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 >20 years 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 (range, 15-448) days, the incidence rate of severe exacerbation in the COVID-19 cohort and 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 to the matched cohort (hazard ratio=1.57; 95% confidence interval [CI]=1.06-2.32). During a median follow-up of 360 (range, 15-721) days, the incidence rate of death in the COVID-19 and matched cohort 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 to 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. CONCLUSION: Our study heightens that severe COVID-19 is associated with increased long-term risk of severe exacerbation and mortality among individuals with asthma.

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).

Lack of association between Inhaled Corticosteroid use based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. Methods: We retrospectively analyzed 107 COPD patients without history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion [ppb] were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. Results: The median FeNO value was 32 (Interquartile range [IQR], 19-45) ppb, and 34 (20.0%) patients were classified as high FeNO group (median 74ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥ 300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01-6.91; p = 0.049). Conclusions: High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

Impact of Rheumatoid Arthritis and Seropositivity on the Risk of Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Despite the coexistence of bronchiectasis and rheumatoid arthritis (RA) and the poor prognosis associated with the combination of conditions, to our knowledge, no longitudinal studies that comprehensively evaluated whether patients with RA have a higher risk of bronchiectasis compared with those without RA have been published. Whether seropositivity is associated with an increased risk of bronchiectasis in RA is the subject of ongoing controversy. RESEARCH QUESTION: Does RA influence the development of bronchiectasis? Is seropositivity associated with an increased risk of bronchiectasis in RA? STUDY DESIGN AND METHODS: The incidence of bronchiectasis was compared between individuals with RA (n = 50,651; seropositive rheumatoid arthritis [SPRA]: n = 35,879 and seronegative rheumatoid arthritis [SNRA]: n = 14,772) and 1:5 age- and sex-matched control patients (n = 253,255) enrolled between 2010 and 2017 in the Korean National Health Insurance Service database. The participants were followed from 1 year after RA diagnosis or the corresponding index date to the date of bronchiectasis incidence, censored date, or December 2019. RESULTS: The cumulative incidence of bronchiectasis at 9 years of follow-up was approximately 7% in participants with RA. During a median follow-up of 4.3 years (interquartile range, 2.6-6.3 years), participants with RA showed a 2.12-fold higher risk of developing bronchiectasis than matched control participants, even after adjusting for potential confounders related to bronchiectasis development (95% CI, 2.00-2.25). In an analysis of RA serologic status using a fully adjusted model, participants with SPRA and those with SNRA showed 2.34-fold (95% CI, 2.20-2.49) and 1.56-fold (95% CI, 1.40-1.73) increased risks, respectively, compared with matched control participants. INTERPRETATION: Individuals with RA had approximately twice the risk of developing bronchiectasis than matched control individuals, even after adjusting for potential confounders. The increased risk was more evident in individuals with SPRA than in those with SNRA, implying that rheumatic inflammation plays a major role in the development of RA-bronchiectasis overlap.

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.

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non-Small Cell Lung Cancer.

Purpose: It is unclear whether performing endosonography first in non-small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC. Materials and Methods: This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into 'no endosonography' and 'endosonography first' groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis. Results: In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models. Conclusion: In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

Changes in sputum microbiota during treatment for nontuberculous mycobacterial pulmonary disease.

Limited data exist on longitudinal changes in the sputum bacterial microbiome during treatment in nontuberculous mycobacterial pulmonary disease (NTM-PD) patients. We prospectively collected serial sputum samples from 14 NTM-PD patients during treatment, at the start (n = 14) and at 1 (n = 10), 3 (n = 10), 6 (n = 12), and 12 (n = 7) months. The bacterial microbiome changes were analyzed using 16S rRNA sequences (V3-V4 regions). Subgroup analysis included culture conversion (n = 9) and treatment refractory (n = 5) groups. In all patients, sputum alpha-diversity (ACE, Chao1, and Jackknife) significantly decreased during antibiotic treatment at 1, 3, 6, and 12 months compared to treatment initiation levels. Within the culture conversion group, genus/species-level beta-diversity showed differences at 1, 3, 6, and 12 months compared to treatment initiation (all p < 0.05). However, in the refractory group, there were no differences in beta-diversity at the genus/species levels in the sputum at any time point. In the linear discriminant analysis (LDA) effect sizes (LEfSe) analysis, the culture conversion group exhibited decreasing taxa at various levels (phylum/genus/species), but no significant increase in taxa was observed. LEfSe analysis of the refractory patient group revealed multiple taxa decreased during treatment. However, proportions of Veillonella dispar (LDA = 4.78), Fusobacterium periodonticum (LDA = 4.35), and Pseudomonas aeruginosa (LDA = 2.92) increased as the treatment period progressed in the refractory group. Sputum microbiota diversity decreases during NTM-PD treatment. In the culture conversion group, most taxa decrease, while some increase in the refractory group. These findings suggest that a distinct respiratory microbial community may exist in refractory NTM-PD patients compared to responsive antibiotic-treated patients.

Spontaneous Cultural Conversion Rate of Mycobacterium avium Complex Pulmonary Disease Based on BACES Severity.

BACKGROUND: Only a few clinical factors can aid in predicting spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). In this study, we aimed to evaluate whether the rate of SCC varies according to the severity of the disease in MAC-PD patients. METHODS: We retrospectively classified 373 MAC-PD patients who had undergone watchful waiting without antibiotics based on the severity assessment using the 'body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)' criteria. We evaluated the rate of SCC in MAC-PD patients based on BACES severity and analyzed the relevant factors. Results: Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severities of 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate BACES (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.44-0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16-0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. CONCLUSIONS: Lower BACES severity may be associated with SCC in MAC-PD patients.

Risk of Ischemic Heart Disease in Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study.

BACKGROUND: Subjects with chronic obstructive pulmonary disease (COPD) have a higher risk of ischemic heart disease (IHD) than individuals without COPD; however, longitudinal evidence is lacking. Therefore, we aimed to estimate the risk of IHD between COPD and control cohorts using a longitudinal nationwide database. METHODS: We used 2009-2017 data from the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC). Adult participants at least 20 years of age who underwent health examinations and without a history of COPD or IHD were included (n = 540,976). Participants were followed from January 1, 2009, until death, development of IHD, or December 31, 2019, whichever came first. RESULTS: At baseline, there were 3,421 participants with incident COPD and 537,555 participants without COPD. During a median of 8.0 years (5.3-9.1 years) of follow-up, 2.51% of the participants with COPD (n = 86) and 0.77% of the participants without COPD (n = 4,128) developed IHD, with an incidence of 52.24 and 10.91 per 10,000 person-years, respectively. Participants with COPD had a higher risk of IHD (adjusted hazard ratio, 1.55; 95% confidence interval, 1.25-1.93) than subjects without COPD. Demographics such as age, sex, body mass index, and personal health behaviors including smoking status and physical activity did not show significant interaction with the relationship between COPD and IHD (P for interaction > 0.05 for all). CONCLUSION: The results indicate that COPD is associated with the development of IHD independent of demographic characteristics and health-related behaviors. Based on these results, clinicians should closely monitor the onset of IHD in subjects with COPD.

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.

Clinical Factors for Successful Removal of Airway Silicone Stents in Patients With Post-Tuberculosis Tracheobronchial Stenosis.

BACKGROUND: After relieving stenosis with an airway silicone stent in post-tuberculosis bronchial stenosis (PTTS), stent removal is attempted if it is determined that airway patency can be maintained even after stent removal. However, the factors affecting airway stent removal are not well known. We investigate the factors that enable the successful removal of airway silicone stents in patients with PTTS. METHODS: We retrospectively analyzed PTTS patients who underwent bronchoscopic intervention from January 2004 to December 2019. Successful stent removal is defined as airway patency maintained when the stent is removed, so that reinsertion of the stent is not required. A multivariate logistic regression analysis was used to identify independent factors associated with successful stent removal at the first attempt. RESULTS: Total 344 patients were analyzed. Patients were followed up for a median of 47.9 (26.9-85.2) months after airway stent insertion. Approximately 69% of PTTS patients finally maintained airway patency after the stent was removed. Factors related to successful stent removal at the first attempt were older age and male sex. Absence of parenchymal calcification, segmental consolidation & bronchiolitis, and no trachea involved lesion were relevant to the successful stent removal. Stent dwelling for 12-24 months was associated with successful stent removal compared to a duration of less than 12 months. CONCLUSION: For patients whose airway patency is determined to be maintained even without a stent, it is necessary to attempt stent removal in consideration of factors related to successful stent removal.

Comparison of Cefepime with Piperacillin/Tazobactam Treatment in Patients with Hospital-Acquired Pneumonia.

Although cefepime and piperacillin/tazobactam are commonly prescribed for the treatment of hospital-acquired pneumonia (HAP), which one is the superior therapy remains unclear. Using Korean National Health Insurance Service data from January 2018 to December 2018, we compared the clinical outcomes of patients with HAP who were treated with cefepime and those treated with piperacillin/tazobactam. Data from 9955 adult patients with HAP, of whom 1502 (15%) received cefepime and 8453 (85%) received piperacillin/tazobactam, were retrieved for primary analysis. Tube feeding, suctioning, positioning care, and intensive care unit admission were more common among patients who received piperacillin/tazobactam. Treatment outcomes, including rates of in-hospital mortality, pneumonia-related readmission, and all-cause mortality within 6 months after discharge, were comparable between the two groups. In a subgroup analysis of data from patients who required tube feeding, the risk for in-hospital mortality was significantly higher among those who received cefepime (fully adjusted odds ratio, 1.43; 95% confidence interval, 1.04-1.97; p = 0.042). Treatment outcomes did not differ between patients who received cefepime and those who received piperacillin/tazobactam treatment, but among patients who were at risk for aspiration, such as those receiving tube feeding, those who received piperacillin/tazobactam had lower rates of in-hospital mortality.

The lung microbiota in nontuberculous mycobacterial pulmonary disease.

BACKGROUND: The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients. METHODS: We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3-V4 regions). RESULTS: Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p <0.05, and q <0.05). In contrast, Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, p<0.001, and q = 0.002). Several genera were differentially distributed between lung tissues from MAC-PD (n = 16) and M. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value. CONCLUSIONS: We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues. TRIAL REGISTRATION: Clinical Trial registration number: NCT00970801.