Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy.

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil-lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20-0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27-0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC.

Long-Term Impacts of COVID-19 on Severe Exacerbation and Mortality in Adult Asthma: A Nationwide Population-Based Cohort Study.

BACKGROUND: In adults with asthma, the long-term impact of previous coronavirus disease 2019 (COVID-19) on severe exacerbations and mortality is unclear. OBJECTIVE: We evaluated the long-term risk of severe exacerbation and mortality in adults with asthma who recovered from COVID-19. METHODS: Using the Korean National Health Insurance claim-based database, we compared the risk of severe exacerbations (emergency room visits or hospitalization) and mortality in adults with asthma aged greater than 20 years who had recovered from COVID-19 between October 8, 2020, and December 16, 2021 (COVID-19 cohort, n = 10,739) with 1:1 propensity score-matched controls (n = 10,739). RESULTS: During a median follow-up of 87 days (range, 15-448 days), the incidence rate of severe exacerbations in the COVID-19 cohort and the matched cohort was 187.3 and 119.3 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of severe exacerbation compared with the matched cohort (hazard ratio = 1.57; 95% CI, 1.06-2.32). During a median follow-up of 360 days (range, 15-721 days), the incidence rate of death in the COVID-19 and matched cohorts was 128.3 and 73.5 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of death (hazard ratio = 1.76; 95% CI, 1.33-2.30) compared with the matched cohort. When further analyzed by COVID-19 severity, severe COVID-19 was associated with a 5.12-fold (95% CI, 3.27-8.01) and 7.31-fold (95% CI, 5.41-9.88) increased risk of severe exacerbation and death, respectively, but non-severe COVID-19 was not. CONCLUSIONS: Our study shows that severe COVID-19 is associated with an increased long-term risk of severe exacerbation and mortality among individuals with asthma.

Impact of adjuvant chemotherapy on patients with stage IB non-small cell lung cancer with visceral pleural invasion.

Background: Adjuvant chemotherapy has reduced the risk of recurrence and death in stage IB non-small cell lung cancer (NSCLC) with high-risk factors; however, the impact of visceral pleural invasion (VPI) on outcomes in stage IB NSCLC treated with adjuvant chemotherapy remains controversial. The aim of this study was to explore the clinical and prognostic significance of adjuvant chemotherapy for stage IB (1-4 cm) NSCLC with VPI. Methods: This retrospective study included 251 patients admitted between January 2008 and May 2018 from four hospitals who underwent complete resection for Tumor-Node-Metastasis (TNM) 8th edition stage IB NSCLC with VPI. The relationship between adjuvant chemotherapy and overall survival (OS) or recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results: Of 251 patients with stage IB NSCLC with VPI, 122 (48.6%) received adjuvant chemotherapy after surgical resection and 129 (51.4%) were placed under observation. Multivariable analysis showed that adjuvant chemotherapy was an independent predictor of RFS [adjusted hazard ratio (aHR), 0.57; 95% confidence interval (CI): 0.33-0.96; P=0.036]. A micropapillary pattern (aHR, 2.46; 95% CI: 1.33-4.55; P=0.004) and lymphovascular invasion (aHR, 2.86; 95% CI: 1.49-5.48; P=0.002) were associated with a higher risk of recurrence. Multivariable analysis also showed that adjuvant chemotherapy was an independent predictor of OS (aHR, 0.22; 95% CI: 0.09-0.58; P=0.002). In a subgroup analysis of patients with a tumor size of 1-3 cm, adjuvant chemotherapy was associated with improved RFS and OS, and this association was maintained even when patients with VPI had additional risk factors. Conclusions: Our study shows that adjuvant chemotherapy is appropriate for patients with stage IB (1-4 cm) NSCLC with VPI, and even those with smaller tumors (1-3 cm).

Impacts of regular physical activity on hospitalisation in chronic obstructive pulmonary disease: a nationwide population-based study.

INTRODUCTION: Studies that comprehensively evaluate the association between physical activity (PA) levels, particularly by quantifying PA intensity, and healthcare use requiring emergency department (ED) visit or hospitalisation in patients with chronic obstructive pulmonary disease (COPD) are limited in Korea. METHODS: The risk of all-cause and respiratory ED visit or hospitalisation according to the presence or absence of COPD and the level of PA was evaluated in a retrospective nationwide cohort comprising 3308 subjects with COPD (COPD cohort) and 293 358 subjects without COPD (non-COPD cohort) from 2009 to 2017. RESULTS: The COPD group exhibited a higher relative risk of all-cause and respiratory ED visit or hospitalisation across all levels of PA compared with the highly active control group (≥1500 metabolic equivalents (METs)-min/week). Specifically, the highest risk was observed in the sedentary group (adjusted HR (aHR) (95% CI) = 1.70 (1.59 to 1.81) for all-cause ED visit or hospitalisation, 5.45 (4.86 to 6.12) for respiratory ED visit or hospitalisation). A 500 MET-min/week increase in PA was associated with reductions in all-cause and respiratory ED visit or hospitalisation in the COPD cohort (aHR (95% CI) = 0.92 (0.88 to 0.96) for all-cause, 0.87 (0.82 to 0.93) for respiratory cause). CONCLUSIONS: Compared with the presumed healthiest cohort, the control group with PA>1500 METs-min/week, the COPD group with reduced PA has a higher risk of ED visit or hospitalisation.

Synergistic toxicity with copper contributes to NAT2-associated isoniazid toxicity.

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5-13.2], P = 7.2 × 10-6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5-1423], P = 7.5 × 10-6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

Increased Risk of New-Onset Asthma After COVID-19: A Nationwide Population-Based Cohort Study.

BACKGROUND: Previous studies have suggested that respiratory virus infections may be associated with new-onset asthma. However, whether coronavirus disease 2019 (COVID-19) is associated with an increased risk of new-onset asthma remains unclear. OBJECTIVE: We aimed to evaluate whether recent COVID-19 increases the risk of new-onset asthma and whether COVID-19 vaccination could mitigate this risk. METHODS: We constructed 3 different study designs using the Korean National Health Insurance claim-based database: study 1: COVID-19-diagnosed subjects (COVID-19 cohort) and their matched controls; study 2: COVID-19-vaccinated subjects (vaccination cohort) and their matched controls; and study 3: vaccination cohort and their matched controls, excluding subjects diagnosed with COVID-19. RESULTS: In study 1, 1.6% of the COVID-19 cohort and 0.7% of the matched cohort developed new-onset asthma, with incidences of 31.28 and 14.55 per 1,000 person-years, respectively (P < .001). The COVID-19 cohort had a higher risk of new-onset asthma (adjusted hazard ratio [aHR] 2.14; 95% CI 1.88-2.45) than matched controls. In study 2, the vaccination cohort had a lower risk of new-onset asthma than the matched controls (aHR 0.82; 95% CI 0.76-0.89). However, among subjects without a COVID-19 diagnosis, COVID-19 vaccination was not associated with a reduced risk of new-onset asthma in study 3 (aHR 0.95; 95% CI 0.87-1.04). In subgroup analysis, the risk of new-onset asthma was significantly lower in fully vaccinated subjects and higher in older subjects and in those with diabetes mellitus than in their counterparts. CONCLUSIONS: The COVID-19 was associated with a higher incidence of new-onset asthma, which might be preventable by COVID-19 vaccination.

Association between non-cystic fibrosis bronchiectasis and the risk of incident dementia: A nationwide cohort study.

BACKGROUND: Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. OBJECTIVES: To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. METHODS: A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer's disease and vascular dementia. RESULTS: During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p < .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04-1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer's disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01-1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90-1.21). CONCLUSION: Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer's disease.

Modified Cardiovascular Sequential Organ Failure Assessment Score in Sepsis: External Validation in Intensive Care Unit Patients.

BACKGROUND: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients. METHODS: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively. RESULTS: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677-0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611-0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715-0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration. CONCLUSION: In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality.

Comparative analyses of the faecal resistome against ß-lactam and quinolone antibiotics in humans and livestock using metagenomic sequencing.

To assess the prevalence and abundance of antibiotic resistance genes in human and livestock gut microbiomes, 87 humans (healthy individuals and patients with Clostridioides difficile infection (CDI)) and 108 livestock (swine, cattle, and chickens) were enrolled. Gut microbiomes and fluoroquinolone-resistant Escherichia coli isolates were sequenced, and mobile genetic elements adjacent to the ß-lactamase (bla) and transferable quinolone resistance (qnr) genes were compared using metagenomic contigs. Each group of humans and livestock exhibited distinctive microbiota and resistome compositions in the gut. Concerning the resistome of bla and qnr, the prevalence rates between chickens and patients with CDI were the most similar (R2 = 0.46); blaTEM, blaOXA, blaCTX-M, and qnrS were highly prevalent in both groups. According to genomic and phylogenetic analyses, blaCTX-M and blaOXA expressed lineage specificity to either humans or livestock, while qnrS and blaTEM displayed a shared lineage between humans and livestock. A qnrS1 mobilome comprising five genes, including two recombinases, a transposase, and a plasmid gene, is commonly found in human and chicken gut microbiomes. Humans and chickens showed the most similar gut resistomes to ß-lactams and quinolones. QnrS and blaTEM displayed especially strong co-occurrence between the guts of humans and livestock.

Systemic sclerosis and risk of bronchiectasis: a nationwide longitudinal cohort study.

BACKGROUND: The association between systemic sclerosis and the development of bronchiectasis is unclear. This study aimed to compare the risk of bronchiectasis between individuals with systemic sclerosis and those without using a nationwide longitudinal dataset. METHODS: Using the Korean National Health Insurance Service dataset between 2010 and 2017, we identified 4845 individuals aged ≥ 20 years with systemic sclerosis and 24,225 without systemic sclerosis who were matched 1:5 by age and sex. They were followed up until the date of a bronchiectasis diagnosis, death, or December 31, 2019, whichever came first. RESULTS: During a median follow-up period of 6.0 (interquartile range, 3.2-8.7) years, 5.3% of the systemic sclerosis cohort and 1.9% of the matched cohort developed bronchiectasis, with incidence rates of 9.99 and 3.23 per 1000 person-years, respectively. Even after adjusting for potential confounders, the risk of incident bronchiectasis was significantly higher in the systemic sclerosis cohort than in the matched cohort (adjusted hazard ratio 2.63, 95% confidence interval 2.22-3.12). A subgroup analysis of individuals with systemic sclerosis revealed that the risk of incident bronchiectasis was notably higher in younger individuals aged 20-39 years (P for interaction = 0.048) and in those without other coexisting connective tissue diseases (P for interaction = 0.006) than in their counterparts. CONCLUSIONS: The risk of incident bronchiectasis is higher in individuals with systemic sclerosis than those without. Bronchiectasis should be considered one of the pulmonary manifestations related to systemic sclerosis.

Impact of air pollution on healthcare utilization in patients with bronchiectasis.

Introduction: Air pollutants are increasingly recognized to affect long-term outcomes in patients with bronchiectasis. We aimed to figure out the association between air pollutants and the risk of healthcare utilization in patients with bronchiectasis. Methods: Data for 1,029 subjects with bronchiectasis in Seoul were extracted. The air pollutants included particulate matter of 10 µm or less in diameter (PM10), particulate matter of 2.5 µm or less in diameter (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and nitrogen dioxide (NO2). The outcome was all-cause healthcare uses, defined as outpatient visit, emergency department visit, or hospitalization. The concentration-response curves between each air pollutant and relative risks for healthcare utilization were obtained. Results: There were significant correlations between air pollutant concentrations and the risk of healthcare utilization, particularly for PM10, NO2, SO2, and CO. This risk was observed even at concentrations below the recommended safe thresholds for the general population. The slopes for the association between PM10 and NO2 and the risk of healthcare use showed a logarithmic growth pattern, with the steepest increase up to 30 µg/m3 and 0.030 parts per million (ppm), respectively. The curves for SO2 and CO showed an inverted U-shaped pattern, with a peak at 0.0045 ppm and a slow upward curve, respectively. No specific trends were observed for PM2.5 and O3 and the risk of healthcare use. Discussion: Increased concentrations of PM10, NO2, SO2, and CO were associated with increased healthcare utilization in patients with bronchiectasis. For patients with bronchiectasis, there were no safety thresholds for those air pollutants, and even low levels of air pollutant exposure can negatively impact bronchiectasis outcomes.

Impact of Allergic Disease on the Risk of Mycobacterial Disease.

BACKGROUND: The association between allergic diseases and the risk of mycobacterial disease is unclear. OBJECTIVE: To evaluate the association between allergic diseases and mycobacterial diseases. METHODS: This was a population-based cohort study of 3,838,680 individuals, without prior mycobacterial disease, who participated in the 2009 National Health Screening Exam. We evaluated the incidence of mycobacterial disease (tuberculosis or nontuberculous mycobacterial infection) in participants with allergic disease (asthma, allergic rhinitis, or atopic dermatitis) and those without allergic disease. We followed the cohort up until the date of mycobacterial disease diagnosis, follow-up loss, death, or December 2018. RESULTS: During a median follow-up of 8.3 (interquartile range, 8.1-8.6) years, 0.6% of participants developed mycobacterial disease. The incidence of mycobacterial disease was significantly higher in those with allergic diseases than in those without allergic diseases (1.0 vs 0.7/1000 person-years; P < .001), with an adjusted hazard ratio of 1.13 (95% CI, 1.10-1.17). Asthma (adjusted hazard ratio, 1.37; 95% CI, 1.29-1.45) and allergic rhinitis (adjusted hazard ratio, 1.07; 95% CI, 1.04-1.11) increased the hazard of mycobacterial disease, whereas atopic dermatitis did not. The association between allergic diseases and hazard of mycobacterial disease was more prominent in older (age ≥ 65 years, P for interaction = .012) and obese (body mass index ≥ 25 kg/m2, P for interaction < .001) participants. CONCLUSION: Allergic diseases including asthma and allergic rhinitis were associated with an increased risk of mycobacterial disease, whereas atopic dermatitis was not.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort.

BACKGROUND: To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. METHODS: Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. RESULTS: Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412). CONCLUSIONS: Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Long-Term Mortality of Tuberculosis Survivors in Korea: A Population-based Longitudinal Study.

BACKGROUND: When assessing long-term tuberculosis (TB) mortality, few studies addressed the impact of behavior habits and socioeconomic status. Therefore, we aimed to evaluate long-term TB mortality and risk factors while accounting for potential confounders. METHODS: This cohort study included TB survivors (n = 82 098) aged ≥20 years between 2010 and 2017, and 1:1 age- and sex-matched controls (n = 82 098). The participants were followed up for death 1 year after study enrollment until December 2018. Long-term mortality was adjusted for behavior habits (smoking, alcohol consumption, or exercise), income level, body mass index (BMI), and comorbidities. RESULTS: During a median of 3.7 years of follow-up, the incidence rate of mortality was significantly higher in TB survivors than those in the matched controls (18.2 vs. 8.8 per 1000 person-years, P < .001). Even after adjusting for potential confounders, the mortality risk was 1.62-fold (95% confidence interval [CI], 1.54-1.70) higher in TB survivors than those in the matched controls. In addition, the hazard of mortality in TB survivors relative to matched controls significantly increased in participants aged ≥30 years, with the highest risk in those in their 40s. Male sex (adjusted hazard ratio [HR]: 2.31; 95% CI, 2.16-2.47), smoking pack-years (HR: 1.005; 95% CI, 1.004-1.006), heavy alcohol consumption (HR: 1.12; 95% CI, 1.01-1.23), and lowest income (HR: 1.27; 95% CI, 1.18-1.37) were positively associated with increased hazards for mortality, whereas higher BMI (HR: 0.91; 95% CI, .90-.92) and regular exercise (HR: 0.82; 95% CI, .76-.88) reduced the hazards of long-term mortality in TB survivors. CONCLUSIONS: The long-term mortality risk was significantly higher in TB survivors than those in the matched controls, even after adjusting for potential confounders.