• Tuberculosis and Respiratory Diseases
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• 제58권2호
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• pp.135-141
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• 2005

배경 및 목적 : Multidrug Resistance-1 (MDR1) 유전자는 다약제내성에 관여하는 P-glycoprotein을 암호화한다. MDR1 유전자의 다형성은 P-glycoprotein의 발현과 기능의 차이를 일으켜 항암화학요법 반응에 영향을 미칠 수 있을 것이다. 저자들은 소세포폐암 환자에서 MDR1 유전자의 다형성과 일배체형에 따른 항암화학요법에 대한 반응을 조사하였다. 대상 및 방법 : 경북대학병원에서 병리적으로 소세포폐암으로 진단받고 etoposide-cisplatin 항암화학요법을 받은 54명을 대상으로 하였다. 전혈 5cc에서 DNA를 추출하고 PCR-RFLP법을 통해 MDR1 유전자 엑손 21의 2677G>T 다형성과, 엑손 26의 3435C>T 다형성을 조사하고 다형성과 일배체형에 따른 항암화학요법의 반응을 조사하였다. 결 과 : 2677G>T 유전자형에 따른 항암화학요법의 반응은 유의한 차이가 없었다. 3435 CC 유전자형은 3435 CT+TT 형에 비해 치료 반응율이 유의하게 높았다 (P = 0.025). 유전자형 분석 결과와 일치되게 2677G/3435C 일배체형은 다른 일배체형에 비해 치료반응을 보이는 경우가 유의하게 많았다 (P = 0.015). 결 론 : 소세포폐암에서 MDR1 유전자의 2677G>T와 3435C>T 다형성 및 이들 다형성의 일배체형은 etoposide-cisplatin 항암화학요법의 반응을 예측할 수 있는 지표로 사용될 수 있을 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.282-288
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• 2016

Background: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. Methods: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on $L{\ddot{o}wenstein$-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. Results: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). Conclusion: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.

• Tuberculosis and Respiratory Diseases
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• 제75권2호
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• pp.59-66
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• 2013

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

• Tuberculosis and Respiratory Diseases
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• 제40권4호
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• pp.404-409
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• 1993

연구배경 : 많은 재치료실패 환자들이 국립공주결핵병원에 입원해 있다. 그렇지만 이들에 대한 만족할만한 치료법이 없는 것이 현 실정이다. 이들에 대한 더 많은 관심과 적극적 대책이 필요하겠다. 방법 : 1992년 4월부터 1993년 2월까지 국립공주결핵병원에 입원하였던 재치료실패 환자 50명에 대하여 성별 및 연령별 분포, 질병기간, 항결핵제의 과거력, 약제내성, 병변의 크기, 조기중단 및 불규칙 복용의 이유 그리고 학력을 조사하였다. 결과: 1) 남녀의 비는 3:2였고 연령분포는 21~40세가 62%를 차지했다. 2) 28명(56%)이 10년이상의 질병기간을 가지고 있었다. 3) 모든 환자가 대부분의 항결핵제를 사용하였던 경험이 있었다. 4) RMP에 대한 내성은 96%에서, INH는 83%에서 나타났고 그밖의 항결핵제에 대한 내성은 6~67%에서 나타났다. 5) 48명(96%)이 중증으로 나타났다. 6) 초치료시는 28명(56%), 재치료시는 21명(42%)이 조기중단 및 불규칙 복용을 하였던 경험이 있었는데 그 이유는 초치료시는 '증상이 없어서'가 21명(75%) 이었고 재치료시는 '증상이 없어서'가 6명(29%), '생활이 바빠서'가 6명(29%) 그리고 '경제적 이유'가 3명(14%) 이었다. 7) 27(54%)이 고졸이상의 학력소유자이었다. 결론 : 치료실패를 방지하기 위하여 환자관리에 더 많은 노력이 필요하며 전염방지와 적절한 치료를 위하여 재치료실패 환자들에 대한 더 많은 지원과 입원치료가 필요하겠다.

• Tuberculosis and Respiratory Diseases
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• 제43권6호
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• pp.862-870
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• 1996

Background : Multidrug-resistant tuberculosis(MDR-Tb) has been increased not only in Asia but also in Western society, which may cause public health problems and reduce the efficacy of treatment of tuberculosis. In Western society HIV infection is believed to do a central role in increasing incidence of MDR tuberculosis, but MDR-Tb in Korea may be somewhat different about clinical features, underlying disorders, and prognosis. Goble et al reponed that overall treatment failure rate in MDR-Tb including resistance to isoniazid(INH) and rifampin (RFP) was 44 %. The aim of this study is to find the treatment result in Korea and the factors determining the prognosis. Methods: A retrospective study of pulmonary tuberculosis cultured M. tuberculosis from sputum or bronchial washing fluid between 1986 through 1992 was conducted in the Seoul Paik Hospital, Inje University. We reviewed clinical courses of 141 patients, who had a tuberculosis with resistance to 2 or more drugs including isoniazid(INH) and rifampin(RFP). One hundred and 4 patients of 141 patients had completed treatment and followed up for more than one year. Results: Of 104 (mean age $43.6{\pm}16.7$, M: F=63 : 41) patients with sufficient follow-up data, 73(84.6%) patients responded which is defined as negative Sputum cultures for at least 3 consecutive months. Seven patients(6.7%) had a failure in negative conversion and 9(8.7%) of the patients who initially responded relapsed. Overall treatment failure rate was 15.4%, Patients who were treated for less than 12 months had a higher relapse rate(12.3%) than 18 months(4.9%). And there was a statistically significant correlation between the relapse rate and the number of drugs to which isolates wera resistant(p<0.05). Conclusion : The treatment failure rate of MDR-Tb in Korea was lower than previous studies in western Country and the major determining factor of prognosis was the number of resistant drugs to M. tuberculosis at drug sensitivity test. For reducing the relapse rate, we recommend more than 12 months of treatment for MDR tuberculosis.

• Tuberculosis and Respiratory Diseases
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• 제64권3호
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• pp.187-193
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• 2008

연구배경: 다제내성결핵과 광범위내성결핵은 전세계적으로 결핵 치료에 큰 위협으로 등장하고 있지만 이에 대한 국내의 정확한 실태 및 추이는 잘 알려져 있지 않다. 일개 결핵병원에서 다제내성결핵과 광범위내성결핵의 빈도 및 추이를 살펴봄으로써 국내 실태를 간접적으로 파악하고자 하였다. 방법: 2001년부터 2005년 사이에 국립마산병원에 입원하여 배양양성 결핵으로 진단된 환자를 대상으로 약제 감수성검사 결과와 의무기록을 후향적으로 분석하였다. 결과: 2001년부터 2005년 사이에, 다제내성결핵은 신환자에서 9.2%, 13.8%, 16.9%, 23%, 27.0%로 의미있게 증가하였고(p<0.001 for trend) 재치료환자에서 9.1%, 15.7%, 17.3%, 19.9%, 19.1%로 의미있게 증가하였다 (p=0.002 for trend). 광범위내성결핵은 신환자에서 0%, 2.3%, 3.1%, 2.5%, 6.3%로 의미있게 증가하였고(p=0.005 for trend) 재치료환자에서 9.1%, 15.7%, 17.3%, 19.9%, 19.1%로 의미있게 증가하였다(p<0.001 for trend). 결론: 다제내성결핵과 광범위내성결핵은 신환자와 재치료환자 모두에서 증가하는 추이를 보였다. 국내의 정확한 실태 파악을 위하여 공공 및 민간의료기관을 포괄하는 통합적인 약제내성실태 조사가 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Tuberculosis and Respiratory Diseases
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• 제46권5호
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• pp.628-635
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• 1999

연구배경 : 만성 폐쇄성 폐질환을 대변하는 폐기종에서 주요 기능적 장애는 호기의 장애이며, 최대 호기류량은 기도의 크기, 폐의 탄력반동압 그리고 기도의 함몰성에 의해 결정된다. 기도의 항몰성은 폐기종에서 기류를 제한하는 하나의 기전으로 작용하지만, 폐용적과 폐의 과팽창을 유지하는 기전으로 작용하여 가스교환을 증진시킨다는 주장도 있다. 따라서 폐기종에서 기관이 호흡에 미치는 생리학적 역할이 무엇인지를 알아보고자 본 연구를 수행하였다. 방 법 : 1997년 1월 1일부터 8월 31일까지 보라매병원 호흡기내과를 방문하여 단순 흉부방사선검사, 체간용적기록계(body plethysmography)를 포함하는 폐기능검사 및 HRCT를 통해 폐기종으로 진단된 20명을 대상으로 하였다. HRCT에서 대동맥궁의 정상부위에서 기관의 단면적을 호흡주기에 따라 측정하고 이를 체표면적으로 보정한 값과 동맥혈의 이산화탄소분압 및 산소분압, 기도저항, 폐유순도 등 폐기능지표와의 상관 관계를 분석하였다. 결 과 : 폐기종에서 기관의 단면적은 호기시 동맥혈의 이산화탄소분압(r=-0.61, p<0.05) 및 산소분압(r=0.6, p<0.05) 그리고 매분환기량(r=0.73, p<0.05)과 유의한 상관관계가 있었지만, 흡기시에는 상관관계가 없었다(이산화탄소분압과는 r=-0.22, p>0.05, 산소분압과는 r=0.26, p>0.05, 매분환기량과는 r=0.44, p>0.05). 매분환기량은 상시호흡량(tidal volume)과는 r=0.45(p<0.05)로 유의한 상관관계가 있었지만, 호흡수와는 r=-0.31(p>0.05)로 상관관계가 없었다. 폐기종에서 기관의 단면적은 호흡주기와 상관없이 $FEV_1$ FVC, $FEV_1$/FEC, 최대 호기류량, 잔기용적, 폐확산능, 기도저항, 폐유순도 등의 다른 폐기능지표와는 상관관계가 없었다. 결 론 : 폐기종에서 호기시 기관의 단면적은 주로 가스 교환(gas exchange)의 지표들과 유의한 상관관계가 있었지만, 폐용적이나 폐의 과팽창을 시사하는 지표와는 상관관계가 없었다. 따라서 폐기종에서는 호기시 동일 압력점의 개념에 의해 발생하는 기도압박으로 기관의 단면적이 감소하고 이러한 현상이 기류를 제한하는 하나의 기전으로 작용하는 것이지 폐용적이나 폐의 과팽창을 유지시켜 가스교환을 증진시키는 것은 아니라고 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제73권1호
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• pp.38-47
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• 2012

Background: The prevalence rate of pulmonary tuberculosis (PTB) is steadily decreasing in South Korea. However, PTB is a disease with relatively high mortality and morbidity rates throughout Korea. Although there are many studies and statistics about the risk factors of PTB mortality in many countries, there are only a limited number of domestic papers on this topic. The aim of this study is to determine predictive factors for mortality among in-hospital patients associated with PTB. Methods: From December 2006 to January 2011, we reviewed medical records of 2,122 adult patients diagnosed with tuberculosis at a single tertiary hospital in a suburban area. In this study period, 960 patients were diagnosed with PTB by positive Acid fast bacilli smear and/or mycobacterial culture of the respiratory specimen. We compared the groups of patients deceased and patients discharged alive with PTB. The number of dead patients was 82 (47 males, 35 females). Results: Mortality was significantly associated with increased values of white blood cells (WBC), blood urine nitrogen (BUN), creatinine, C-reactive protein (CRP), numbers of involved lung field, and length of hospitalization. Also, it was associated with the decreased values of hemoglobin, lymphocyte, sodium, albumin, and cholesterol. Furthermore, admission through the emergency department, initial intensive care unit admission, and drug resistant PTB affected mortality in PTB patients. Independent predictors associated with PTB mortality are BUN, initial intensive care unit care, and admission during treatment of tuberculosis. Conclusion: In our study, mortality of pulmonary tuberculosis was related with parameters associated with nutritional status, disease severity at the time of admission, and drug resistance.