Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Characteristics of subclinical tuberculosis compared to active symptomatic tuberculosis using nationwide registry cohort in Korea: prospective cohort study.

Objective: The clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis challenging. To improve our understanding of the disease progression mechanism, we aimed to identify the characteristics of subclinical TB and important predictors of symptom development. Methods: From July 2018 to June 2019, we systemically collected data from the National Surveillance System of South Korea on patients with pulmonary TB, and compared the characteristics of subclinical and active symptomatic TB patients. Results: A total of 4,636 patients with pulmonary TB were included, and the prevalence of subclinical TB was 37.1% (1,720/4,636). In subclinical TB patients, the positivity rates of acid-fast bacilli (AFB) smear and culture were 16.2 and 50.2%, respectively. Subclinical TB patients were younger (55.6 ± 19.2 vs. 60.7 ± 19.5, P < 0.001), had a higher body mass index (21.7 ± 3.1 vs. 21.0 ± 3.5, P < 0.001), less under Medicaid support, and had lower rates of chronic lung disease, AFB smear and culture positivity, and bilateral disease. Regarding the characteristic differences of individual TB-related symptoms, age was positively associated with dyspnoea and general weakness but negatively associated with chest pain, haemoptysis, and weight loss. Male patients were more prone to weight loss. Chronic lung disease was related to symptoms including cough/phlegm, dyspnoea, and haemoptysis, while autoimmune diseases were associated with fever and weight loss. Conclusions: The development of TB-related symptoms was associated with microbiological burden and clinical characteristics including underlying comorbidities, which should be evaluated carefully.

Risk of loss to follow-up among tuberculosis patients in South Korea: whom should we focus on?

Introduction: In South Korea, public-private mix (PPM) has been a key strategy in national tuberculosis (TB) control program. This study aimed to identify rate of loss to follow-up (LTFU) among TB patients in nationwide PPM institutions and their risk factors. Methods: A nationwide prospective observational study including drug susceptible TB patients diagnosed from the 1st day to the 10th day of every month between July 2018 and December 2020 in PPM institutions was designed. Multivariable survival models in which death and failure were designated as events with competing risk were used to investigate risk factors for LTFU. Results: A total of 14,942 patients were included. Of them, 356 (2.4%) had an LTFU. Risk factors for LTFU were: underweight patients (adjusted hazard ratio (aHR): 1.47, 95% CI: 1.12-1.92), patients living alone (aHR: 1.43, 95% CI: 1.16-1.76), heavy drinkers (aHR: 1.67, 95% CI: 1.16-2.39), those with malignancy (aHR: 1.49, 95% CI: 1.07-2.05), foreigners (aHR: 5.96, 95% CI: 4.51-7.89), and those with previous TB history reported as an unfavorable outcome (aHR: 4.43, 95% CI: 2.77-7.08). Effect of age on LTFU was not significant. Brief interruption of anti-TB treatment (less than two months) in current session was associated with subsequent LTFU [adjusted odds ratio: 13.09 (10.29-16.66)]. Conclusion: Identifying vulnerability of patients such as living alone, being heavy alcoholics, being foreigners or having previous TB history reported as an unfavorable outcome is required. Thorough case management for these vulnerable groups could be feasible with collaboration between public and private sectors.

Development of a Machine Learning Model for Predicting Weaning Outcomes Based Solely on Continuous Ventilator Parameters during Spontaneous Breathing Trials.

Discontinuing mechanical ventilation remains challenging. We developed a machine learning model to predict weaning outcomes using only continuous monitoring parameters obtained from ventilators during spontaneous breathing trials (SBTs). Patients who received mechanical ventilation in the medical intensive care unit at a tertiary university hospital from 2019-2021 were included in this study. During the SBTs, three waveforms and 25 numerical data were collected as input variables. The proposed convolutional neural network (CNN)-based weaning prediction model extracts features from input data with diverse lengths. Among 138 enrolled patients, 35 (25.4%) experienced weaning failure. The dataset was randomly divided into training and test sets (8:2 ratio). The area under the receiver operating characteristic curve for weaning success by the prediction model was 0.912 (95% confidence interval [CI], 0.795-1.000), with an area under the precision-recall curve of 0.767 (95% CI, 0.434-0.983). Furthermore, we used gradient-weighted class activation mapping technology to provide visual explanations of the model's prediction, highlighting influential features. This tool can assist medical staff by providing intuitive information regarding readiness for extubation without requiring any additional data collection other than SBT data. The proposed predictive model can assist clinicians in making ventilator weaning decisions in real time, thereby improving patient outcomes.

Enhancing the interferon-γ release assay through omission of nil and mitogen values.

PURPOSE: To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. METHODS: This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. RESULTS: Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09-0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06-0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05-0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. CONCLUSION: The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Safety and Immunogenicity of the ID93 + GLA-SE Tuberculosis Vaccine in BCG-Vaccinated Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93 + glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette-Guérin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. METHODS: Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2 µg ID93 + 5 µg GLA-SE, 10 µg ID93 + 5 µg GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. RESULTS: No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1 T-helper cellular immune responses. CONCLUSION: The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacterium tuberculosis-uninfected adult healthcare workers. TRIAL REGISTRATION: This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686).

Increased Healthcare Delays in Tuberculosis Patients During the First Wave of COVID-19 Pandemic in Korea: A Nationwide Cross-Sectional Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea. METHODS: We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as 'before-pandemic' and 'during-pandemic' based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment. RESULTS: Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715-1.094). CONCLUSION: The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic's impact on the national TB control project.

Interferon-γ-Inducible Chemokines as Prognostic Markers for Lung Cancer.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80-0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I-III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

Biosignal-Based Digital Biomarkers for Prediction of Ventilator Weaning Success.

We evaluated new features from biosignals comprising diverse physiological response information to predict the outcome of weaning from mechanical ventilation (MV). We enrolled 89 patients who were candidates for weaning from MV in the intensive care unit and collected continuous biosignal data: electrocardiogram (ECG), respiratory impedance, photoplethysmogram (PPG), arterial blood pressure, and ventilator parameters during a spontaneous breathing trial (SBT). We compared the collected biosignal data's variability between patients who successfully discontinued MV (n = 67) and patients who did not (n = 22). To evaluate the usefulness of the identified factors for predicting weaning success, we developed a machine learning model and evaluated its performance by bootstrapping. The following markers were different between the weaning success and failure groups: the ratio of standard deviations between the short-term and long-term heart rate variability in a Poincaré plot, sample entropy of ECG and PPG, α values of ECG, and respiratory impedance in the detrended fluctuation analysis. The area under the receiver operating characteristic curve of the model was 0.81 (95% confidence interval: 0.70-0.92). This combination of the biosignal data-based markers obtained during SBTs provides a promising tool to assist clinicians in determining the optimal extubation time.

TB Antigen-Stimulated CXCR3 Ligand Assay for Diagnosis of Tuberculous Lymphadenitis.

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

Blood lead levels in relation to smoking and chronic obstructive pulmonary disease (COPD): a study from Korean National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05). CONCLUSIONS: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.

Cancer development in patients with COPD: a retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea.

BACKGROUND: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. METHODS: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). RESULTS: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p <  0.01). Old age, male sex, lower BMI, low exercise level, history of diabetes mellitus, smoking, and COPD were independent factors associated with the development of lung cancer (p <  0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p <  0.01). CONCLUSION: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.

Host immune responses to antigens derived from a predominant strain of Mycobacterium tuberculosis.

OBJECTIVES: Beijing strain of Mycobacterium tuberculosis (M. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. This study aimed to determine host immune responses to antigens derived from the Beijing/K strain which has been highly prevalent in tuberculosis (TB) outbreaks in South Korea. METHODS: We recruited 52 TB patients and 96 healthy subjects comprising 31 individuals with latent TB infection (LTBI) and 65 TB-naïve controls based on QuantiFERON-TB Gold In-Tube (QFT-IT) tests. Blood samples were obtained for diluted whole-blood assays, multiplex bead arrays, ELISpot assays, and HLA typing. Molecular genotyping of M. tb was performed using clinical isolates. RESULTS: Active TB and LTBI groups were differentiated by TNF-α concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P < 0.001). MTBK_24800-induced IFN-γ and CXCL10 concentrations discriminated the TB-infected groups from TB-naïve controls (P < 0.001). IFN-γ-producing T cells were generated in 87.2% of TB patients in response to MTBK_24800 peptide antigens. The major immunogenic epitope was at C-terminal of the antigen, and predominantly recognized by HLA-DR4 and -DQ4. CONCLUSIONS: Measurement of IFN-γ, CXCL10, and TNF-α concentrations induced by MTBK_24790 and MTBK_24800 may contribute to improved diagnosis of TB and vaccine development in regions where the Beijing/K strain is endemic.

The Usefulness of Serum CXCR3 Ligands for Evaluating the Early Treatment Response in Tuberculosis: A Longitudinal Cohort Study.

Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB.We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into "fast" and "slow" based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as "significant."In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P < 0.01) but did not decrease in the other groups. IFN-γ levels showed no significant changes. The ability of significant decreases in marker levels to predict a fast response was evaluated. CXCL9 showed a sensitivity of 83%, and CXCL10 showed a specificity of 100%. Use of various combinations of CXCR3 ligands resulted in improvements in sensitivity (88%-93%), while specificity (92%-96%) was similar to that using single CXCR3 ligands. The decreases in CXCR3 ligand levels were less marked in the 2-month Mycobacterium tuberculosis culture-positive group than in the culture-negative group. There were significant differences in treatment outcomes in terms of 2-month culture positivity (P < 0.001), the significance of CXCL9 decreases (P < 0.01), and the significance of CXCL11 decreases (P < 0.05).In conclusion, CXCR3 ligands may be useful surrogate markers for the evaluation of early treatment response and showed utility as indicators of possible treatment failure in TB.

The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer.

We evaluated the prognostic value of F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUVmax), and sum of metabolic tumor volume (MTVsum) and total lesion glycolysis (TLGsum). The relationship between the highest SUVmax and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox's proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method.The SUVmax of the highest metabolic lesion had a significant positive correlation with MTVsum and TLGsum (P < 0.001). Upon multivariate analysis, the highest SUVmax was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTVsum was a significant prognostic factor of PFS (10-cm increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUVmax was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUVmax (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUVmax.The highest SUVmax is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUVmax might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.

Prediction of occult lymph node metastasis using volume-based PET parameters in small-sized peripheral non-small cell lung cancer.

BACKGROUND: Patients with small-sized peripheral non-small cell lung cancer (NSCLC), but without lymph node metastasis, may be optimal candidates for sublobar resection. We aim to identify the predictors of occult lymph node metastasis (OLNM) using F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in clinically node-negative, small-sized NSCLC. METHODS: One hundred thirty nine patients with small-sized NSCLC (of less than 3 cm in diameter) who underwent surgical resection with mediastinal lymph node dissection were evaluated. The maximum standardized uptake value (SUVmax), metabolic total volume (MTV) and total lesion glycolysis (TLG) of the primary tumor were measured on pretreatment PET/CT. These metabolic parameters and pathological variables were analyzed for OLNM. RESULTS: The mean tumor size was 2.11 ± 0.63 cm, and the mean number of dissected lymph nodes was 19.74 ± 12.86. Adenocarcinoma occurred in 106 patients (76.3 %). Twenty-four patients (17.2 %) had lymph node metastasis. The mean SUVmax, MTV and TLG were 4.61 ± 3.99 (0.5 ~ 17.8), 4.18 ± 6.39 (0 ~ 34.6) and 16.13 ± 28.86 (0 ~ 164.2), respectively. On receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUC) for SUVmax, MTV and TLG for node metastasis were 0.753, 0.783 and 0.775, respectively. On multivariate analysis, SUVmax (Odds ratio [OR] = 1.120, p = 0.044) and MTV (OR = 1.117, p = 0.007) were found to be risk factors for OLNM. The concordance index of MTV was 0.763, which was slightly higher than that of SUVmax. CONCLUSION: SUVmax and volume-based parameters are significant risk factors for OLNM in small peripheral NSCLC. MTV showed a better predictive performance than that of the other PET parameters; therefore, MTV may be a possible indicator for sublobar resection in clinically node-negative small-sized NSCLC.

Independent risk factors for mortality in patients with chronic obstructive pulmonary disease who undergo comprehensive cardiac evaluations.

BACKGROUND: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. OBJECTIVES: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. METHODS: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. RESULTS: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). CONCLUSIONS: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

Simple pulmonary eosinophilia found on follow-up computed tomography of oncologic patients.

OBJECTIVES: To investigate the prevalence of simple pulmonary eosinophilia (SPE) and validate CT findings of SPE found on follow-up CT of oncologic patients. METHODS: We retrospectively reviewed 6977 cases of oncologic patients who underwent chest CT. A total of 66 individuals who met criteria for having SPE were identified. CT scans were fully re-assessed by consensus of 2 radiologists in terms of characteristics of pulmonary lesions. RESULTS: The prevalence of SPE was 0.95%. A total of 193 lesions were identified and most of the lesions showed part-solid pattern (69.9%), round to ovoid contour (46.1%), ill-defined margin (90.2%), or partial halo appearance (74.8%). In addition, almost half of the lesions showed the vascular contact (49%). SPE appeared as either solitary (42.4%) or multiple lesions (57.6%). The majority of lesions were located in the periphery (76.2%), and lower lung zonal (67.4%) predominance was found. CONCLUSIONS: The frequency of SPE in oncologic patients with CT findings of GGO, part-solid lesion was high (17.5%). Therefore, when key features of CT findings suggesting SPE (part-solid nodule; ill-defined margin; peripheral distribution; and lower lung zone predominance) are newly discovered on follow-up chest CT in oncologic patients, it would be useful to correlate with blood test and do short-term follow-up in order to avoid unnecessary invasive procedure.

A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB.

BACKGROUND: The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper type 1 cells, which play a major role in cell-mediated immunity in TB. METHODS: A total of 409 subjects were enrolled. The study population comprised 186 patients with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects with a positive interferon (IFN)-γ release assay (IGRA) result, and 115 control subjects with a negative IGRA result. Whole-blood samples were collected using IGRA methodology. After incubation, plasma IFN-γ levels and two CXCR3 ligands, IFN-inducible T-cell α-chemoattractant (I-TAC, CXCL11) and monokine induced by IFN-γ (MIG, CXCL9), were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was performed. Sensitivity and specificity were based on cutoff values selected to maximize the Youden index. RESULTS: The TB antigen-stimulated levels of IFN-γ, I-TAC, and MIG were significantly increased in the active pulmonary TB group compared with all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and MIG outperformed IFN-γ in all comparisons with the IGRA-positive and -negative control groups and the non-TB pulmonary disease group. The areas under the curve (95% CI) for differentiating active pulmonary TB from all other groups were 0.893 (0.864-0.924) for IFN-γ, 0.962 (0.946-0.978) for I-TAC, and 0.944 (0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%, respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for IFN-γ. CONCLUSIONS: TB antigen-stimulated assays of I-TAC and MIG may be useful surrogate markers in the diagnosis of active pulmonary TB.