F-28 특발성 폐섬유화증에서 발생하는 폐암의 누적 발생률, 예측인자, 임상양상

유홍석,정병호,정명진,이경수,김호중,권오정,정만표 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.0

배경: 특발성 폐섬유화증에서 일반 인구에 비하여 폐암의 유병률이 높고, 그 예후 또한 나쁘다는 사실은 과거 연구를 통하여 알려져 있다. 하지만 폐암의 발생률과 폐암 발생을 예측할 수 있는 인자에 대해서는 아직 그 연구가 부족한 실정이다. 방법: 1998년부터 2013년까지 삼성서울병원에서 특발성 폐섬유화증으로 진단된 환자 중 진단 시 폐암의 증거가 없었던 환자들을 대상으로 후향적 분석을 시행하였다. 누적 발생률은 Kaplan-Meier 방법을 사용하여 추정하였고, 폐암 발생의 예측 인자는 Cox 비례 위험 모형을 통하여 분석하였다. 결과: 연구 기간 동안 특발성 폐섬유화증으로 진단된 환자 중 진단 시 폐암의 증거가 없었던 환자는 총 938명이었다. 평균 나이는 65.6세였고, 744명 (79.3%)이 남자였다. 682명 (72.7%)이 현재 혹은 과거 흡연자였으며, 진단 시 평균 노력성 폐활량 (FVC)은 83.0%였다. 추적 관찰 기간의 중앙값은 3.7년이었다. 938명의 환자 중 135 (14.4%)명에서 추적 관찰 중 폐암이 발생하였다. 1년, 3년, 5년, 10년 누적 발생률은 각각 1.1%, 8.7%, 15.9%, 31.1%였다. 폐암 발생과 유의한 연관을 보인 인자는 남자, 특발성 폐섬유화증 진단 시 흡연자, 연간 FVC 감소율이 10% 이상인 환자였다. 폐암의 병변은 주로 섬유화 주위 혹은 섬유화 내에 위치하였으며, 편평상피세포암이 가장 흔하였다. 결론: 폐암은 특발성 폐섬유화증에서 흔히 발생하며, 남자, 특발성 폐섬유화증 진단 시 흡연, 급격한 FVC 감소가 폐암 발생과 연관이 있었다.

F-31 The prognosis of lung cancer in patient with idiopathic pulmonary fibrosis according to treatment modality

( Songyi Han ),( Youlim Kim ),( Yeonjoo Lee ),( Jong Sung Park ),( Young-jae Cho ),( Ho Il Yoon ),( Jae Ho Lee ),( Choon-taek Lee ),( Sang Hoon Lee ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Background: There were evidences that IPF is one of the important risk factor of lung cancer (LC) and as time passes after the diagnosis of IPF. In this study, we aim to find out what treatments are associated with a better prognosis for LC patients with IPF. Method: From 2003 to 2016, a total of 299 patients with both IPF and LC were searched by the diagnostic name in the Seoul National University Bundang hospital. 168 patients were included in the analysis except for other form of ILD, infection (n=13), other malignancy (n=11), and missing data (n=102). Among the patients, 21 were conservative therapy, 66 were surgery, 69 were chemotherapy, and 6 were treated for radiation therapy as primary treatment. GAP score was calculated with gender, age, FVC, and DLCO as Ley et al. reported. Results: The average age was 69.9 years and the men were dominant (92.9%). The overall survival rate was high in surgery (p<0.001; HR, 0.144) and chemotherapy (p=0.046; HR, 0.487). Surgery (p=0.014; HR, 0.244) increased the survival rate in the lung cancer stage I, II, and IIIa, and chemotherapy (p<0.001; HR, 0.168) and surgery (p=0.003; HR, 0.033) improved the survival rate in the IIIb and IV, compared to the conservative care. The survival rate was improved by surgery (p<0.001; HR, 0.132) in GAP stage I and was increased by chemotherapy (p = 0.007; HR, 0.145) in stages II and III. Conclusion: Although the motality of IPF-associated LC is higher than lung cancer only, it seems to be effective for surgery or chemotherapy depending on the lung cancer or IPF stage.

P-135 The Value of 18F-FDG PET/CT in evaluating disease severity in idiopathic pulmonary fibrosis

윤희영,고의원,이석현,하세진,류진숙,김동순,송진우 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Objectives: Several biomarkers have been reported to be useful in assessing disease severity of idiopathic pulmonary fibrosis (IPF); however, the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG/PET-CT) is not well defined. The aim of study was to investigate the value of 18F-FDG PET/CT for assessing disease severity in IPF Methods: Clinical data were retrospectively reviewed in 89 IPF patients (mean age: 68.1 years, male: 94%) who performed 18F-FDG PET/CT for cancer evaluation at Asan Medical Center, Seoul. Standardized uptake value (SUV) was measured only in fibrotic area, and lesion-to-liver SUV ratio (SUVR) was also obtained. Correlation between 18F-FDG PET/CT parameters (SUV and SUVR) and clinical parameters including lung function, exercise capacity, and GAP index were analyzed. Results: Median follow-up period was 11.9 months and lung cancer was confirmed in 61 (69%) patients. SUV and SUVR were significantly correlated with forced vital capacity (r=-0.214, r=-0.275, respectively), diffusing capacity for carbon monoxide (r=-0.375, r=-0.373), distance (r=-0.297, r=-0.318) and the lowest oxygen saturation (r=-0.255, r=-0.339) during 6-minute walk test, and GAP index (r=0.343, r=0.321). SUV were also significantly correlated with decline in total lung capacity after 6 months (r=-0.501). SUVR was predictor for death (hazard ratio [HR]: 1.466; 95% confidential index: 1.009-2.131; p=0.045) on univariate analysis Conclusions: Our findings suggest that 18F-FDG PET/CT may be useful to assess disease severity in patients with IPF.

F-36 Upregulation of Potassium Voltage-Gated Channel Subfamily J Member 2 levels in the lungs of idiopathic pulmonary fibrosis

( Chang An Jung ),( Jong-uk Lee ),( Hun Soo Chang ),( Jong-sook Park ),( Soo-taek Uh ),( Young Hoon Kim ),( Choon-sik Park ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. KCNJ2 plays critical roles in maintaining the resting potential and controlling excitability of the cells. KCNJ2 has been revealed to involve in the development of cardiac fibrosis. However, the functional importance of KCNJ2 has not been evaluated in IPF. KCNJ2 mRNA expression was measured using real time PCR. The protein concentration was measured by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluids obtained from normal controls (n=30) and from patients with idiopathic pulmonary fibrosis (n=84), non-specific interstitial pneumonia (n=10), hypersensitivity pneumonitis (n=10), and sarcoidosis (n=10). KCNJ2 mRNA levels were significantly higher in IPF-fibroblasts(n=14) than those in controls(n=10). KCNJ2 protein levels were significantly higher in the IPF patients than those in the NC [0.039(0.00-0.107ng/ug) vs. 1.299(0.228-3.975ng/ug), p=1.168E-9], those in the NSIP [0.042(0.006-1.262ng/ug), p=0.022], those in the HP [0.777(0.000-0.539ng/ug), p=0.006] and those in the sarcoidosis patients [0.026(0.011-0.099ng/ug), p=0.0001]. ROC curve showed a clear difference between the IPF patients and NC (AUC=0.875). A cut-off value (0.1771ng/ug) possessed 82.5% accuracy with 90.0% specificity and 79.8% sensitivity between the IPF patients and NC. KCNJ2 may be associated with the development of IPF. Furthermore, the KCNJ2 in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases.

Efficacy of lower dose Pirfenidone for idiopathic pulmonary fibrosis in real practice of Korea

( Hyeontaek Hwang ),( Jung-kyu Lee ),( Sun Mi Choi ),( Jun Yeun Cho ),( Yeon Joo Lee ),( Young-jae Cho ),( Ho Il Yoon ),( Jae Ho Lee ),( Choon-taek Lee ),( Young Whan Kim ),( Jong Sun Park ) 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Introduction: Pirfenidone reduced the rate of disease progression in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the efficacy and adverse events of pirfenidone in real practice of Korea and whether the lower dose of pirfenidone is also effective in patients with IPF. Method: This study was a multi-center retrospective cohort study of patients with IPF involved 3 referral centers in Korea. Patients treated with pirfenidone between July 2012 and March 2018 were enrolled. Efficacy was analyzed according to the dose of pirfenidone using linear mixed effects model for annual rate of decline in forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). Results: A total of 338 patients were analyzed. The mean duration of treatment was 16.1±9.0 months. About 20% of the patients received pirfenidone as a standard dose (1800mg) for more than 6 months (standard dose group). However, 80% had pirfenidone below 1200mg (non-standard dose group). The annual decline of predicted FVC was -5.34% [95% CI -6.56, -4.12] per year before treatment with pirfenidone, but -2.89% [95% CI -3.64, -2.14] per year after treatment. The annual decline of FVC and DLCO was significantly attenuated after pirfenidone treatment (p<0.001), these effect was similar in both standard and non-standard dose groups. Conclusion: Pirfenidone reduced the rate of decline of FVC and DLCO in Korean IPF patients. This effect persists even after continual lower dose of pirfenidone.

Clinical features and prognosis of pleuroparenchymal fibroelastosis: a single center experience

( Jae Ha Lee ),( Eun Jin Chae ),( Joon Seon Song ),( Dong Soon Kim ),( Jin Woo Song ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Background: Pleuroparenchymal fibroelastosis (PPFE) is one of rare idiopathic interstitial pneumonias (IIP); however, clinical features and prognosis are not well defined. Methods: Patients (n=18), who were diagnosed by lung biopsy (surgical lung biopsy: 10, transbronchial lung biopsy: 8) from 2010 to 2017 at Asan medical center, were included and clinical data of them were retrospectively reviewed. Results: Median follow-up period was 12.5 months. Mean age was 62.7±9.9 years old, 67% were men and 55.6% were smokers. Cough (77.8%) and dyspnea (88.9%) were the most frequent presenting symptoms. About half of the subjects had a history of pulmonary infection (38.9%), chemotherapy (5.6%) and organ transplantation (5.6%). Most patients (66.7%) showed restrictive pattern on lung function test (mean FVC: 61.5±21.5% predicted, DLco: 57.6±18.6% predicted) and mild neutrophilia (mean: 10.1±13.8%) on bronchoalveolar larvage. Ten (55.6%) patients showed findings of other interstitial lung disease (ILD) in both lower lobes on chest CT scan images, and on lung biopsy, UIP pattern was found in 16.7% and OP pattern in 22.2%, additionally. Fourteen (77.8%) patients were treated with steroid±immunosuppresants, pneumothorax was developed in 38.9% and 27.8% died during follow-up (1-year survival rate: 81.5%, 5-year: 36.2%). Respiratory infection (40%) was the most common cause of death. Conclusion: Half of the subjects had a relevant exposure history and other ILD on chest CT, and prognosis was similar to non-IPF-IIPs.

Clinical significance of pleuroparenchymal fibroelastosis in patients with idiopathic pulmonary fibrosis

이송이,채은진,김동순,송진우 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.0

Background: Pleuroparenchymal fibroelastosis(PPFE) is a rare condition that consists of fibrosis involving the pleura and subpleural lung parenchyma. In some patients, other interstitial lung disease (usually usual interstitial pneumonia) is identified in the lower lobe. The aim of the study is to evaluate clinical significance of PPFE in patients with idiopathic pulmonary fibrosis (IPF). Methods: Clinical and radiologic data were retrospectively analyzed in 445 patients(biopsy proven cases, n=165) with IPF. Radiologic criteria of PPFE were defined as follows: 1) bilateral subpleural dense consolidation with or without pleural thickening in the upper lobes, 2) evidence of disease progression, 3) no evidence of identifiable etiologies, multiple lung or pleural calcification and unilateral lesion. Results: PPFE was identified in 28 patients (6.3%). The PPFE group showed lower body mass index (BMI, 21.2 vs. 24.4 kg/㎡, p<0.001), forced vital capacity (58.7 vs. 69.4 % predicted, p=0.003) and total lung capacity (62.7 vs. 69.7 % predicted, p=0.05), compared with the non-PPFE group. Pneumothorax (17.9% vs 3.6%, p<0.001) and pneumomediastinum (21.4% vs 4.6%, p <0.001) occurred more frequently in PPFE group. Median survival time was not different between two groups (32.0 [PPFE] vs. 37.0 months[non-PPFE], p=0.155), but the PPFE group showed worse 1 year survival than non-PPFE group (75.0 vs. 92.1%, p=0.002 ). Conclusions: IPF with PPFE showed lower BMI and lung function, more frequent pneumothorax and pneumomediastinum and poorer short-term prognosis, compared with those without PPFE.

P-134 Incidence of radiation pneumonitis in lung cancer patients with idiopathic pulmonary fibrosis

김재경,( Jinwoo Lee ),( Young Sik Park ),( Chang-hoon Lee ),( Sang-min Lee ),( Jae-joon Yim ),( Chul-gyu Yoo ),( Young Whan Kim ),( Sung Koo Han ),( Sun Mi Choi ) 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Background: Idiopathic pulmonary fibrosis (IPF) is well known to affect the prognosis of lung cancer. The goal of this study was to evaluate the incidence of radiation pneumonitis after radiotherapy in lung cancer patients with IPF and compare it to those without IPF. Methods: We retrospectively reviewed medical records of patients who had received radiation therapy on lung cancer in 2 tertiary university hospitals from 2004 to 2014. We excluded patients treated with palliative radiotherapy or SABR (Stereotactic ablative radiotherapy). Results: During the period, total 1445 patients underwent radiation therapy for lung cancer. Among them, 53 patients had IPF when they had been diagnosed with lung cancer. We selected 2 matched controls (matched by lung cancer stage, histopathology, and sex) for each patient with IPF. Baseline characteristics, ECOG, middle or lower location of lung cancer, stage, pathology, total radiation dose were not different significantly between two groups. Radiation pneumonitis developed in 30/53 (60%) in IPF patients and 54/94 (57.4%) in patients without IPF (p=0.767). Among those with radiation pneumonitis, more than grade 2 radiation pneumonitis was more prevalent in IPF patients (48.3%) than in non-IPF patients (9.6%, p-value 0.001). Conclusion: The incidence of radiation pneumonitis in lung cancer patients with IPF was similar to that in those without IPF. On the other hands, more than grade 2 radiation pneumonitis treated with steroid or oxygen was more prevalent in lung cancer patients with IPF than those without IPF.