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Abstract Background The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated. Methods This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed. Results BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively. Conclusions A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Abstract Background The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years. Methods This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable. Results During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity

Abstract Background Surgery is the mainstay of treatment for non-small cell lung cancer, but the decline in pulmonary function after surgery is noticeable and requires attention. This study aimed to evaluate longitudinal changes in pulmonary function and integrated patient-reported outcomes (PROs) after lung cancer surgery. Methods Data were obtained from a prospective cohort study, the Coordinate Approach to Cancer Patients’ Health for Lung Cancer. Changes in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) at 2 weeks, 6 months, and 1 year after surgery, and the corresponding modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive lung disease assessment test (CAT) scores were evaluated. Mixed effects model was used to investigate changes in pulmonary function and PROs. Results Among 620 patients, 477 (76.9%) underwent lobectomy, whereas 120 (19.4%) and 23 (3.7%) were treated with wedge resection/segmentectomy and bilobectomy/pneumonectomy, respectively. Both FVC and FEV1 markedly decreased 2 weeks after surgery and improved thereafter; however, they did not recover to baseline values. The corresponding mMRC dyspnea scale and CAT scores worsened immediately after surgery. The dyspnea scale of the mMRC was still higher, while CAT scores returned to baseline one year after surgery, although breathlessness and lack of energy persisted. Compared to the changes from baseline of FVC and FEV1 in patients who underwent lobectomy, patients who underwent bilobectomy/pneumonectomy showed a greater decrease in FVC and FEV1, while wedge resection/segmentectomy patients had smaller decreases in FVC and FEV1 at 2 weeks, 6 months, and 1 year after surgery. Bilobectomy/pneumonectomy patients had the highest mMRC dyspnea grade among the three groups, but the difference was not statistically significant one year after surgery. Conclusions After lung cancer surgery, pulmonary function and PROs noticeably decreased in the immediate post-operative period and improved thereafter, except for dyspnea and lack of energy. Proper information on the timeline of changes in lung function and symptoms following lung cancer surgery could guide patient care approaches after surgery. Trial registration: ClinicalTrials.gov; No.: NCT03705546; URL: www.clinicaltrials.gov

Abstract Background and objective Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI)

Abstract Background and objective This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. Methods We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco

Abstract Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration.

Abstract Background There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB. Methods In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients. Results Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients. Conclusion DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.

Abstract Background and objective The prevalence of lung cancer has been increasing in healthy elderly patients with preserved pulmonary function and without underlying lung diseases. We aimed to determine the prevalence of and risk factors for postoperative pulmonary complications (PPCs) in healthy elderly patients with non-small cell lung cancer (NSCLC) to select optimal candidates for surgical resection in this subpopulation. Methods We included 488 patients older than 70 years with normal spirometry results who underwent curative resection for NSCLC (stage IA-IIB) between 2012 and 2016. Results The median (interquartile range) age of our cohort was 73 (71–76) years. Fifty-two patients (10.7%) had PPCs. Severe PPCs like acute respiratory distress syndrome, pneumonia, and respiratory failure had prevalences of 3.7, 3.7, and 1.4%, respectively. Compared to patients without PPCs, those with PPCs were more likely to be male and current smokers; have a lower body mass index (BMI), higher American Society of Anesthesiologists (ASA) classification, more interstitial lung abnormalities (ILAs), and higher emphysema index on computed tomography (CT); and have undergone pneumonectomy or bilobectomy (all p

Abstract Background Peripheral high-density lipoprotein cholesterol (HDL-C) has been known to influx into the brain and be inversely associated with the risk of Alzheimer’s disease (AD). However, recent prospective studies of the association between HDL-C and AD have yielded inconsistent results. Here, we examined the association between the endothelial lipase (EL), which is known to be major determinant of HDL-C levels, and cognitive function. Method We compared plasma from 20 patients with Alzheimer’s disease (AD), 38 persons with mild cognitive impairment, and 51 cognitively normal controls. Plasma EL levels were measured using the enzyme-linked immunosorbent assay. Results EL levels were inversely correlated with HDL-C, as previously reported; however, there were no mean differences in plasma EL between the diagnostic groups. An analysis by classification of dementia severity according to clinical dementia rating (CDR) showed that the EL levels were significantly higher in the CDR1 group (mild dementia), as compared to CDR0 (no dementia), CDR0.5 (very mild), and CDR2 (moderate) groups. Prior to moderate dementia stage, trends analysis showed that EL levels tended to increase with increasing severity (p for trend = 0.013). Consistently, elevated EL levels were significantly correlated with the mini-mental state examination (MMSE) score (r = − 0.29, p = 0.003). Logistic regression for association between plasma EL and cognitive impairment (MMSE score ≤ 25) showed that participants with EL levels in the upper range (> 31.6 ng/ml) have a higher adjusted odds ratio of cognitive impairment than those within the lower EL range. Conclusion Findings from the present study reflect the association of EL and cognition, suggesting that the individuals with elevated plasma EL concentration are at an increased risk of cognitive impairment.

Abstract Background Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke. Methods To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β′) of tobacco smoke exposure ≥10 pack-years (β = − 0.13 and β′ = − 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations. Results Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56–1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed. Conclusions Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.

Abstract 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

Abstract Background Idiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy. Methods From January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy. Results The median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis. Conclusions RT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications. Trial registration retrospectively registered.

Abstract Background Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. Results The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. Conclusions This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy.

Abstract Background Chronic obstructive pulmonary disease (COPD) is often accompanied by multiple comorbidities, which are associated with an increased risk of exacerbation, a poor health-related quality of life, and high mortality. However, differences in comorbidity profile by race and ethnicity in COPD patients have not been fully elucidated. Methods Participants aged 40 to 79 years with spirometry-defined COPD from the U.S. National Health and Nutrition Examination Survey (NHANES) (2007–2012) and from the Korea NHANES (2007–2015) were analyzed to compare the prevalence of comorbidities by race and ethnicity group. Comorbidities were defined using questionnaire data, physical exams, and laboratory tests. Results Non-Hispanic Whites had the highest prevalence of dyslipidemia (65.5%), myocardial infarction (6.2%), osteoarthritis (40.1%), and osteoporosis (13.6%), while non-Hispanic Blacks had the highest prevalence of asthma (24.0%), hypertension (70.2%), stroke (7.3%), diabetes mellitus (DM) (23.3%), anemia (16.4%), and rheumatoid arthritis (11.9%). Compared to non-Hispanic Whites, non-Hispanic Blacks had a significantly higher prevalence of hypertension, stroke, DM, anemia, and rheumatoid arthritis after adjusting for age, sex, body mass index, and smoking status, while Hispanics had a significantly higher prevalence of DM and anemia, and Koreans had significantly lower prevalences of all comorbidities except stroke, DM, and anemia. Conclusions COPD-related comorbidities varied significantly by race and ethnicity, and different strategies may be required for the optimal management of COPD and its comorbidities in different race and ethnicity groups.

Abstract 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

Abstract Background The quick sequential organ failure assessment (qSOFA) alone has a poor sensitivity for predicting mortality in patients with complicated intra-abdominal infections, and plasma lactate levels have been shown to have a strong association with mortality in critically ill patients. Therefore, this study aimed to compare the performance of qSOFA with a score derived from a combination of qSOFA and serum lactate levels for predicting mortality in surgical patients with complicated intra-abdominal infections. Methods This retrospective study was performed at a university hospital. The medical records of 457 patients who presented to the emergency department (ED) between January 2008 and December 2016 and required emergency gastrointestinal surgery for a complicated intra-abdominal infection were reviewed retrospectively. qSOFA criteria, sequential organ failure assessment (SOFA) scores, and plasma lactate levels during their ED stay were collected. We performed area under receiver operating characteristic (AUROC) curve and sensitivity analysis to compare the performance of qSOFA alone with that of a score derived from the use of a combination of the qSOFA and lactate levels for predicting patient mortality. Results Fifty patients (10.9%) died during hospitalization. The combined qSOFA and lactate level score was superior to qSOFA alone (AUROC = 0.754 vs. 0.717, p = 0.039, respectively) and comparable to the full SOFA score (AUROC = 0.754 vs. 0.795, p = 0.127, respectively) in predicting mortality. Sensitivity and specificity of qSOFA alone were 46 and 86%, respectively, and those of the combined score were 72 and 73%, respectively (p

Abstract 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 β2-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.