• Tuberculosis and Respiratory Diseases
• /
• v.86 no.1
• /
• pp.33-46
• /
• 2023

Background: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period. Methods: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 ㎍/25 ㎍) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician's evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement. Results: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (<0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment. Conclusion: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

• Korean Journal of Radiology
• /
• v.22 no.4
• /
• pp.634-651
• /
• 2021

Dynamic X-ray (DXR) is a functional imaging technique that uses sequential images obtained by a flat-panel detector (FPD). This article aims to describe the mechanism of DXR and the analysis methods used as well as review the clinical evidence for its use. DXR analyzes dynamic changes on the basis of X-ray translucency and can be used for analysis of diaphragmatic kinetics, ventilation, and lung perfusion. It offers many advantages such as a high temporal resolution and flexibility in body positioning. Many clinical studies have reported the feasibility of DXR and its characteristic findings in pulmonary diseases. DXR may serve as an alternative to pulmonary function tests in patients requiring contact inhibition, including patients with suspected or confirmed coronavirus disease 2019 or other infectious diseases. Thus, DXR has a great potential to play an important role in the clinical setting. Further investigations are needed to utilize DXR more effectively and to establish it as a valuable diagnostic tool.

• IMMUNE NETWORK
• /
• v.16 no.1
• /
• pp.75-84
• /
• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• The Korean Journal of Physiology
• /
• v.15 no.1
• /
• pp.37-43
• /
• 1981

In the present study, an effort was directed to elucidate the effect of the physical training on the pulmonary function. Twenty-four male athletics major students who have undergone regular physical training for more than five years were randomly chosen as the athletic subjects, and 12 regular male students who have not been engaged in any form of regular physical exercise or training were chosen as the non-athletic subjects, and a comparison was made between the two groups. The following were mainly observed by spirometry for the study; respiratory rate, tidal volume, vital capacity, maximum voluntary ventilation(MVV), forced expiratory volume for 1 second$(FEV_1)$, percent $FEV_1$ to forced vital capacity$(FEV_1%)$, forced expiratory flow for initial 1 liter$(FEF_{0.2-1.2}L)$, and forced mid-expiratory flow$(FEF_{\;25-75}%)$. The results obtained are summarized as follow. 1) The respiratory rate, tidal volume, and vital capacity showed no significant difference between athletes and non-athletes. The MVV in athletes was significantly (p<0.01) increased to $148.1{\pm}3.1\;L/min$ comparing with $118.3{\pm}9.1\;L/min$ in non-athletes. 2) $FEV_1$ was $3.310{\pm}0.070\;L$ in athletes and $2.779{\pm}0.104$ in non-athletes; $FEV_1%\;83.63{\pm}1.29%$ in athletes and $75.33{\pm}1.75%$ in non-athletes, both showing significant(p<0.01) increase in athletes. 3) $FEF_{0.2-1.2}L$ was $297.1{\pm}13.5\;L/min in athletes and $222.7{\pm}15.0\;L/min$ in non-athletes; $FEF_{\;25-75}%$ was $3.543{\pm}0.109\;L/sec$ in non-athletes, both showing significant(p<0.01) increase in athletes. 4) Some discussions were made on these results. The lung volumes showed no significant difference between the two groups. But MVV, $FEV_1$, $FEV_1%$, $FEF_{0.2-1.2}L$ and $FEF_{25-75}%$ in athletes were significantly(p<0.01) higher than in non-athletes. It is therefore concluded that the athletes have more powerful respiratory muscles, or higher compliance of the lung and thorax than the non-athletes.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.6
• /
• pp.619-627
• /
• 2004

Background : Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-${\gamma}1b$) therapy for IPF, as an antifibrotic agent. Methods : Medical records of 27 patients who were treated with IFN-${\gamma}1b$ (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-${\gamma}1b$ for more than 6 months. In addition, we compared the efficacy of IFN-${\gamma}1b$ therapy with that of cyclophosphamide${\pm}$prednisolone therapy (n=26). Results : The median age of IFN-${\gamma}$ treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, $55.4{\pm}11.3%$ vs. $70.7{\pm}10.9%$, p=0.019; DLco, $50.3{\pm}7.3%$ vs. $76.9{\pm}19.6%$, p=0.014). Lower baseline $PaO_2$ on room air breathing was observed in the deteriorated group ($68.6{\pm}7.8mmHg$ vs. $91.4{\pm}6.6mmHg$ p=0.001). Subcutaneous IFN-${\gamma}1b$ did not show better efficacy than prednisolone. Five patients discontinued IFN-${\gamma}$ because of severe side effects. ARDS developed in one patient, who eventually died. Conclusion : The administration of IFN-${\gamma}1b$ is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.

• Microbiology and Biotechnology Letters
• /
• v.32 no.1
• /
• pp.72-77
• /
• 2004

Previously, we synthesized a novel Cyclin-dependent kinase inhibitor, MCS-5A. Also, we investigated the involvement of cell cycle regulatory events during MCS-5A-mediated apoptosis in HL-60(+p16/-p53) cells with up-regulation of p16 protein expression. In contrast, apoptosis was not observed in A549(-p16/+p53) cells. Therefore we propose that $p16^{INK4A}$ is a key enzyme for inducing apoptosis. In the present studies, we have explored the mechanism of $p16^{INK4A}$ -mediated cytotoxicity and the role of p16.sup INK4A/ overexpression in the induction of apoptosis in human tumor cells. The tumor suppressor gene $p16^{INK4A}$ is known as a cyclin-dependent kinase inhibitor (CKI) and cell cycle regulator. We expressed wild type $p16^{INK4A}$ in pcDNA3.1 vector and then transfected into non-small cell lung cancer (NSCLC) cell expressing different statue of p16$^{INK4A}$, p53 gene〔A549(-p16/+p53), H1299(-p16/-p53) and HeLa(+pl6/+p53) cell line〕. TUNEL assay (including propidium iodide staining following transfection of these cell line with pcDNA3.1-pl6) indicate that p16$^{INK4A}$-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating an induction of caspase 3 cleavage due to the transfection of A549, H1299 and HeLa cells with pcDNA3.1-pl6. These results suggest that p16$^{INK4A}$ has a new function of inducing apoptosis which is not related with the function of tumor suppressor gene p53.

• Journal of Chest Surgery
• /
• v.34 no.9
• /
• pp.704-710
• /
• 2001

Background: Extracorporeal circulation using pump-oxygenator is an inevitable process to keep vital sign during cardiac arrest for open heart surgery. However, the diversion of blood through nonendothelialized channels appears to stimulate inflammatory response, and leukocyte activation may lead to cardiopulmonary edema. Our study evaluated the effect of leukocyte-induced cardiopulmonary edema using three different pump-oxygenator priming solutions; non-hemic crystalloid solution ; leukocyte-depleted homologous blood; non leukocyte-depleted homologous blood in priming solutions. Material and Method: Each different priming solution was used on five dogs, and the effect of leukocyte-induced cardiopulmonary edema during cardiopulmonary bypass(CPB) was evaluated. For each dog after 2 hours of exracorporeal circulation and another 4 hours of post-pump period, the dog was sacrificed and its heart and lung tissues were obtained for measuring Wet/Dry ratio. Arterial $O_2$partial pressure(PaO$_2$) and $CO_2$partial pressure(Pa$CO_2$) were checked. For the evaluation of ventilatory function, $CO_2$partial pressure difference between arterial blood (Pa$CO_2$) and exhaled air(Et$CO_2$) was measured. Result: 1. No significant difference was seen in arterial PaO$_2$and Pa$CO_2$among groups. 2. Ventilatory function evaluated by Pa$CO_2$and Et$CO_2$showed no significant difference between non-hemic and blood-mixed priming solution (P<0.05). 3. Cardiac and lung Wet/Dry ratios were remarkedly lower in the leukocyte-depleted group. There was no significant difference between the non-hemic and blood-mixed groups. Conclusion: Based upon this result, we concluded that the leukocyte depletion from homologous blood of CPB priming solution has a beneficial effect in reducing cardiopulmonary edema compared with non leukocyte-depleted or crystalloid priming solutions.

• Clinical and Experimental Pediatrics
• /
• v.51 no.8
• /
• pp.842-847
• /
• 2008

Purpose : Measurement of forced expiratory volume in 1 second ($FEV_1$) is usually difficult to obtain in children under six years of age because it requires active cooperation. This study evaluates the sensitivity of impulse oscillometry system (IOS) parameters for detecting airway obstruction in comparison with $FEV_1$. Methods : We studied 174 children who performed the lung function and methacholine challenge tests to diagnose asthma by IOS and spirometry. Children were divided into two subgroups according to their $PC_{20}$, which is a parameter for bronchial sensitivity. We compared IOS parameters with $FEV_1$ at the baseline, post-methacholine challenge, and evaluated their correlation. Results : At the baseline, reactance at 5 Hz (X5) and resistance at 5 Hz (R5) significantly differed between the $PC_{20}$ positive ($PC_{20}{\leq}16mg/mL$) group and $PC_{20}$ negative ($PC_{20}$ >16 mg/mL) group; however, $FEV_1$, $FEV_1$ % predicted, $FEV_1_-Zs$ (Z score) did not differ. $FEV_1$ is correlated with X5 (r=0.45, P<0.01) and R5 (r=-0.69, P<0.01). $FEV_1_-Zs$ is also correlated with X5_Zs (r=-0.26, P<0.01) and R5_Zs (r=-0.31, P<0.01). After the methacholine challenge test, dose-response slopes in $FEV_1$ and X5 significantly differed between the two subgroups (P<0.05). Conclusion : IOS parameters were more discriminative than $FEV_1$ for detecting decreased baseline lung function between two subgroups and have a good correlation with $FEV_1$.

• Reproductive and Developmental Biology
• /
• v.32 no.1
• /
• pp.51-58
• /
• 2008

This study was performed to investigate the relation between birth weight and survivability on the production of cloned Hanwoo calves. The 580 cloned embryos were transferred into the 293 recipients. The pregnancy rate of the cloned embryos was 72.3% at 50 days after embryo transfer, and then the rate was dramatically decreased. The mean gestation lengths were 287 days in both clone (range of$279{\sim}295$ days) and artificial insemination (AI, range of $255{\sim}293$ days) calves, respectively. The mean birth weight of cloned calves (30.3kg) was significantly higher compared to that of AI calves (23.7kg) (p<0.05). Among the cloned calves, the birth weight was not different in both normal delivery (n=17, 29.9kg) and caesarean section (n=14, 32.3kg). The weight, however, was significantly higher in the clones (n=18, 32.8kg) dead within 175 days than that of the clones (n=11, 28.3kg) alive more than 175 days after birth (p<0.05). Interestingly, all cloned calves weighed <15kg (n=5) or >35kg (n=9) at birth have been dead within 175 days from the date of birth. The causes of death in the cloned calves were premature birth (n=2, 10.0%), abnormal function of lung and liver (n=2, 10.0%), abnormal function of lung (n=4, 20.0%), malformation (n=4, 20.0%), unknown (n=4, 20.0%), and sudden death syndrome (n=4, 20.0%), respectively. Our findings suggest that normal birth weight is one of the most important factors to survive more than 6 months in cloned calves.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.4
• /
• pp.415-425
• /
• 2001

Background : The correlation between the high resolution computed tomography(HRCT) emphysema score and the physiologic parameters including resting and exercise pulmonary function test was investigated in 14 patients($60.6{\pm}10.3$ years) with pulmonary emphysema. Methods : The patients underwent a HRCT, a resting pulmonary function test, and incremental exercise testing(cycle ergometer, 10 W/min). Computed tomography scans were obtained on a GE highlight at 10 mm intervals using 10 mm collimation, from the apex to the base after a full inspiration. The emphysema scores were determined by a CT program 'Density mask' outlining the areas with attenuation values less than -900 HU, indicating the emphysema areas, and providing an overall percentage of lung involvement by emphysema. Results : Among the resting PFT parameters, only the diffusing capacity(r=-0.75) and $PaO_2$ (r=-0.66) correlated with the emphysema score(p<0.05). Among the exercise test parameters, the emphysema score correlated significantly with the maximum power(r=-0.74), maximum oxygen consumption(r=-0.68), anaerobic threshold(V-slope method: r=-0.69), maximal $O_2$-pulse(r=-0.73), and the physiologic dead space ratio at the maximum workload(r=-0.80)(p<0.01). Conclusion: We could find that exercise testing parameters showed a much better correlation with the HRCT emphysema score, which is known to have a good correlation with the pathologic severity than the resting PIT parameters. Therefore it is suggested that exercise testing is superior to resting PIT for estimating in the estimation of the physiologic disturbance in emphysema patients.