Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections carry a high mortality rate, yet effective treatments remain scarce. CRAB infections have become increasingly common in intensive care units (ICUs), but data specifically examining CRAB pneumonia in ICU patients remain limited. This study aimed to identify factors associated with in-hospital mortality and day-14 clinical failure in ICU patients with CRAB pneumonia. Methods: Data from 173 ICU patients with CRAB pneumonia admitted to a tertiary referral hospital in the Republic of Korea between January 2018 and June 2025 were retrospectively analyzed. Multivariable logistic regression was used to identify factors independently associated with in-hospital mortality and day-14 clinical failure. Results: The median patient age was 70 years, and ventilator-associated pneumonia accounted for 76.3% of cases. In-hospital mortality reached 80.9% (140/173), and 75.7% (131/173) experienced clinical failure at day 14. After adjustment, higher serum albumin was associated with lower in-hospital mortality (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.31-0.95; p = 0.031), whereas corticosteroid use was associated with higher mortality (OR, 2.82; 95% CI, 1.23-6.50; p = 0.015). However, in an exploratory dose-based analysis among patients who received corticosteroids, prednisone-equivalent dose was not significantly associated with in-hospital mortality. For day-14 clinical failure, higher C-reactive protein and higher Sequential Organ Failure Assessment scores were associated with increased failure, while minocycline use was associated with reduced failure (OR, 0.21; CI, 0.08-0.50; p = 0.001). Conclusions: Lower albumin levels and corticosteroid use were independently associated with higher in-hospital mortality among ICU patients with CRAB pneumonia. Minocycline may offer clinical benefit, although further validation is needed.

BACKGROUND:Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for patients with advanced lung cancer harboring activating EGFR mutations. This study aimed to investigate the association between genetic polymorphisms in the EGFR signaling pathway and clinical outcomes in patients receiving EGFR-TKI therapy. METHODS:We enrolled 266 patients with advanced lung cancer treated with EGFR-TKIs and examined 30 putative functional polymorphisms across 11 genes involved in the EGFR signaling pathway. Associations between these polymorphisms and clinical outcomes were assessed. RESULTS:Among the polymorphisms analyzed, AKT1 rs2494750G>C was significantly associated with improved chemotherapy response (codominant model: odds ratio, 1.78; 95% confidence interval [CI], 1.05-2.99; P = 0.031) and prolonged progression-free survival (recessive model: hazard ratio, 0.62; 95% CI, 0.39-0.97; P = 0.037). In the luciferase reporter assays, the rs2494750C allele exhibited significantly lower promoter activity than the rs2494750G allele in H522 and A549 lung cancer cell lines (P = 0.033 and P < 0.001, respectively). AKT1 expression levels were also significantly reduced in individuals with the CC genotype compared to those with GG or GC genotypes (P = 0.034). CONCLUSION:The AKT1 rs2494750G>C polymorphism reduces promoter activity and gene expression of AKT1, potentially contributing to improved clinical outcomes in patients with advanced lung cancer treated with EGFR-TKIs.

BACKGROUND:Factors influencing the decline in forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV₁/FVC decline in patients with COPD. METHODS:This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV₁/FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV₁/FVC. RESULTS:Among 1,725 patients, 435 exhibited rapid FEV₁/FVC decline, with an annual change of -2.5%p (interquartile range, -3.5 to -2.0). Rapid FEV₁/FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV₁, higher post-BD FEV₁/FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV₁/FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV₁ decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV₁, low STAR stage, high forced mid-expiratory flow (FEF25-75%), accelerated FEV₁ decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV₁/FVC decline. CONCLUSION:We identified the risk factors for rapid FEV₁/FVC decline, including BMI, smoking, symptoms deterioration, FEV₁ decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV₁/FVC decline.

BACKGROUND:Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. METHODS:This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. RESULTS:Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). CONCLUSION:This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background Little is known about the transition to frequent exacerbators in stabilized patients with chronic obstructive pulmonary disease (COPD). Methods This study utilized data obtained from the Korean COPD Subgroup Study cohort (KOCOSS), including 511 infrequent exacerbators. The outcome for these groups was progression to frequent exacerbators. Multivariable logistic regression analysis was used to investigate the risk factors for progression. Results Within 1 year, 40 patients (7.8%) progressed to frequent exacerbators. Among patients with severe airflow limitation and those who used inhaled corticosteroids (ICS), the incidence of progression was significantly higher. The risk factors for this progression were older age (adjusted odds ratio [aOR], 2.01; 95% confidence interval [CI], 1.19 to 3.39 per 10-year increase), decreased percent-predicted post-bronchodilator forced expiratory volume in 1 second (FEV₁ %predicted, aOR, 1.32; 95% CI, 1.05 to 1.66 per 10% predicted decrease), increased blood eosinophil count (aOR, 1.20; 95% CI, 1.07 to 1.35 per 100 cells/μL increase), and use of ICS-containing inhalers (aOR, 3.30; 95% CI, 1.59 to 6.85). In stratified analysis, decreased percent-predicted post-bronchodilator FEV₁ (aOR, 1.39; 95% CI, 1.05 to 1.85 per 10%pred decrease) and ICS-containg inhalers (aOR, 4.01; 95% CI, 1.61 to 9.95) predicted progression among patients with eosinophils <300/μL, while higher eosinophils ≥300/μL showed a nonsignificant trend (aOR, 1.16; 95% CI, 1.00 to 1.36; p=0.058). Conclusion Among stable COPD patients, older age, decreased lung function, an increased eosinophil count, and use of ICS-containing inhalers were associated with progression to frequent exacerbators.

BACKGROUND:The diagnosis of tuberculous pleural effusion (TPE) often relies on pleural fluid adenosine deaminase (ADA) levels. The diagnostic utility of ADA, however, is influenced by the prevalence of tuberculosis (TB) in local populations. Malignant pleural effusion (MPE) cases can exhibit moderately elevated ADA levels comparable to those seen in TPE. As population aging potentially impacts ADA levels, global TB incidence is decreasing whereas the burden of malignancy is on the rise. Consequently, epidemiological shifts and temporal changes in ADA distribution complicate the differential diagnosis between TPE and MPE when ADA levels are within the 40-70 IU/L range. Nonetheless, data specific to this subset are scarce. METHODS:This retrospective study included consecutive patients aged > 18 years with confirmed TPE and MPE, spanning from 2012 to 2023. ADA levels in pleural fluid were categorized into three groups: < 40 IU/L, 40-70 IU/L, and > 70 IU/L. The study examined annual trends in the frequency of new cases and ADA level distributions over time and identified discriminating factors between TPE and MPE in cases with ADA levels of 40-70 IU/L. RESULTS:In total, 297 TPE and 369 MPE cases were included in this study. Over the study period, the frequency of TPE progressively declined, while that of MPE increased. In the most recent four-year period, new TPE and MPE cases with ADA levels of 40-70 IU/L occurred at comparable numbers. Multivariable analysis identified pleural fluid carcinoembryonic antigen (CEA) levels and the number of focal pleural nodules as independent predictors for MPE. Specifically, the presence of either CEA levels > 15.7 ng/mL or more than eight pleural nodules yielded the highest diagnostic accuracy with a sensitivity of 88%, specificity of 100%, and an area under the curve of 0.95. CONCLUSION:The differential diagnosis between TPE and MPE with pleural ADA levels of 40-70 IU/L has become increasingly critical due to evolving epidemiological patterns and ADA distribution changes over time. Pleural fluid CEA levels and the characteristics of pleural nodules may offer valuable guidance in distinguishing between TPE and MPE within this diagnostic gray zone.

BACKGROUND:Data on the clinical features and treatment outcomes in patients with primary pleural infection (PI) are limited. This study aimed to investigate the clinical characteristics of these patients. PATIENTS AND METHODS:In this retrospective study, patients with community-acquired PI, diagnosed based on pleural fluid analysis, were classified into postpneumonic and primary PI groups according to computed tomography (CT) findings. Clinical variables, microbiological data, and CT findings were compared between the two groups. RESULTS:Approximately 28 % of patients with community-acquired PI presented as primary PI. Treatment success rates and in-hospital or 30-day mortality were comparable between the two groups. However, compared to the postpneumonic PI group, the primary PI group was significantly younger and had lower proportions of patients with Pneumonia Severity Index classes 4-5 and RAPID (Renal, Age, Purulence, Infection source, and Dietary factors) score >3. On CT scans, subpleural abscesses were present in less than half of the patients in the primary PI group, compared to most patients in the postpneumonic PI group. Pleural enhancement and extrapleural fat proliferation were more frequently observed in patients with primary PI than in those with postpneumonic PI. In the primary PI group, Streptococcus anginosus group was the most common pathogen, accounting for nearly half of the causative organisms. CONCLUSIONS:Patients with primary PI had similar treatment outcomes compared to those with postpneumonic PI. However, different causative pathogens and radiologic findings of primary PI suggest a distinct pathogenesis of PI independent of pneumonia.

Objectives:Complicated pleural infections present significant challenges. Predominant causative microorganisms include the Streptococcus anginosus group (SAG) and Klebsiella pneumoniae (KP). However, limited data are available on the risk factors and outcomes associated with SAG-related pleural infection compared to KP-related pleural infection. Methods:This retrospective study was conducted in patients who underwent pleural drainage due to complicated pleural infection at Kyungpook National University Hospital in South Korea between January 2011 and December 2023. Clinical characteristics, drug resistance profiles, and outcomes were compared between patients with SAG-related and KP-related pleural infections. Results:A total of 432 patients were assessed. Among them, 161 (37 %) had positive pleural fluid cultures, with SAG (n=68, 42 %) and KP (n=34, 21 %) being the predominant pathogens. Thus, 102 patients with complicated pleural infection caused by SAG or KP were analyzed. SAG cases were associated with higher rates of chronic neurologic disease, lower rates of diabetes mellitus, prolonged symptom duration, elevated white blood cell counts, and positive gram stains on pleural fluid compared to KP cases. There were no significant differences observed between the two groups regarding radiological findings. SAG strains showed resistance rates exceeding 20 % to penicillin, erythromycin, tetracycline, and clindamycin, while remaining largely susceptible to commonly used third-generation cephalosporins, ampicillin, and fluoroquinolones. The in-hospital mortality rates were approximately 10 %, consistent across both groups. Conclusions:SAG-related pleural infections showed distinct clinical features, including more frequent chronic neurologic disease, but in-hospital mortality was comparable to that of KP-related infections.

BACKGROUND:Information regarding the role of the N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and the ratio of the diameter of the pulmonary artery to the diameter of the aorta (PA:A ratio) on computed tomography in predicting prognosis in patients with bronchiectasis exacerbation is limited. METHODS:Retrospectively, patients with bronchiectasis exacerbation were classified into survivors and non-survivors based on 1-year mortality. Clinical, laboratory, and radiological variables were compared between the two groups. RESULTS:Based on 1-year mortality, patients (n = 389) were classified as non-survivors (67 [17.2 %]) or survivors (322 [82.8 %]). Age, body mass index <18.5 kg/m2, ≥3 exacerbations in the previous year, NT-proBNP >404 pg/mL, and PA:A ratio >1 were independent predictors of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. In terms of the prognostic performance of various factors for predicting 1-year mortality using receiver operating characteristic curves, NT-proBNP had the highest area under the curve, followed by PA:A ratio. Furthermore, the prognostic performance of the Bronchiectasis Severity Index, FACED score, NT-proBNP, and PA:A ratio in predicting 1-year mortality was assessed in 198 patients with spirometry results. Among these variables, the Bronchiectasis Severity Index exhibited the highest area under the curve, followed by NT-proBNP and PA:A ratio. CONCLUSIONS:PA:A ratio and NT-proBNP may be valuable biomarkers for predicting 1-year mortality in patients with bronchiectasis exacerbation.

BACKGROUND:Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. METHODS:We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. RESULTS:Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. CONCLUSION:We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

BACKGROUND:COPD is a heterogeneous disease with progressive airflow limitation. Despite therapeutic advances, current treatments poorly halt COPD progression. Disease stability (DS) is a proposed treatment goal, but its clinical significance remains uncertain. RESEARCH QUESTION:What are the differences in lung function decline, exacerbation risk, and mortality between patients with COPD with and without DS? STUDY DESIGN AND METHODS:This study analyzed data from the Korean COPD Subgroup Study, a nationwide prospective cohort of patients with COPD in South Korea. Participants were ≥ 40 years of age and had a postbronchodilator FEV1/FVC ratio < 0.70. Ten-year all-cause mortality data were obtained from national death records and merged with cohort data. DS (+) was defined as the absence of moderate-to-severe exacerbations, no decline in FEV1, and no worsening of the St. George's Respiratory questionnaire score during the first year. Clinical outcomes were compared between patients with DS (+) and patients without DS (+), who were classified as DS (-). RESULTS:Among 1,639 patients analyzed, 147 (9.0%) achieved DS (+), whereas 1,492 (91.0%) were classified as DS (-). Baseline characteristics were similar between groups. Compared with the DS (-) group, the DS (+) group exhibited significantly lower rates of moderate-to-severe exacerbations (incidence rate ratio, 0.30; P = .033) and severe exacerbations (incidence rate ratio, 0.26; P = .002). Paradoxically, the annual decline in FEV1 was greater in the DS (+) group (-45.8 vs -10.3 mL/y; P < .001). Multivariable Cox regression analysis demonstrated that DS (+) status was independently associated with a significantly reduced risk of all-cause mortality (adjusted hazard ratio, 0.56; P = .036). INTERPRETATION:Patients with COPD with DS (+) showed reduced exacerbations and mortality. These findings support DS as a clinically meaningful and achievable treatment target in COPD, with potential utility in guiding personalized disease management.

INTRODUCTION:Reactive oxygen species modulator 1 (Romo1) is a novel protein that is critically involved in the intracellular production of reactive oxygen species. Evidence has revealed that Romo1 is associated with treatment outcomes of various human malignancies, including lung cancer. However, the clinical implications of this protein in surgically resected lung cancers harboring epidermal growth factor receptor (EGFR) mutations have not been investigated. METHODS:Data were collected from patients who underwent curative resection of EGFR-mutant lung adenocarcinoma. Romo1 protein expression levels were measured in the tumor tissue using immunohistochemical staining and evaluated semi-quantitatively using the histochemical score. Univariate and multivariate analyses were performed to identify the clinicopathological parameters that may be associated with clinical outcomes. RESULTS:A total of 98 samples were analyzed. Using the cutoff H score of 200, the population was classified into low (n = 73) and high (n = 25) Romo1 groups. Romo1 expression was significantly higher in smokers, patients with stage III disease, and patients who experienced recurrence after surgery (all p < 0.05). Multivariate analyses showed that advanced-stage and poorly differentiated cancers were associated with shorter disease-free survival (DFS). In addition, high Romo1 expression was independently associated with poor DFS (hazard ratio = 2.18, 95% confidence interval: 1.10-4.32, p = 0.0261). CONCLUSIONS:Our data showed that Romo1 overexpression was significantly associated with early recurrence in patients with resected EGFR-mutant lung adenocarcinoma. Although large-scale studies are required, Romo1 may play a prognostic role in this patient population.

Introduction: Data on factors related to mortality in patients with bronchiectasis exacerbation are insufficient. Computed tomography (CT) can measure the pectoralis muscle area (PMA) and is a useful tool to diagnose sarcopenia. This study aimed to evaluate whether PMA can predict mortality in patients with bronchiectasis exacerbation. Methods: Patients hospitalized due to bronchiectasis exacerbation at a single center were retrospectively divided into survivors and non-survivors based on 1-year mortality. Thereafter, a comparison of the clinical and radiologic characteristics was conducted between the two groups. Results: A total of 66 (14%) patients died at 1 year. In the multivariate analysis, age, BMI <18.4 kg/m(2), sex-specific PMA quartile, >= 3 exacerbations in the previous year, serum albumin <3.5 g/dL, cystic bronchiectasis, tuberculosis-destroyed lung, and diabetes mellitus were independent predictors for the 1-year mortality in patients hospitalized with bronchiectasis exacerbation. A lower PMA was associated with a lower overall survival rate in the survival analysis according to sex-specific quartiles of PMA. PMA had the highest area under the curve during assessment of prognostic performance in predicting the 1-year mortality. The lowest sex-specific PMA quartile group exhibited higher disease severity than the highest quartile group. Conclusions: CT-derived PMA was an independent predictor of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. Patients with lower PMA exhibited higher disease severity. These findings suggest that PMA might be a useful marker for providing additional information regarding prognosis of patients with bronchiectasis exacerbation.

Objectives: The clinical significance of bacteremia in patients with complicated pleural infection is still uncertain. We aimed to examine the incidence and clinical significance of bacteremia in patients with complicated pleural infection. Methods: This retrospective study comprised of consecutive patients who received pleural drainage due to complicated parapneumonic effusion or empyema. The clinical, laboratory, and radiologic data and clinical outcome were compared between patients with and without bacteremia. Additionally, the factors associated with overall mortality were evaluated in these patients. Results: Of 341 patients included in the analysis, 25 (7 %) had a positive blood culture. Blood culture testing added 2 % identification of causative pathogen compared to pleural fluid culture alone. By multivariable analysis, radiologic features of cavitary lesion, a RAPID score >= 5, and a positive microbial culture in pleural fluid were independently associated with bacteremia. Despite these clinical distinctions, there was ultimately no significant difference in in-hospital mortality between patients with and without bacteremia (3 vs. 4 %, p=1.0). The only factor significantly associated with overall mortality among patients with complicated pleural infections was a higher RAPID score [HR=1.96 (95 % CI=1.35-2.84)]. Conclusions: The rate of bacteremia in patients with complicated pleural infection was 7 %. Blood culture testing demonstrated limited diagnostic yield and had minimal impact on clinical outcomes compared to pleural fluid culture. Therefore, it seems that blood culture testing is more advantageous for specific patients with suspected pleural infection who have cavitary lesions or a RAPID score >= 5.

BackgroundInfluenza's potential impact on active tuberculosis (TB) development has been debated, with limited clinical evidence. To address this, we explored the association between influenza episodes and TB incidence in a national cohort of individuals with latent TB infection (LTBI).MethodsWe examined adults (≥20 years) diagnosed with LTBI between 2015 and 2020, using the Health Insurance Review and Assessment Service's national database in South Korea. We collected demographic data, comorbidities, and influenza episodes within 6 months before and after the initial LTBI diagnosis (prior vs. subsequent episode). We stratified the analysis into groups with and without TB preventive therapy (TPT).ResultsAmong 220,483 LTBI subjects, 49% received TPT, while 51% did not. The average age was 48.4 years, with 52% having comorbidities. A prior and subsequent influenza episode was identified in 3,221 and 4,580 individuals, respectively. Of these, 1,159 (0.53%) developed incident TB over an average follow-up of 1.86 years. The incidence rates of TB were comparable between individuals with and without prior and/or subsequent influenza episodes in the TPT group, but 1.4 times higher in the non-TPT group for those with such episodes. Cox proportional-hazards regression analysis indicated that influenza was not a risk factor for incident TB in the TPT group. However, a subsequent influenza episode significantly increased TB risk in the non-TPT group (hazard ratio: 1.648 [95% CI, 1.053-2.580]).ConclusionsIn individuals with LTBI not receiving TPT, experiencing an influenza episode may elevate the risk of developing active TB.

BACKGROUND:Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS:This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS:In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS:Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

BACKGROUND:Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients. METHODS:Our cross-sectional study evaluated Choi's, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV1) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD). RESULTS:In the eligible 2,180 COPD patients, lower predicted values of FEV1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations. GLI-2012 equation resulted in a lower proportion of patients being classified as FEV1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD). CONCLUSION:GLI-2012 reference equation may not accurately reflect FEV1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs.

Background/Aims Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.