A Comprehensive Analysis for Clinical Outcomes in Patients with Cancer Admitting Intensive Care Unit

( Yoonki Hong ),( Woo Jin Kim ),( Young Soon Yoon ),( Yunjeong Jeong ),( Yunseong Kang ),( Ju-hee Park ),( Jinkyeong Park ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Objective Until recently, studies on long- term outcomes of critically ill patients with cancer have been mainly restricted to specific subgroups of patients. This study aims to evaluate the long-term clinical outcomes of patients who received intensive care unit treatment for 5 years using the Korean nationwide data. Method All patients >18 year of age having ICU admission were enrolled from the claims data from the Health insurance review and assessment service (HIRA) from Jan 2008 to Dec 2010. Enrolled patients were followed up to Dec 2015. We analyzed clinical outcomes including mortality admitting to ICU. Critically ill patients categorized into four subgroups; patients without cancer, with solid cancer except lung, with lung cancer and with hematologic malignancies. Result Of all critically ill patients (n= 323,765) admitted to the intensive care unit, the proportion of cancer patients continued to increase from 21.5% in 2008 to 27.8% in 2010. Critically ill patients with cancer showed higher ICU mortality (18.6%) than patients without cancer (13.2%, P-value <0.001). There was no difference in ICU mortality at day 28 among patients without cancer (14.5%) and with cancer which was not lung cancer or hematologic malignancies (14.3%, P-value = 0.28). Hazard rates for the ICU mortality at 5 years were 1.90 (95% confidence interval 1.87-1.94) in lung cancer, 1.44 (95% CI, 1.43-1.46) in other solid cancers, and 3.05 (95% CI, 2.95-3.16) in hematologic malignancies compared to patients without cancer. Conclusion This study show that in the short term, the outcomes of critically ill patients having cancer were not significantly different from that of general patients, except for lung cancer and hematologic malignancies. However, long-term survival rate of cancer patients was significantly worse than that of general critical patients.

Influence of Environmental Exposures on Patients with Chronic Obstructive Pulmonary Disease in Korea

Hong, Yoonki,Lim, Myoung Nam,Kim, Woo Jin,Rhee, Chin Kook,Yoo, Kwang Ha,Lee, Ji-Hyun,Yoon, Ho Il,Kim, Tae-Hyung,Lee, Jin Hwa,Lim, Seong Yong,Lee, Sang Do,Oh, Yeon-Mok The Korean Academy of Tuberculosis and Respiratory 2014 Tuberculosis and Respiratory Diseases Vol.76 No.5

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. Methods: The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. Results: Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. Conclusion: COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

Poor interpretation of pulmonary function tests in patients with concomitant decreases in FEV₁ and FVC

HONG, Yoonki,RA, Seung W.,SHIM, Tae S.,LIM, Chae-Man,KOH, Younsuck,LEE, Sang D.,KIM, Woo S.,KIM, Dong-Soon,KIM, Won D.,OH, Yeon-Mok Blackwell Publishing Asia 2008 Respirology Vol.13 No.4

<P>Background and objective: </P><P>A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV<SUB>1</SUB> and FVC.</P><P>Methods: </P><P>A retrospective study was conducted of 681 patients with normal FEV<SUB>1</SUB>/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy.</P><P>Results: </P><P>The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; <I>P</I> < 0.0001).</P><P>Conclusions: </P><P>The weak agreement between the clinical diagnosis and the PFT interpretation in patients showing concomitant decreases in FEV<SUB>1</SUB> and FVC suggests that other clinical findings should be assessed in addition to PFT.</P>

Implications of Emphysema and Lung Function for the Development of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease

Hong, Yoonki,Lee, Jae Seung,Yoo, Kwang Ha,Lee, Ji-Hyun,Kim, Woo Jin,Lim, Seong Yong,Rhee, Chin Kook,Lee, Sang-Do,Oh, Yeon-Mok The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.2

Background: Chronic obstructive pulmonary disease (COPD) is sometimes complicated with pneumonia, but little is known about the risk factors that promote the development of pneumonia in COPD. These risk factors were evaluated in the present study. Methods: The data of 324 patients with COPD from a prospective multi-center observational cohort with obstructive lung disease were evaluated retrospectively. To identify risk factors for the development of pneumonia in COPD, the clinical and radiological data at enrollment and the time to the first episode of pneumonia were analyzed by Cox proportional hazard analysis. Results: The median follow-up time was 1,099 days and 28 patients (8.6%) developed pneumonia. The Cox analysis showed that post-bronchodilator forced expiratory volume in one second ($FEV_1$, % of predicted) and the computed tomography (CT) emphysema extent (inspiratory V950) were independent risk factors for the development of pneumonia (post-bronchodilator $FEV_1$: hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.94-1.00; p=0.048 and inspiratory V950: HR, 1.04; 95% CI, 1.01-1.07; p=0.01). Conclusion: Emphysema severity measured by CT and post-bronchodilator $FEV_1$ are important risk factors for the development of pneumonia in COPD.

Identification of Alternative Splicing and Fusion Transcripts in Non-Small Cell Lung Cancer by RNA Sequencing

Hong, Yoonki,Kim, Woo Jin,Bang, Chi Young,Lee, Jae Cheol,Oh, Yeon-Mok The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.2

Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

Contributors of the Severity of Airflow Limitation in COPD Patients

( Yoonki Hong ),( Eun Jin Chae ),( Joon Beom Seo ),( Ji-Hyun Lee ),( Eun-Kyung Kim ),( Young Kyung Lee ),( Tae-Hyung Kim ),( Woo Jin Kim ),( Jin Hwa Lee ),( Sang-Min Lee ),( Sangyeub Lee ),( Seong Yon 대한결핵 및 호흡기학회 2012 Tuberculosis and Respiratory Diseases Vol.72 No.1

Although airway obstruction in chronic obstructive pulmonary disease (COPD) is due to pathologic processes in both the airways and the lung parenchyma, the contribution of these processes, as well as other factors, have not yet been evaluated quantitatively. We therefore quantitatively evaluated the factors contributing to airflow limitation in patients with COPD. The 213 COPD patients were aged >45 years, had smoked >10 pack-years of cigarettes, and had a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. All patients were evaluated by medical interviews, physical examination, spirometry, bronchodilator reversibility tests, lung volume, and 6-minute walk tests. In addition, volumetric computed tomography (CT) was performed to evaluate airway wall thickness, emphysema severity, and mean lung density ratio at full expiration and inspiration. Multiple linear regression analysis was performed to identify the variables independently associated with FEV1 - the index of the severity of airflow limitation. Multiple linear regression analysis showed that CT measurements of mean lung density ratio (standardized coefficient β=?0.46; p<0.001), emphysema severity (volume fraction of the lung less than ?950 HU at full inspiration; β=?0.24; p<0.001), and airway wall thickness (mean wall area %; β=?0.19, p=0.001), as well as current smoking status (β=?0.14; p=0.009) were independent contributors to FEV1. Mean lung density ratio, emphysema severity, and airway wall thickness evaluated by volumetric CT and smoking status could independently contribute to the severity of airflow limitation in patients with COPD.

A Comprehensive Analysis of 5-Year Outcomes in Patients with Cancer Admitted to Intensive Care Units

( Yoonki Hong ),( Woo Jin Kim ),( Ji Young Hong ),( Yun-jeong Jeong ),( Jinkyeong Park ) 대한결핵 및 호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2

Background: The aim of this study was to evaluate the long-term (5-year) clinical outcomes of patients who received intensive care unit (ICU) treatment using Korean nationwide data. Methods: All patients aged >18 years with ICU admission according to Korean claims data from January 2008 to December 2010 were enrolled. These enrolled patients were followed up until December 2015. The primary outcome was ICU mortality. Results: Among all critically ill patients admitted to the ICU (n=323,765), patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p<0.001). However, there was no significant difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer (lung cancer or hematologic malignancies) (14.3%). Compared to patients without cancer, hazard ratios of those with cancer for ICU mortality at 5 years were: 1.90 (1.87-1.94) for lung cancer; 1.44 (1.43-1.46) for other solid cancers; and 3.05 (2.95-3.16) for hematologic malignancies. Conclusion: This study showed that the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients. However, short term outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for those with lung cancer or hematologic malignancies.

Identification of lung cancer specific differentially methylated regions using genome-wide DNA methylation

Yoonki Hong,Seok-Ho Hong,Yeon-Mok Oh,Seung-Ho Shin,Sun Shim Choi,Woo Jin Kim 대한독성 유전단백체 학회 2018 Molecular & cellular toxicology Vol.14 No.3

Backgrounds: Many molecular biomarkers have been suggested for the diagnosis, prognosis, and treatment response of lung cancer, but their clinical availability remains limited. DNA methylation is one such promising biomarker because it is stable and easily detected. Methods: We conducted an epigenome-wide analysis using methyl binding domain (MBD) sequencing in tissues of lung cancer patients. Tumor and normal tissues were obtained from two patients who underwent surgery for non-small cell lung cancer. Results: HOXA5, HOXA9, and other related genes were associated with the CGI-located DMRs in Patient 1, whereas the SSTR5 gene was found to be associated with the CGI-located DMRs in Patient 2. Interestingly, these DMR genes were mapped in the physical interaction networks that included previously known nonsmall cell lung cancer genes. Conclusion: This genome-wide DNA methylation study showed an association between newly identified DMRs in CpG island promoter regions and previously known target genes for lung cancer.

Levels of vitamin D-associated cytokines distinguish between active and latent tuberculosis following a tuberculosis outbreak

( Yoonki Hong ),( Myung Goo Lee ),( Chang Youl Lee ),( Youlim Kim ),( Jeongwon Heo ),( Seon-sook Han ),( Seung-joon Lee ),( Woo Jin Kim ),( Ji Young Hong ) 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Background: Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). Methods: In total, 26 healthy controls and 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma vitamin D, IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay. Results: Vitamin D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (vitamin D: 16.64 ng/mL vs. 21.6 ng/mL, P=0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P=0.013). Plasma vitamin D levels correlated with the plasma levels of IL-15 and IL-1β. In addition, the plasma vitamin D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964. Conclusions: Together, our preliminary data suggest that the levels of the vitamin D-related cytokines IL-15 and IL-32 may be used to create a biomarker distinguishing between active TB and LTBI.

A Comprehensive Analysis of 5-Year Outcomes in Patients with Cancer Admitted to Intensive Care Units

Yoonki Hong,Kim Woo Jin,Hong Ji Young,Jeong Yun-jeong,Park Jinkyeong 대한결핵및호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2

Background: The aim of this study was to evaluate the long-term (5-year) clinical outcomes of patients who received intensive care unit (ICU) treatment using Korean nationwide data.Methods: All patients aged >18 years with ICU admission according to Korean claims data from January 2008 to December 2010 were enrolled. These enrolled patients were followed up until December 2015. The primary outcome was ICU mortality.Results: Among all critically ill patients admitted to the ICU (n=323,765), patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p<0.001). However, there was no significant difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer (lung cancer or hematologic malignancies) (14.3%). Compared to patients without cancer, hazard ratios of those with cancer for ICU mortality at 5 years were: 1.90 (1.87–1.94) for lung cancer; 1.44 (1.43–1.46) for other solid cancers; and 3.05 (2.95–3.16) for hematologic malignancies.Conclusion: This study showed that the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients. However, short term outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for those with lung cancer or hematologic malignancies.