APE1/Ref-1 Inhibits Adipogenic Transcription Factors during Adipocyte Differentiation in 3T3-L1 Cells.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of APE1/Ref-1 is involved in inflammatory responses and regulation of DNA binding of transcription factors related to cell survival pathways. However, the effect of APE1/Ref-1 on adipogenic transcription factor regulation remains unknown. In this study, we investigated the effect of APE1/Ref-1 on the regulation of adipocyte differentiation in 3T3-L1 cells. During adipocyte differentiation, APE1/Ref-1 expression significantly decreased with the increased expression of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBP)-α and peroxisome proliferator-activated receptor (PPAR)-γ, and the adipocyte differentiation marker adipocyte protein 2 (aP2) in a time-dependent manner. However, APE1/Ref-1 overexpression inhibited C/EBP-α, PPAR-γ, and aP2 expression, which was upregulated during adipocyte differentiation. In contrast, silencing APE1/Ref-1 or redox inhibition of APE1/Ref-1 using E3330 increased the mRNA and protein levels of C/EBP-α, PPAR-γ, and aP2 during adipocyte differentiation. These results suggest that APE1/Ref-1 inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting that APE1/Ref-1 is a potential therapeutic target for regulating adipocyte differentiation.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.

Comparison of Predicted Exercise Capacity Equations in Adult Korean Subjects.

BACKGROUND: Maximal oxygen uptake (VO2 max) is a useful index to assess exercise capacity. However, there is no reference value for Koreans. This study aimed to compare actual VO2 max and predicted VO2 max using exercise capacity equations in Korean subjects. METHODS: This retrospective study enrolled 383 patients who underwent cardiopulmonary exercise test (CPET) with incremental maximal cycle ergometer test at Asan Medical Center from January 2020 to May 2021. Stage 1 and 2 lung cancer patients with normal lung function and healthy persons of 50 subjects who had maximal CPET were analyzed. RESULTS: The subjects were aged 65 ± 13 years and predominantly male (74%). CPET results were as follows: absolute VO2 max, 1.2 ± 0.3 L/min; body weight referenced VO2 max, 20 ± 3.9 mL/kg/min; peak work rate, 94 ± 24 watts; peak heart rate, 142 ± 21 bpm; peak O2 pulse, 10 ± 3 mL/beat; minute ventilation, 59 ± 14 L/min; peak respiratory rate, 34 ± 6 breaths per minute; and peak breathing reserve, 41 ± 18%. There was significant discordance between the measured and predicted absolute VO2 max using the Jones, Hansen, and Wasserman prediction equations developed for Caucasian population (P < 0.001). Agreement using Bland-Altman test between true and predicted absolute VO2 max was the best in Chinese equation (-0.03, 2SD = 0.55) compared to Jones (0.42, 2SD = 1.07), Hansen (0.44, 2SD = 0.86), and Wasserman (0.42, 2SD = 0.86) equations. CONCLUSION: The reference value and prediction equation from studies including primarily Caucasians may not be appropriate for Koreans. Since the mean difference is the lowest in Chinese equation, the Chinese equation might be used for the Korean adult population.

Path following Control of an Underactuated Catamaran for Recovery Maneuvers.

This paper focuses on the autonomous recovery maneuvers of an unknown underactuated practical catamaran, which returns to its initial position corresponding to the man overboard (MOB) by simply adjusting the rate of turn. This paper investigates the completion of model-based path following control for not only the traditional Williamson turn, but also complex recovery routes under time-varying disturbances. The main difficulty of model-based path following control for predicting the hydrodynamic derivatives of a practical catamaran was solved by the approximated calculation of a diagonal matrix. The second key problem of differential calculation for an underactuated model in the case of complex reference trajectories under severe disturbances was investigated. Even though this paper employs a diagonal matrix with unknown nonlinear terms, the experimental test using a small craft with payloads by remote control demonstrated the sway force per yaw moment in turning cases. Adaptive backstepping mechanisms with unknown parameters were proven by the Lyapunov theory as well as the passive-boundedness of the sway dynamics, guaranteeing the stability of sway motion in the case of unavailable sway control. The effectiveness of the algorithms of the guiding concept and error dynamics is demonstrated by the numerical simulations.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable. METHODS: We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA. RESULTS: A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009-2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73-0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30-39 years and 70-79 years, whereas for men, it was highest at ages of 70-79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE). CONCLUSION: The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Hyperuricemia Is Not Predictive of Long-Term Outcome in Patients with Stable Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although the association of hyperuricemia with an increased risk of mortality has been demonstrated in the context of acute exacerbation of chronic obstructive pulmonary disease (COPD), the long-term outcomes of hyperuricemia have not been studied in the case of stable COPD. METHODS: We retrospectively analyzed baseline data of 240 men with stable COPD enrolled in the Korea Obstructive Lung Disease cohort. We evaluated associations between serum uric acid levels and clinical parameters, risk factors for all-cause mortality, and acute exacerbation of COPD. RESULTS: The mean age of subjects was 66.4 ± 7.7 years, and the median follow-up time was 5.9 years. We identified no significant difference in terms of lung function or laboratory findings between patients with hyperuricemia and those without. Serum uric acid level was negatively associated with systemic inflammation indicated by neutrophil-lymphocyte ratio (r = -0.211, P = 0.001). Univariate Cox regression analysis revealed hyperuricemia to not be associated with an increased risk of all-cause mortality in men with stable COPD (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.250-1.370; P = 0.213). In the multivariate Cox regression model, hyperuricemia was not an independent predictor of acute exacerbation (HR, 1.383; 95% CI, 0.977-1.959; P = 0.068). CONCLUSION: Among men with stable COPD, hyperuricemia is not an independent predictor of all-cause mortality or future acute exacerbation of COPD. These results differ from those of previous studies on patients with acute exacerbation of COPD.

Study on Dynamic Behavior of Unmanned Surface Vehicle-Linked Unmanned Underwater Vehicle System for Underwater Exploration.

This paper focuses on motion analysis of a coupled unmanned surface vehicle (USV)-umbilical cable (UC)-unmanned underwater vehicle (UUV) system to investigate the interaction behavior between the vehicles and the UC in the ocean environment. For this, a new dynamic modeling method for investigating a multi-body dynamics system of this coupling system is employed. Firstly, the structure and hardware composition of the proposed system are presented. The USV and UUV are modeled as rigid-body vehicles, and the flexible UC is discretized using the catenary equation. In order to solve the nonlinear coupled dynamics of the vehicles and flexible UC, the fourth-order Runge-Kutta numerical method is implemented. In modeling the flexible UC dynamics, the shooting method is applied to solve a two-point boundary value problem of the catenary equation. The interaction between the UC and the USV-UUV system is investigated through numerical simulations in the time domain. Through the computer simulation, the behavior of the coupled USV-UC-UUV system is analyzed for three situations which can occur. In particular, variation of the UC forces and moments at the tow points and the configuration of the UC in the water are investigated.

Association Between Duration of Aminoglycoside Treatment and Outcome of Cavitary Mycobacterium avium Complex Lung Disease.

BACKGROUND: Although aminoglycosides are recommended for cavitary Mycobacterium avium complex lung disease (MAC-LD), the optimal duration of treatment is unclear. We investigated the association between duration of aminoglycoside treatment and outcomes in cavitary MAC-LD. METHODS: Among patients diagnosed with macrolide-susceptible cavitary MAC-LD between 2000 and 2013, 101 who received treatment up to August 2017 with a regimen containing aminoglycosides were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. The duration of aminoglycoside treatment was at the discretion of the attending physician. RESULTS: A total of 75 patients (74.3%) were administered aminoglycosides for ≥3 months (median 164 days), whereas the remaining 26 patients (25.7%) received treatment for <3 months (median 59 days). The overall treatment success rate was 63.4% (64/101). Patients treated with aminoglycosides for ≥3 months had a significantly higher success rate than those treated for <3 months (69.3% vs 46.2%; P = .035). Multivariate analysis revealed that aminoglycoside treatment for ≥3 months was a significant factor for treatment success (adjusted odds ratio, 3.602; 95% confidence interval, 1.249-10.390; P = .018). Recurrence occurred in 8 (22.9%) of 35 patients who were followed up for at least 3 years after the end of treatment; all 8 patients received aminoglycosides for ≥3 months. CONCLUSIONS: Patients with cavitary MAC-LD treated with aminoglycosides for ≥3 months showed higher treatment success rate than those treated for <3 months. However, treatment for ≥3 months was not associated with the development of recurrence.

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease.

BACKGROUND: Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort. METHODS: We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model. RESULTS: Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = - 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels. CONCLUSIONS: Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

Change in inhaled corticosteroid treatment and COPD exacerbations: an analysis of real-world data from the KOLD/KOCOSS cohorts.

BACKGROUND: This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines. METHODS: A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/µl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal. RESULTS: ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p < 0.001). Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs. 0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs. 0.12, p = 0.03). CONCLUSIONS: Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators. ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients' characteristics.

Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms. METHODS: We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George's Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed. RESULTS: After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference -4.7 [95% CI -7.9 to -1.6] and -4.8 [95% CI -7.9 to -1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference -5.0 [95% CI -8.6 to -1.4]) compared to no regular treatment at 12 months of follow-up. CONCLUSIONS: Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

The Ability of Different Scoring Systems to Predict Mortality in Chronic Obstructive Pulmonary Disease Patients: A Prospective Cohort Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality, therefore the prediction of mortality in COPD patients is crucial. In the current study, the abilities of different categorization systems to predict mortality in stable COPD patients from a prospective cohort were compared. METHODS: The ability to predict mortality was compared in terms of discrimination by Harrell's C (HC) index and calibration using graphical comparison among the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011, GOLD 2017, GOLD grade, BODE (BMI, Airflow Obstruction, Dyspnea, Exercise), updated BODE, BODEx (BMI, Airflow Obstruction, Dyspnea, Exacerbation), e-BODE (Exacerbation and BODE), ADO (Age, Dyspnea, Airflow Obstruction), COPD prognostic index (CPI), and simplified/optimized B-AE-D (BMI, Acute Exacerbation, Dyspnea) indexes. RESULTS: The study included 520 patients, of whom 63 died during a median 40-month follow-up period. Combined prediction systems exhibited higher discrimination properties than single predictors. The CPI exhibited the highest with a HC of 0.768, followed by the simplified B-AE-D (HC 0.761), ADO (HC 0.760), and optimized B-AE-D (HC 0.756). The BODE and its variants other than the ADO exhibited relatively lower HCs (0.656-0.705), and GOLD exhibited the lowest discrimination ability among the combined indices (HCs 0.628-0.637). Subjective symptom questionnaires such as the modified Medical Research Council (mMRC) scale (HC 0.693) and SGRQ (HC 0.679) exhibited the highest ability to predict mortality among the single indices. CONCLUSION: The ADO, simplified B-AE-D, optimized B-AE-D, and GOLD 2017 exhibited good calibration properties, but the CPI did not. The simplified and optimized B-AE-Ds and the ADO index had good discrimination and calibration properties for the prediction of mortality in stable COPD patients.

Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer.

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031-3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

Clinical Phenotypes, Comorbidities, and Exacerbations according to Serum 25-OH Vitamin D and Plasma Fibrinogen Levels in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although vitamin D deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD), the influence of vitamin D deficiency on COPD has not been fully established. Moreover, the inflammation process is associated with vitamin D deficiency in the general population. Therefore, this study aimed to determine whether clinical phenotypes, comorbidities, and exacerbation rates are affected by the level of plasma fibrinogen, well studied by an inflammatory marker in COPD patients, and 25-hydroxy (25-OH) vitamin D. METHODS: This retrospective study analyzed patients with COPD whose inflammatory marker levels, especially plasma fibrinogen and 25-OH vitamin D levels, had been examined. A correlation analysis was conducted for inflammatory markers and 25-OH vitamin D. Clinical characteristics, comorbidities and exacerbation rates were compared among four groups based on plasma fibrinogen concentrations (threshold, 350 mg/dL) and 25-OH vitamin D levels (threshold, 20 ng/mL). RESULTS: Among 611 patients with COPD, 236 were included in the study. The levels of inflammatory markers had no statistical correlation with the serum 25-OH vitamin D levels. The four groups showed no statistically significant differences in age, sex, smoking history, inhaler use, and severity of comorbidities. Patients with high plasma fibrinogen concentrations and low 25-OH vitamin D levels had lower lung function, higher severity index, and higher annual rate of severe exacerbations 12 months before (0.23/year) and after (0.41/year) the measurement of 25-OH vitamin D levels than did the other patients. CONCLUSION: Our findings suggested an interaction between vitamin D deficiency and COPD. The measurement of plasma fibrinogen concentrations could help identify a severe phenotypic group among patients with vitamin D deficiency.

Bronchial Thermoplasty in Patients with Severe Uncontrolled Asthma: First Korean Cases.

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.

In Vitro MIC Values of Rifampin and Ethambutol and Treatment Outcome in Mycobacterium avium Complex Lung Disease.

Although it is known that the in vitro MICs of rifampin and ethambutol are poorly correlated with the clinical response in Mycobacterium avium complex (MAC) lung disease (MAC-LD), evidence for this is limited. This study investigated the association between treatment outcome and the in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients who were treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MICs of antimicrobial agents were determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and tended to decrease with increasing MICs of rifampin and ethambutol, particularly at MICs of ≥8 µg/ml. Treatment success rate was significantly different between MAC isolates with MICs of ≥8 µg/ml for rifampin and ethambutol and those with MICs of <8 µg/ml for rifampin and/or ethambutol (64.9% versus 85.3%, P < 0.001). Multivariate analysis showed that an MIC of ≥8 µg/ml for both drugs and initial sputum acid-fast bacillus (AFB) smear positivity were independent risk factors for an unfavorable response (adjusted odds ratio [OR] = 3.154, 95% confidence interval [CI] = 1.641 to 6.063, and P = 0.001 for an MIC of ≥8 µg/ml; adjusted OR = 2.769, 95% CI = 1.420 to 5.399, and P = 0.003 for initial sputum AFB smear positivity). These findings suggest that the in vitro MICs of rifampin and ethambutol may be related to treatment outcome in MAC-LD.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

Serial blood eosinophils and clinical outcome in patients with chronic obstructive pulmonary disease.

BACKGROUND: Blood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies. However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated. This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients. METHODS: In total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included. Patients were stratified according to a cut-off of 300 cells/µL, and the association between eosinophil changes and all-cause mortality was analysed. The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George's Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups. RESULTS: Patients were stratified into three groups according to the blood eosinophil cut-off: persistently < 300 cells/µL (PL; n = 175), variable (V; n = 68), and persistently ≥300 cells/µL (PH; n = 56). There were no significant differences in baseline characteristics (age, sex, smoking, body mass index, use of inhaled corticosteroids, exacerbations in the previous year, FEV1 (L or % predicted), or emphysema score) among the groups. During a median follow-up of 6.0 years, the PH group had a better survival rate than the PL group (adjusted mortality rate ratio, 0.29; 95% confidence interval, 0.09-0.97; P = 0.045). The PH group also showed improved symptoms and impact domains of SGRQ score compared to the PL group. No difference was found in annual FEV1 decline or exacerbations during follow-up among the groups. CONCLUSIONS: Patients with persistently high blood eosinophils had a better survival rate than those with persistently low blood eosinophils. Serial follow-up of blood eosinophils could help to predict outcomes in COPD patients.

Prognostic significance of nuclear factor of activated T-cells 5 expression in non-small cell lung cancer patients who underwent surgical resection.

BACKGROUND: Nuclear factor of activated T-cells 5 (NFAT5) is known to be correlated with migration or invasion of tumor cells based on previous in vitro studies. The aim of this study was to analyze the relationship between NFAT5 expression and clinical prognosis in non-small cell lung cancer (NSCLC) patients who underwent surgical resection. MATERIALS AND METHODS: A total of 92 NSCLC patients who underwent surgical resection were enrolled. The tissue microarray core was obtained from surgically resected tumor specimens. NFAT5 expression was evaluated by immunohistochemistry. Relationships of NFAT5 expression with disease recurrence, overall survival, and disease-free survival (DFS) were analyzed. RESULTS: The mean age of 92 patients was 63.7 y. The median follow-up duration was 63.3 mo. Fifty-one (55%) patients exhibited positive expression of NFAT5. Disease recurrence in the NFAT5-positive group was significantly (P = 0.022) higher than that in the NFAT5-negative group. NFAT5-positive expression (odds ratio: 2.632, 95% confidence interval: 1.071-6.465, P = 0.035) and pathologic N stage (N1-2 versus N0; odds ratio: 3.174, 95% confidence interval: 1.241-8.123, P = 0.016) were independent and significant risk factors for disease recurrence. DFS of the NFAT5-positive group was significantly worse than that of the NFAT5-negative group (89.7 versus 48.7 mo, P = 0.011). A multivariate analysis identified NFAT5 expression (P < 0.029) as a significant independent risk factor for DFS of patients with postoperative pathologic T and N stages (P < 0.001 and P = 0.017, respectively). CONCLUSIONS: NFAT5 expression is a useful prognostic biomarker for NSCLC patients who underwent surgical resection.