent 21 year-old female patient with no preexisting lung disease.

• Sleep Medicine and Psychophysiology
• /
• v.6 no.1
• /
• pp.19-25
• /
• 1999

Sleep alters both breathing pattern and the ventilatory responses to external stimuli. These changes during sleep permit the development or aggravation of sleep-related hypoxemia in patients with respiratory disease and contribute to the pathogenesis of apneas in patients with the sleep apnea syndrome. Fundamental effects of sleep on the ventilatory control system are 1) removal of wakefulness input to the upper airway leading to the increase in upper airway resistance, 2) loss of wakefulness drive to the respiratory pump, 3) compromise of protective respiratory reflexes, and 4) additional sleep-induced compromise of ventilatory control initiated by reduced functional residual capacity on supine position assumed in sleep, decreased $CO_2$ production during sleep, and increased cerebral blood flow in especially rapid eye movement(REM) sleep. These effects resulted in periodic breathing during unsteady non-rapid eye movement(NREM) sleep even in normal subjects, regular but low ventilation during steady NREM sleep, and irregular breathing during REM sleep. Sleep-induced breathing instabilities are divided due primarily to transient increase in upper airway resistance and those that involve overshoots and undershoots in neural feedback mechanisms regulating the timing and/or amplitude of respiratory output. Following ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include 1) hypocapnia, 2) inhibitory effect from lung stretch, 3) baroreceptor stimulation, 4) upper airway mechanoreceptor reflexes, 5) central depression by hypoxia, and 6) central system inertia. While the respiratory control system functions well during wakefulness, the control of breathing is commonly disrupted during sleep. These changes in respiratory control resulting in breathing instability during sleep are related with the pathophysiologic mechanisms of obstructive and/or central apnea, and have the therapeutic implications for nocturnal hypoventilation in patients with chronic obstructive pulmonary disease or alveolar hypoventilation syndrome.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.29 no.3
• /
• pp.404-413
• /
• 2019

Objectives: Chronic obstructive pulmonary disease(COPD) is an important cause of mortality in workers exposed to hazardous dust, such as crystalline silica or coal, and COPD is related to inflammation and oxidative stress in the lung. The aim of this study was to evaluate the association of oxidative stress and inflammation to COPD in retired workers exposed to mineral dust. Methods: The levels of malondialdehyde(MDA) in EBC as biomarkers for oxidative stress and C-reactive protein(CRP) and lactate dehydrogenase(LD) as biomarkers for inflammation were measured in 107 male subjects(63 pneumoconiosis and 42 COPD subjects). Results: Mean levels of EBC MDA(2.03 nmol/L vs. 4.65 nmol/L, p=0.010) and serum LD(170.3 U/L vs. 185.9 U/L, p=0.022) were significantly higher in subjects with COPD, but mean levels of serum CRP(p=0.469) did not show a statistical difference between the study groups. Level of EBC MDA was negatively correlated with ${%}FEV_1$ predicted(r=-0.279, p=0.004) and ${%}FEV_1/FVC$ ratio(r=-0.397, p<0.001). Conclusions: These results suggest that EBC is a useful biological matrix for investigation of respiratory oxidative stress. High levels of EBC MDA and serum LD are related to COPD in retired workers exposed to mineral dust.

• Laboraroty Animal Research
• /
• v.33 no.2
• /
• pp.76-83
• /
• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• Yonsei Medical Journal
• /
• v.59 no.9
• /
• pp.1079-1087
• /
• 2018

Purpose: Obstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease (CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however, underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS can lead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the intervention effects of antioxidant tempol. Materials and Methods: Male Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia (IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed in OS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh blood were harvested for analysis of endothelial markers and apoptosis. Results: The levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelial cells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group, and were lower in OST group than in OS and OSN groups (all p<0.001). Conclusion: Synergistic effects of IH with cigarette smoke-induced emphysema produce a greater inflammatory status and endothelial apoptosis. OS-related inflammation and endothelial cell apoptosis may play important roles in promoting cardiovascular dysfunction, and antioxidant tempol could achieve a partial protective effect.

• Tuberculosis and Respiratory Diseases
• /
• v.70 no.6
• /
• pp.516-520
• /
• 2011

Bronchial carcinoid tumor accounts for less than 5% of all primary lung tumors in adults. Although surgical resection is the treatment of choice, here we report a case of bronchial carcinoid tumor treated with flexible bronchoscopic resection. A 19-year-old-man presented with a history of wheezing with dyspnea for six months. A simple chest x-ray showed no abnormal findings, but a pulmonary function test showed a moderate obstructive lung disease pattern without a bronchodilator response. A computed tomogram of the thorax revealed an enhanced $15{\times}12$ mm nodule in the left main bronchus. Bronchoscopic examination showed a polypoid mass with a stalk in the left main bronchus, which almost completely occluded the left main bronchus. Histopathology of the resected specimen revealed a bronchial carcinoid tumor. We treated the carcinoid tumor with a flexible bronchoscopic resection. During the follow up period of 6 months, the previous tumor didn't relapse. Initial bronchoscopic resection should be considered when bronchial carcinoid tumor can be approached by bronchoscopy.