Young Whan Kim

Pusan National University, Busan, Busan, South Korea

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Publications (285)629.36 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: Low-dose chest computed tomography (LDCT) screening increased detection of airway nodules. Most nodules appear to be secretions, but pathological lesions may show similar findings. The National Comprehensive Cancer Network (NCCN) recommends repeating LDCT after 1 month and proceeding to bronchoscopy if the nodules persist. However, no reports exist about incidentally detected airway nodules. We investigated the significance of airway nodules detected by LDCT screening.We screened patients with incidental airway nodules detected by LDCT in the Seoul National University Hospital group. The characteristics of computed tomography, bronchoscopy, pathology and clinical findings were analysed.Among 53 036 individuals who underwent LDCT screening, 313 (0.6%) had airway nodules. Of these, 186 (59.4%) were followed-up with chest computed tomography and/or bronchoscopy. Seven (3.8%) cases had significant lesions, including leiomyoma (n=2), endobronchial tuberculosis (n=2), chronic inflammation (n=1), hamartoma (n=1) and benign granuloma (n=1). The remaining 179 lesions were transient, suggesting that they were secretions.The use of LDCT for lung cancer screening demonstrated the low incidence of airway lesions. Most lesions were transient secretions. True pathological lesions were rare, and no malignant lesion was found. The current recommendation of the NCCN guideline is a reasonable approach that can avoid unnecessary bronchoscopy.
    No preview · Article · Mar 2016 · European Respiratory Journal
  • [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: A low albumin-to-globulin ratio (AGR) has been known as a prognostic factor for cancer-related mortality. However, no study has elucidated its usefulness as a predictive factor in the era of targeted therapy, and so, we evaluated this in the present study. METHODS:We retrospectively analyzed 2012 non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Among these patients, 645 patients who had EGFR mutation and suitable pretreatment laboratory values were included. AGR was calculated 2 months before treatment and 4 months after treatment in each patient. The optimal cutoff value of AGR, and progression free survival (PFS) were also determined. RESULTS: The optimal cutoff value of AGR was 1.17, which yielded a highest HR of 1.89 (P < 0.001) for poor PFS. The median PFS was 9.5 months (95% confidential interval [CI] 7.0-10.4) in patients with pretreatment AGR < 1.17 and 13.5 months (95% CI 11.9-14.7) in those with pretreatment AGR ≥ 1.17. Pretreatment AGR showed an independent predictive value (adjusted HR 1.80,P <0.001) when age, performance status, and pre-TKI systemic treatment was adjusted for. CONCLUSIONS: We suggest that patients with NSCLC with EGFR mutations who have AGR values lower than 1.17 at the beginning of EGFR TKI treatment should be considered to have a high risk of early EGFR TKI failure.
    No preview · Article · Mar 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Background/aims: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. Methods: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. Results: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Conclusions: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.
    No preview · Article · Mar 2016 · The Korean Journal of Internal Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background and objective: There are limited data regarding serum activin-A as a biomarker for sepsis. We examined whether serum activin-A concentration could predict sepsis severity and prognosis in the management of critically ill patients with sepsis. Methods: The subjects were adult patients suspected of having sepsis and admitted to intensive care unit (ICU) from January 2013 to March 2014. Serum activin-A concentration was measured in blood sampled within 48 h after ICU admission. The primary and secondary outcomes were the diagnostic value of serum activin-A concentration as a biomarker of sepsis and the prognostic value for predicting the clinical outcomes of sepsis, respectively. Results: One hundred and thirty patients who had clinically suspected sepsis were included. Most (66.2%) were male; their median age was 65 years, and their Acute Physiology and Chronic Health Evaluation II score was 22.3. Serum activin-A concentration tended to increase with sepsis severity and differed significantly between those with non-sepsis and severe sepsis and between those with severe sepsis and septic shock. The risks of sepsis, severe sepsis and septic shock were significantly higher in patients with a serum activin-A concentration of 251, 319 and 432 pg/mL or greater, respectively. Serum activin-A concentration was significantly associated with the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, Charlson comorbidity index and ICU mortality. Conclusion: Serum activin-A was a predictor of sepsis severity and a prognostic marker in critically ill patients with sepsis. Serum activin-A concentration in the early phase of sepsis was associated with prognostic indexes on ICU admission and with ICU mortality.
    No preview · Article · Mar 2016 · Respirology
  • [Show abstract] [Hide abstract] ABSTRACT: Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF.In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled.Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage.The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used.
    No preview · Article · Mar 2016 · Medicine
  • Nakwon Kwak · Chul-Gyu Yoo · Young Whan Kim · Sung Koo Han · Jae-Joon Yim
    [Show abstract] [Hide abstract] ABSTRACT: Survival times of 219 patients diagnosed with multidrug-resistant tuberculosis were calculated and treatment outcomes compared. Mean survival of 20 patients who failed to be cured was 109.8 months (95% confidence interval [CI], 87.4-132.1), shorter than that of 150 patients who were cured (140.4 months; 95% CI, 136.1-144.7; P < .01) and that of 28 patients classified as treatment completed (138.5 months; 95% CI, 131.0-146.1; P = .02). The results demonstrate that patients with multidrug-resistant tuberculosis with poor treatment outcomes live 9 years, on average.
    No preview · Article · Feb 2016 · American journal of infection control
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: Chronic obstructive pulmonary disease (COPD) is associated with increased postoperative complications. Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classified COPD patients into four groups based on spirometry results and the severity of symptoms. The objective of this study was to evaluate the impact of GOLD groups on postoperative complications. Patients and methods: We reviewed the medical records of COPD patients who underwent preoperative spirometry between April and August 2013 at a tertiary hospital in Korea. We divided the patients into GOLD groups according to the results of spirometry and self-administered questionnaires that assessed the symptom severity and exacerbation history. GOLD groups, demographic characteristics, and operative conditions were analyzed. Results: Among a total of 405 COPD patients, 70 (17.3%) patients experienced various postoperative complications, including infection, wound, or pulmonary complications. Thoracic surgery, upper abdominal surgery, general anesthesia, large estimated blood loss during surgery, and longer anesthesia time were significant risk factors for postoperative complications. Patients in high-risk group (GOLD groups C or D) had an increased risk of postoperative complications compared to those in low-risk group (GOLD groups A or B). Conclusion: COPD patients in GOLD groups representing a high exacerbation risk have an increased risk of postoperative complications compared to those with low risk.
    No preview · Article · Feb 2016 · International Journal of COPD
  • [Show abstract] [Hide abstract] ABSTRACT: Background/aims: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). Methods: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. Results: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). Conclusions: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.
    No preview · Article · Jan 2016 · The Korean Journal of Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce.
    Preview · Article · Jan 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Platinum-based chemotherapy has conferred a modest but significant survival benefit and the introduction of newer drugs has led to achieve higher response rate in patients with advanced non-small cell lung cancer (NSCLC). We performed a phase II trial in order to evaluate the efficacy and toxicity of combination chemotherapy with vinorelbine (Navelbine) and cisplatin in advanced NSCLC. Materials and methods: Patients with previously untreated, unresectable stage IIIB or IV NSCLC with measurable lesion (s) were eligible for entry into the study. NP chemotherapy consisted of intravenous vinorelbine 25 mg/m2, on day 1 and 8, and intravenous cisplatin 80 mg/m2 on day 1; this cycle was repeated every three weeks. Results: A total of 33 patients were enrolled in the study between July 1999 and Feb 2000. Of the 30 patients deemed eligible for analysis, thirteen patients achieved a partial response and thirteen showed a stable disease. The overall response rate was 43.3%. The median duration of response was 5.7 months (95% CI: 2.8~8.5 months). The median time to progression was 7.6 months (95% CI: 5.5~9.7 months) and the overall median survival time was 15.1 months (95% CI: 9.8~20.4 months) in the intent-to-treat analysis. Chemotherapy-related grade 3 or 4 toxicities were anemia in 1.5%, leukopenia in 4.5%, nausea/vomiting in 2.3%, alopecia in 13.3%, and neurotoxicity in 3.3%. Conclusion: The combination of vinorelbine and cisplatin chemotherapy seems to be active and fairly tolerable in patients with advanced NSCLC.
    Preview · Article · Dec 2015 · Cancer Research and Treatment
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    [Show abstract] [Hide abstract] ABSTRACT: Background: According to the Fletcher-Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases. However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients. The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients. Methods: In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of <0.7. All participants had more than two spirometries, including BD response. Age groups were categorized as follows: below versus above median age or four quartiles. Results: A total of 518 participants (94.2% male; median age, 67 years; range, 42-90 years) were included. Mean absolute and predictive values of post-BD FEV1 were 1.57±0.62 L and 52.53%±18.29%, respectively. Distribution of Global initiative for Chronic Obstructive Lung Disease groups did not show statistical differences between age groups categorized by two different criteria. After grouping the population by age quartiles, the rate of FEV1 decline was faster among older patients than younger ones whether expressed as absolute value (-10.60±5.57 mL/year, -15.84±6.01 mL/year, -18.63±5.53 mL/year, 32.94±6.01 mL/year, respectively; P=0.048) or predicted value (-0.34%±0.19%/year, -0.53%±0.21%/year, -0.62%±0.19%/year, -1.26%±0.21%/year, respectively, P=0.010). Conclusion: As suggested conceptually by the Fletcher-Peto curve, annual FEV1 decline among COPD patients is accelerated among older patients than younger ones.
    Preview · Article · Dec 2015 · International Journal of COPD
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: Our study aimed to determine the predictive and prognostic values of the serum neuron-specific enolase (NSE) level in patients who had non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and who had been treated with EGFR-tyrosine kinase inhibitors (TKIs). Materials and methods: We retrospectively analyzed 151 patients who had NSCLC harboring EGFR mutations and had received either gefitinib or erlotinib as first-line treatment between 2005 and 2014. The serum NSE level was measured before initiation of EGFR-TKI treatment. Results: Of the 151 patients, 92 (60.9%) had elevated NSE levels (> 16.3 ng/mL). Patients with elevated NSE levels showed significantly shorter progression-free survival (PFS) after EGFR-TKI treatment than those with normal NSE levels (median PFS, 10.5 months vs. 15.4 months; P = .034). Multivariate analysis demonstrated that elevated NSE levels (hazard ratio [HR], 1.656; P = .017), CNS metastasis at diagnosis (HR, 1.567; P = .037), and male gender (HR, 1.840; P = .005) were independent predictive factors for short PFS. A significant difference in overall survival (OS) was observed between patient groups with elevated and normal NSE levels (median OS, 17.0 months vs. 29.1 months; P < .001), and serum NSE level remained an independent prognostic factor for OS in multivariate analysis (HR, 2.671; P < .001). Conclusion: Patients with elevated serum NSE levels have significantly shorter PFS and OS. The NSE level is both a predictive marker of EGFR-TKI treatment and a prognostic marker in EGFR-mutant NSCLC patients.
    No preview · Article · Nov 2015 · Clinical Lung Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Background/Aims: Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. Methods: A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. Results: The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug-resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. Conclusions: Neither the causative micro-organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification.
    No preview · Article · Oct 2015 · The Korean Journal of Internal Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Rapid on-site evaluation (ROSE) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been advocated to qualitatively diagnose biopsy samples. However, adequate ROSE criteria during EBUS-TBNA are unclear. The aim of this study was to determine adequacy criteria of ROSE in EBUS-TBNA samples and suggest an appropriate algorithm. Methods: Patients who underwent EBUS-TBNA for nodal evaluation between March and July 2013 at Seoul National University Hospital were included prospectively. The ROSE slides were reviewed independently by two pathologists, and the results were compared to the final pathologic results. Diagnostic yields, sensitivity, specificity, and accuracy were calculated in order to make nodal evaluations. Results: EBUS-TBNA was performed on 300 lymph nodes in 133 patients. Samples were nondiagnostic in 7.7%, 6.3%, and 1.7% of the cytologic, histologic, and overall pathologic results, respectively. On the ROSE slides, a large tissue core size (≥2 cm), microscopic anthracotic pigment (MAP), and increased lymphocyte density (LD; ≥40 cells/field [40×, mean of 10 fields]) were significantly associated with adequate final cytologic or histologic results. Malignant cells were not statistically associated with adequacy but were considered a parameter indicating an adequate diagnosis. Using four sequential criteria, tissue core size, the presence of malignant cell, MAP, and LD ≥40 cells/field, the sensitivity and accuracy rates of ROSE increased from 64.4% to 98.6% and from 64.7% to 97.3%, respectively. Conclusions: A high adequacy rate of ROSE in EBUS-TBNA can be achieved by sequentially applying four criteria: tissue core size, malignant cells, MAP, and increased LD.
    No preview · Article · Oct 2015 · The Annals of thoracic surgery
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    [Show abstract] [Hide abstract] ABSTRACT: Background Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%. Methods We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug. Results Of the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13). Conclusion Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%.
    Preview · Article · Oct 2015 · International Journal of COPD
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    [Show abstract] [Hide abstract] ABSTRACT: Background/aims: In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. Methods: This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade ≥ 2 versus < 2 was evaluated by comparing the area under the receiver operating curve (AUROC) and by classification and regression tree (CART) analysis. Results: Among 428 COPD patients, the percentages of patients classif ied into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score ≥ 15 predicted an mMRC grade ≥ 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores < 10, but they did have a lower exacerbation risk compared to those with CAT scores of 15 to 19. Conclusions: A CAT score ≥ 15 is a better indicator for the 'more symptoms group' in the management of COPD patients.
    Preview · Article · Sep 2015 · The Korean Journal of Internal Medicine
  • No preview · Article · Aug 2015 · Journal of Critical Care
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    Bin Ahn · Joohae Kim · Chul-Gyu Yoo · Young Whan Kim · Sung Koo Han · Jae-Joon Yim
    [Show abstract] [Hide abstract] ABSTRACT: Diagnostic methods for pulmonary tuberculosis (TB) have recently advanced. The aim of this study was to evaluate the changes in TB diagnostic tests that prompted the initiation of anti-TB treatment over time in South Korea, an industrialized country with an intermediate TB burden. Patients diagnosed with pulmonary TB in the first halves of 2005 and 2013 at a tertiary referral hospital were included. Diagnostic methods that prompted the initiation of anti-TB treatment were compared between the 2 groups of patients. A greater proportion of patients were diagnosed with pulmonary TB using bronchoscopy in 2013 than in 2005 (26.7% vs. 6.6%, respectively; p<0.001), while the proportion of patients clinically diagnosed with pulmonary TB was lower in 2013 than in 2005 (24.7% vs. 49.0%, respectively; p<0.001). Additionally, more patients started anti-TB treatment based on positive polymerase chain reaction (PCR) results for Mycobacterium tuberculosis DNA in 2013 than in 2005 (47.3% vs. 7.9%, respectively; p<0.001). The initiation of treatment for pulmonary TB in South Korea has become more frequently based on PCR and the use of bronchoscopic specimens.
    Preview · Article · Jul 2015 · Tuberculosis and Respiratory Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement.
    Preview · Article · Jul 2015 · BMC Cancer
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    Keunhee Oh · Myung Won Seo · Young Whan Kim · Dong-Sup Lee
    [Show abstract] [Hide abstract] ABSTRACT: Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4(+) αβ T cells and IL-17-producing γδ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4(+) αβ T cells and the percentage of IFN-γ-producing γδ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4(+) T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-γ T cells.
    Preview · Article · Jun 2015 · Immune Network

Publication Stats

2k Citations
629.36 Total Impact Points

Institutions

  • 2015
    • Pusan National University
      Busan, Busan, South Korea
  • 2004-2015
    • Seoul National University
      • • Department of Medicine
      • • Institute on Aging
      Sŏul, Seoul, South Korea
  • 2014
    • Busan National University of Education
      Busan, Busan, South Korea
  • 2009
    • Korea University
      • Department of Earth and Environmental Sciences
      Seoul, Seoul, South Korea
  • 2008
    • Inje University Paik Hospital
      Sŏul, Seoul, South Korea
    • Inje University
      • College of Medicine
      Kŭmhae, Gyeongsangnam-do, South Korea
  • 2005
    • University of Seoul
      Sŏul, Seoul, South Korea
  • 2003
    • Seoul National University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea