결핵 환자에서 면역학적 지표로서의 sIL-2R, IFN-$\gamma$, Neopterin에 관한 연구

류연주,유금혜,김수현,이종수,천선희,서주영,Ryu, Yon-Ju,Ryu, Kum-Hei,Kim, Su-Hyun,Lee, Jong-Soo,Cheon, Seon-Hee,Seoh, Ju-Young 대한결핵및호흡기학회 2002 Tuberculosis and Respiratory Diseases Vol.53 No.3

연구배경 :결핵은 세포 매개성 면역반응이 병태생리에 중요한 역할을 하는 감염성 질환이다. 결핵균 항원으로 T 림프구가 활성화되면 여러 종류의 cytokine을 분비하며 T 림프구의 분화와 증식, 대식세포의 활성화를 촉진한다. 본 연구에서는 결핵의 중증도, 숙주의 면역상태 및 예후를 반영하는 지표로서 활성화된 T 림프구에서 만들어지는 IL-2의 수용성 수용체인 sIL-2R와 IFN-$\gamma$를 측정하였고 활성화된 대식세포에서 분비되는 neopterin을 측정하여 임상적 유용성을 판정하고자 하였다. 대상 및 방법 :활동성 폐결핵 환자 39명, 결핵성 림프절염 환자 6명의 치료전과 정상 대조군 10명에서 혈청 sIL-2R, neopterin, IFN-$\gamma$를 측정하였고, 결핵성 흉막염 환자 22명에서 치료전 혈청과 흉막액에서 각각 sIL-2R, ADA, neopterin을 측정하였다. 폐결핵 환자 39명을 ATS guidelines에 따라 중증도를 분류하였고, 사망한 1명과 결핵요양소로 전원된 2명을 제외한 36명에서 초치료 2개월 후 혈청 sIL-2R, neopterin과 IFN-$\gamma$를 측정하였다. 결 과 : 1) sIL-2R과 IFN-$\gamma$는 결핵환자에서 대조군에 비하여 증가된 경향을 보였다(p>0.05). Neopterin은 대조군 $4949{\pm}1242.l$ pg/ml, 폐결핵 $29.67{\pm}2132.8$ pg/ml, 결핵성 림프절엽 $3013{\pm}1877.3$ pg/ml, 결핵성 흉막염이 $2035{\pm}1216.4$ pg/ml로 결핵환자에서 대조군에 비하여 감소되는 경향을 보였으며, 폐결핵군과 결핵성 흉막염군에서는 통계적으로 유의하게 감소되어 있었다(p<0.05). 2) 폐결핵의 중증도가 심할수록 sIL-2R와 IFN-$\gamma$는 증가하였고, neopterin은 감소하였다(p<0.01). 3) 폐결핵 환자 36명에서 치료 후 측정한 sIL-2R는 $1071{\pm}l139.4$ U/ml에서 $1023{\pm}1920.9$ U/ml로(p>0.05), IFN-$\gamma$는 $41{\pm}52.8$ pg/ml에서 $22{\pm}23.9$ pg/ml로 각각 감소하였고 (p<0.05), neopterin은 $3158{\pm}2272.6$ pg/ml에서 $3737{\pm}2307.5$ pg/ml로 증가하였다(p>0.05). 이러한 결과는 경증군과 중등증군에 비해 중증군에서 현저한 변화를 보였고 임상적 경과와 상관성을 보였다. 4) 결핵성 흉막염 환자 22명에서 sIL-2R와 ADA는 혈청에 비하여 흉막액에서 유의하게 높은 값을 보였으나(p<0.01), neopterin은 차이가 없었다(p>0.05). 결 론 : 이상의 결과를 바탕으로 특히 중증군에서 치료 후에 sIL-2R, IFN-$\gamma$와 neopterin을 추적 관찰하면 숙주의 면역반응상태, 임상적 중증도 및 치료 반응성을 예측하는데 도움이 될 것으로 생각된다. 또한 결핵성 흉막염 환자에서는 국소적인 변역반웅의 활성화로 흉막액내의 면역학적 지표의 측정이 혈청 검사보다 특이적이며, 흉막액의 sIL-2R의 측정이 결핵성 흉막염의 진단에 유용할 것으로 생각된다. Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

Progressive Multiple Cystic Changes in Both Lungs in a Patient Treated with Gefitinib for Lung Adenocarcinoma with Multiple Lung Metastases

류연주,천은미,이순남,심성신 대한영상의학회 2014 Korean Journal of Radiology Vol.15 No.2

Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not beenreported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

Prevalence of Depression and Anxiety in Outpatients with Chronic Airway Lung Disease

류연주,천은미,이진화,장중현 대한내과학회 2010 The Korean Journal of Internal Medicine Vol.25 No.1

Background/Aims: Patients with chronic airway lung diseases often experience depression and anxiety, but little information is available regarding Koreans with these conditions. We thus assessed depression and anxiety in Korean patients with chronic airway lung diseases. Methods: The degree of depression and anxiety in 84 outpatients with chronic obstructive pulmonary disease (COPD), 37 with asthma, 33 with bronchiectasis, and 73 healthy controls were evaluated by the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Results: The patients with COPD and bronchiectasis had higher BDI scores and were more likely than controls to experience depression ([COPD, 17; range, 0 to 42; prevalence, 55%], [bronchiectasis, 16; range, 3 to 51;prevalence, 55%], [controls, 13; range, 0 to 31; prevalence, 30%], p < 0.05). The state-anxiety scores of the patients were higher than those of the controls, but only the bronchiectasis group demonstrated a higher frequency of state-anxiety compared with the controls (39 vs. 16%, patients vs. controls, p = 0.015). Among all patients, 22% presented with concomitant depression and state-anxiety, and 25% demonstrated depression and trait-anxiety. Depression was positively correlated with both state-anxiety (r = 0.644) and trait-anxiety (r = 0.597, p < 0.0001). Irrespective of individual diagnosis, post-bronchodilator FEV1 (odds ratio [OR], 0.972; p = 0.027)and smoking history (OR, 3.894; p = 0.018) were independent risk factors for depression in patients with chronic airway lung diseases. Conclusions: Chronic airway lung diseases are associated with depression and/or anxiety, particularly in those with a higher airflow limitation and/or history of smoking. (Korean J Intern Med 2010;25:51-57)

Diagnosis of Pulmonary Tuberculosis: Recent Advances and Diagnostic Algorithms

류연주 대한결핵및호흡기학회 2015 Tuberculosis and Respiratory Diseases Vol.78 No.2

Pulmonary tuberculosis (TB) persists as a great public health problem in Korea. Increases in the overall age of the population and the rise of drug-resistant TB have reinforced the need for rapid diagnostic improvements and new modalities to detect TB and drug-resistant TB, as well as to improve TB control. Standard guidelines and recent advances for diagnosing pulmonary TB are summarized in this article. An early and accurate diagnosis of pulmonary TB should be established using chest X-ray, sputum microscopy, culture in both liquid and solid media, and nucleic acid amplification. Chest computed tomography, histopathological examination of biopsy samples, and new molecular diagnostic tests can be used for earlier and improved diagnoses, especially in patients with smear-negative pulmonary TB or clinically-diagnosed TB and drug-resistant TB.

양성 기도협착질환에서 실리콘 기도스텐트의 임상경험 -Dumon 스텐트와 Natural 스텐트의 비교-

류연주,서수원,김진국,김호중,유창민,최재철,권용수 대한결핵및호흡기학회 2005 Tuberculosis and Respiratory Diseases Vol.59 No.1

Background : The clinical results of a Natural stent in patients with a benign tracheobronchial stenosis were examined by comparing the clinical outcomes and complications of those patients who underwent Dumon and Natural stenting in the management of benign airway stenosis. Methods : The medical records of 94 patients (39 Dumon and 55 Natural stent) with a benign tracheobronchial stenosis were reviewed and analyzed. Results : Post-tuberculous stenosis was the leading indication for airway stenting (74%), which was followed by post-intubation stenosis (21%). After intervention, the dyspnea had improved among those patients who underwent Dumon (90%) and Natural (86%) stenting. After stabilizing the dyspnea, the stent could be successfully removed in half of the patients who underwent both Dumon (54%) and Natural (49%) stenting. During the 42 month follow-up period, the complication rate was similar in those patients who underwent Dumon and Natural stenting: migration (46% vs 53%), granulation tissue formation (36% vs 49%), mucostasis (21% vs 16%) and restenosis (51% vs 36%). Conclusion : The clinical results of Natural airway stent was similar to those of Dumon stent in the management of benign tracheobronchial stenosis. (Tuberc Respir Dis 2005; 59: 62-68) 연구배경 : 양성 기도협착질환 환자에서 새로 개발된 Natural 기도스텐트의 임상결과를 Dumon 스텐트와 비교하였다. 방 법 : 양성 기도협착으로 스텐트를 삽입한 94명의 환자 (39 Dumon, 55 Natural)를 대상으로 임상증상, 시술 전 검사결과, 시술방법, 그리고 추적관찰시의 임상경과를 후향적으로 조사하였다. 결 과 : 원인질환으로 기관지결핵 후 기도협착 (74%)이 가장 많았고, 기관삽관 후 기관협착 (20명), 기관절개술 후 기관협착 (2명)등이 있었다. 스텐트를 삽입한 후, 전체 94명의 환자 중 82명 (87%)에서 주관적으로 호흡곤란이 개선되었고, Dumon 스텐트군 (35/39, 90%)과 Natural 스텐트군 (47/55, 86%) 사이의 차이는 없었다. 모두 48명 (51%)에서 중앙값 14개월 (범위 6-37개월)후에 스텐트를 성공적으로 제거할 수 있었고, Dumon 스텐트군 (54%, 16개월 후) 과 Natural 스텐트군 (49%, 12개월 후)간의 차이는 없었다. 스텐트 삽입 후 부작용은 스텐트의 위치 변동이 45명 (48%)에서, 육아종 과형성이 41명 (44%)에서, 점액저류에 의한 스텐트 내경 50% 이상의 감소가 17명 (18%)에서, 그리고 스텐트 삽입 전후부위의 협착이 40명 (43%)에서 발생하였다. Dumon 과 Natural 스텐트를 삽입한 환자들 사이에서 부작용의 분포의 차이는 없었다.

결핵 환자에서 면역학적 지표로서의 sIL-2R, IFN- γ, Neopterin에 관한 연구

류연주,유금혜,김수현,이종수,천선희,서주영 대한결핵 및 호흡기학회 2002 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.95 No.0

만성폐쇄성폐질환 환자에서 우울과 불안심리 평가

류연주,청은미,심윤수,이진화,문진욱,장중현 대한결핵 및 호흡기학회 2006 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.103 No.-

악성 흉수의 진단에서 혈청과 흉수의 CEA, NSE, CYFRA 21-1 측정의 유용성

류연주,이진화,천은미,장중현 대한결핵 및 호흡기학회 2003 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.97 No.0

구연 : 호흡기 ; 기관지반응성의 임상적 의의 및 메타콜린으로 유도된 천식발작시 폐기능 변화와의 관계

류연주,최영주,곽재진,장중현,천선희 대한내과학회 2001 대한내과학회 추계학술대회 Vol.61 No.-

60세 이상의 노인환자에서 수술전 검사로서 경흉부심장초음파검사는 필요한가

류연주,신길자 한국심초음파학회 2001 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.9 No.2