Does COVID-19 vaccination increase the risk of interstitial lung disease at a population level?

This study showed a significantly lower incidence of ILD among COVID-19 vaccinated individuals compared to unvaccinated, suggesting that the risk of COVID-19 vaccine-related ILD is not as high as previously reported https://bit.ly/3TWzzxP.

Chronic periodontitis and risk of lung cancer: a nationwide cohort study.

Background: The impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset. Methods: This study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort). Results: During the median follow-up period of 5.1 (interquartile range, 2.8-8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94-2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40-59 age group, females, and never-smokers than their counterparts. Conclusion: We demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations.

Determination of contamination sources and geochemical reactions in groundwater of a mine area using Cu, Zn, and S-O isotopes.

To determine contamination sources and pathways, the use of multiple isotopes, including metal isotopes, can increase the reliability of environmental forensic techniques. This study differentiated contamination sources in groundwater of a mine area and elucidated geochemical processes using Cu, Zn, S-O, and O-H isotopes. Sulfate reduction and sulfide precipitation were elucidated using concentrations of dissolved sulfides, δ34SSO4, δ18OSO4, and δ66Zn. The overlying contaminated soil was possibly responsible for the contamination of groundwater at <5 mbgl, which was suggested by low δ65Cu values (0.419-1.120‰) reflecting those of soil (0.279-1.115‰). The existence of dissolved Cu as Cu(I) may prevent the increase in δ65Cu during leaching of contaminated soil in the sulfate-reducing environment. In contrast, the groundwater at >5 mbgl seemed to be highly affected by the contamination plume from the adit water, which was suggested by high SO42- concentrations (407-447 mg L-1) and δ65Cu (0.252-2.275‰) and δ66Zn (-0.105‰-0.362‰) values at a multilevel sampler approaching those of the adit seepages. Additionally, the O-H isotopic ratios were distinguished between <5 mbgl and >5 mbgl. Using δ65Cu and δ66Zn to support the determination of groundwater contamination sources may be encouraged, particularly where the isotopic signatures are distinct for each source.

The Impact of Bronchiectasis on the Clinical Characteristics of Non-Severe Asthma.

Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting ß2-agonists (P = 0.074) and mucolytics (P < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, P = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, P = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, P = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe.

The Association between Family History of Lung Cancer and Development of Lung Cancer: Analysis from the KoGES Data in Korea.

Comprehensive analyses of the association between a family history of lung cancer and lung cancer risk are limited, especially in the Korean population. We used baseline data from the Korean Genome and Epidemiology Study, conducted between 2001 and 2013. This study enrolled 198,980 individuals. Lung cancer diagnoses and family histories were determined using questionnaires. Multivariable logistic regression analysis was performed to evaluate the effect of family history on the risk of lung cancer. Of 198,980 individuals, 6296 (3.2%) and 140 (0.1%) had a family history of lung cancer and lung cancer, respectively. Individuals with a family history of lung cancer in first-degree relatives (FDRs) had a higher risk of lung cancer development than those without (adjusted odds ratio [aOR] = 2.28, 95% confidence interval [CI] = 1.11-4.66). This was more pronounced in young individuals (<60 years) who had affected relatives diagnosed with lung cancer before the age of 60 years (aOR = 3.77, 95% CI = 1.19-11.88). In subgroup analyses, this association was more evident in women, never smokers, and young individuals. A family history of lung cancer, especially in FDRs, is a significant risk factor for lung cancer development in Korea.

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.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

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).

Predicting postoperative lung function using ventilation SPECT/CT in patients with lung cancer.

Background: Single-photon emission computed tomography/computed tomography (SPECT/CT) has the advantage of assessing regional lung function. We aimed to investigate the potential of ventilation (SPECT/CT) for predicting postoperative lung function in patients with lung cancer. Methods: This retrospective study included consecutive patients with lung cancer who underwent lobectomy, preoperative ventilation, and perfusion SPECT/CT between January 2020 and December 2021. The percentage of predicted postoperative forced expiratory volume in 1 s (ppoFEV1%) and the percentage of predicted postoperative diffusion capacity of the lung for carbon monoxide (ppoDLCO%) were calculated from the % counts of each scan based on anatomical segments for lobar function. Correlation tests were performed between the predicted lung function values and actual ppoFEV1% and ppoDLCO%. Results: Among the 47 patients, 29 men and 18 women aged 67.5±9.6 years were included. Moreover, 46 ventilation and 41 perfusion SPECT/CT scans were obtained. The pulmonary function on ventilation SPECT/CT strongly correlated with perfusion SPECT/CT (correlation coefficient r=0.939 for ppoFEV1%, P<0.001; r=0.938 for ppoDLCO%, P<0.001). Both ppoFEV1% and ppoDLCO% values obtained from the ventilation and perfusion scans strongly correlated with postoperative FEV1% and DLCO% (correlation coefficient, r=0.774 and r=0.768 for ventilation; r=0.795 and r=0.751 for perfusion, each P<0.001). Conclusions: Ventilation SPECT/CT was comparable to perfusion SPECT/CT in predicting postoperative lung function.

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.

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.

Evidence-Based Guideline for the Treatment of Smoking Cessation Provided by the National Health Insurance Service in Korea.

Although major countries, such as South Korea, have developed and disseminated national smoking cessation guidelines, these efforts have been limited to developing individual societies or specialized institution-based recommendations. Therefore, evidence-based clinical guidelines are essential for developing smoking cessation interventions and promoting effective smoking cessation treatments. This guideline targets frontline clinical practitioners involved in a smoking cessation treatment support program implemented in 2015 with the support of the National Health Insurance Service. The Guideline Development Group of 10 multidisciplinary smoking cessation experts employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to review recent domestic and international research and guidelines and to determine evidence levels using the GRADE methodology. The guideline panel formulated six strong recommendations and one conditional recommendation regarding pharmacotherapy choices among general and special populations (mental disorders and chronic obstructive lung disease [COPD]). Strong recommendations favor varenicline rather than a nicotine patch or bupropion, using varenicline even if they are not ready to quit, using extended pharmacotherapy (>12 weeks) rather than standard treatment (8-12 weeks), or using pharmacotherapy for individuals with mental disorders or COPD. The conditional recommendation suggests combining varenicline with a nicotine patch instead of using varenicline alone. Aligned with the Korean Society of Medicine's clinical guideline development process, this is South Korea's first domestic smoking cessation treatment guideline that follows standardized guidelines. Primarily focusing on pharmacotherapy, it can serve as a foundation for comprehensive future smoking cessation clinical guidelines, encompassing broader treatment topics beyond medications.

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.

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.