Clinical Impacts of Pseudomonas aeruginosa Isolation in Patients with Bronchiectasis: Findings from KMBARC Registry.

Background:Pseudomonas aeruginosa isolation in bronchiectasis is associated with a poor prognosis, including increased hospital admissions, exacerbation, and mortality. In this study, we aimed to evaluate the clinical characteristics and outcomes of P. aeruginosa isolation from patients with bronchiectasis in South Korea. Methods: This multicenter prospective cohort study analyzed 936 patients with bronchiectasis. We examined the prevalence of P. aeruginosa isolates and other microbiological characteristics. Additionally, the clinical characteristics related to disease severity and 1-year prognosis were compared between patients with and without P. aeruginosa isolation. Propensity score matching was used to mitigate confounding biases. Results: Of the 936 patients with bronchiectasis, P. aeruginosa was isolated from 89. A total of 445 matched patients-356 patients without (non-Pseudomonas group) and 89 with (Pseudomonas group) P. aeruginosa isolation-were analyzed. The Pseudomonas group showed poorer lung function, greater involvement of radiographic bronchiectasis, and a higher proportion of cystic bronchiectasis than the non-Pseudomonas group. After one year, more patients in the Pseudomonas group were admitted for bronchiectasis than in the non-Pseudomonas group. Moreover, the Bronchiectasis Health Questionnaire scores were significantly lower in the Pseudomonas group than in the non-Pseudomonas group. Conclusions: The isolation of P. aeruginosa was independently associated with increased disease severity and poor clinical outcomes in Korean patients with bronchiectasis.

Longitudinal mortality of preserved ratio impaired spirometry in a middle-aged Asian cohort.

BACKGROUND: Although preserved ratio impaired spirometry (PRISm) has been determined to have poor prognosis, it is a heterogeneous state, and studies regarding its prognosis in Asians are limited. This study investigated the long-term all-cause and cardiovascular mortality of patients with PRISm compared with those of patients with chronic obstructive pulmonary disease (COPD) and normal individuals in the Korean middle-aged general population. METHODS: Participants were recruited between 2001 and 2002 from a community-based prospective cohort in South Korea. Mortality data were collected over a 16.5-year mean follow-up period. The all-cause and cardiovascular mortality risks of PRISm were compared between patients with COPD and healthy controls. RESULTS: The PRISm group had a mean age of 53.4 years and mean body mass index of 24.9 kg/m2; furthermore, 55.2% of the PRISm patients had never smoked, and the prevalence of comorbidities was not higher than that in the other groups. Compared with normal individuals, PRISm patients did not show increased all-cause mortality, whereas COPD patients showed increased all-cause mortality (PRISm: adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 0.85-1.65; COPD: aHR, 1.34, 95% CI, 1.07-1.69). Furthermore, the PRISm patients did not show increased cardiovascular mortality compared with normal individuals (PRISm: aHR, 1.65; 95% CI, 0.92-2.95; COPD: aHR, 1.83; 95% CI, 1.09-3.07). CONCLUSION: In our population-based cohort, all-cause and cardiovascular mortality risk did not increase in individuals with PRISm compared with normal individuals. Further studies are needed to distinguish a lower-risk subgroup of PRISm with certain characteristics, such as middle-aged, light-smoking Asians without additional cardiovascular risk.

Association between plasma sRAGE and emphysema according to the genotypes of AGER gene.

BACKGROUND: Higher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene. METHODS: We genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses. RESULTS: A total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = - 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11-0.51) and severity of emphysema (ß = - 3.28, 95% CI - 4.86 to - 1.70) in CC-genotyped participants. CONCLUSION: Plasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema.

Prevalence of depression and its associated factors in bronchiectasis: findings from KMBARC registry.

BACKGROUND: With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis. METHODS: This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). RESULTS: Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p < 0.001). Depressive symptoms inversely correlated with quality-of-life (r = - 0.704, p < 0.001) and positively correlated with fatigue severity score (r = 0.712, p < 0.001). Multivariate analysis showed that depression was significantly associated with the modified Medical Research Council dyspnea scale ≥ 2 (OR 2.960, 95% CI 1.907-4.588, p = < 0.001) and high number of exacerbations (≥ 3) in the previous year (OR 1.596, 95% CI 1.012-2.482, p = 0.041). CONCLUSIONS: Depression is common, but its association with bronchiectasis was underrecognized. It negatively affected quality-of-life and presented with fatigue symptoms. Among the bronchiectasis-related factors, dyspnea and exacerbation were closely associated with depression. Therefore, active screening for depression is necessary to optimize the treatment of bronchiectasis. TRIAL REGISTRATION: The study was registered at Clinical Research Information Service (CRiS), Republic of Korea (KCT0003088). The date of registration was June 19th, 2018.

A genome-wide association study of quantitative computed tomographic emphysema in Korean populations.

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10-8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10-6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10-6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

Prognosis of nontuberculous mycobacterial pulmonary disease according to the method of microbiologic diagnosis.

Microbiological criteria for nontuberculous mycobacterial pulmonary disease (NTM-PD) require cultures from two separate sputum or one non-sputum specimen. However, there is limited data on the progression of NTM-PD following non-sputum culture-based diagnosis. We compared the disease progression of NTM-PD diagnosed with non-sputum vs sputum cultures. We included 833 patients and divided them into sputum NTM isolation (n = 123), sputum NTM-PD (n = 558), and non-sputum NTM-PD groups (n = 152). Disease progression, defined as radiographic aggravation and therapy initiation, was compared between groups. The median observation time was 60.5 months (interquartile range, 31.4-96.0). The non-sputum NTM-PD group showed longer treatment-free survival (log-rank test; p = 0.009) and lower risk of treatment (adjusted hazard ratio [aHR] of sputum NTM-PD group, 1.36; 95% confidence interval (CI), 1.01-1.84) than the sputum NTM-PD group. The non-sputum NTM-PD group showed longer radiographic aggravation-free survival (Log-rank test; p = 0.015) and lower risk of radiographic aggravation (aHR of sputum NTM-PD group, 1.52; 95% CI, 1.06-2.19) than the sputum NTM-PD group. NTM-PD diagnosed using methods other than sputum culture showed a low risk of disease progression and progressed slower than NTM-PD diagnosed from a sputum culture. NTM-PD diagnosed using methods other than sputum culture may be a mild disease, not equivalent to NTM-PD diagnosed from sputum culture.

Increased mortality in patients with non cystic fibrosis bronchiectasis with respiratory comorbidities.

There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005-2015 data from the Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P < 0.001). Mortality risk was 1.15-fold greater in the bronchiectasis cohort than in the matched cohort (95% confidence interval [CI] 1.09-1.22); mortality was greatest among elderly patients (HR = 1.17, 95% CI 1.10-1.25) and men (HR = 1.19, 95% CI 1.10-1.29). Comorbidities over the study period significantly increased the risk of death in the bronchiectasis cohort relative to the matched cohort: asthma (adjusted HR = 1.20, 95% CI 1.11-1.30), chronic obstructive pulmonary disease (adjusted HR = 1.24, 95% CI 1.15-1.34), pneumonia (adjusted HR = 1.50, 95% CI 1.39-1.63), lung cancer (adjusted HR = 1.85, 95% CI 1.61-2.12), and cardiovascular disease (adjusted HR = 1.34, 95% CI 1.23-1.45). In contrast, there were no significant differences in the risk of death in patients without bronchiectasis-related comorbidities and the matched cohort, except in the case of non-tuberculous mycobacterial infection. In conclusion, all-cause mortality was higher in patients with bronchiectasis cohort than those without bronchiectasis, especially in elderly patients and men. Comorbidities over the study period played a major role in increasing mortality in patients with bronchiectasis relative to those without bronchiectasis.

Metabolic Syndrome and Risk of Lung Cancer: An Analysis of Korean National Health Insurance Corporation Database.

INTRODUCTION: Metabolic syndrome is known to increase the risk of several cancers. However, the association between lung cancer and metabolic syndrome remains unclear. Thus, we investigated the impact of metabolic syndrome on the incidence of lung cancer. METHODS: This study enrolled participants in a health screening program provided by the Korean National Health Insurance Service between January 2009 and December 2012. The incidence of lung cancer was observed until December 2016. We analyzed the risk of lung cancer according to the presence of metabolic syndrome, metabolic syndrome components, and number of metabolic syndrome components. RESULTS: During the study, 45 635 new cases of lung cancer were recorded among 9 586 753 participants. The presence of metabolic syndrome and all its components was positively associated with the risk of lung cancer in men after multivariate adjustment (hazard ratio [HR] of metabolic syndrome 1.15; 95% confidence interval [CI], 1.12-1.18). The risk of lung cancer increased with the number of components present. The effect of metabolic syndrome on the increasing risk of lung cancer is may be higher in underweight male ever-smokers than in other participants. CONCLUSION: Metabolic syndrome was associated with an increased risk of lung cancer in men. Moreover, the higher the number of metabolic syndrome components, the higher the risk of lung cancer.

Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. METHODS: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. RESULTS: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5-1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1-143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09-1.47), respiratory (aHR, 3.49; 95% CI, 2.21-5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33-5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097-0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631-15.736). CONCLUSION: Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.

Characteristics and Outcomes of Potentially Inappropriate Admissions to the Intensive Care Unit.

BACKGROUND: Admission of patients perceived as potentially inappropriate for intensive care is a very sensitive and controversial issue. We aimed to evaluate the use of medical resources in the intensive care unit (ICU) and outcomes of patients according to a physician's judgment of appropriateness. METHODS: ICU physicians classified patients who were admitted to the medical ICU of a tertiary hospital as appropriate or inappropriate for intensive care within 24 hours of admission. Patient outcomes including mortality were analyzed according to appropriateness. Additionally, the usage and duration of mechanical ventilation (MV), renal replacement therapy (RRT), and extracorporeal membrane oxygenation (ECMO) were analyzed according to appropriateness. RESULTS: In total, 105 patients (male, 55.4%; mean age, 62 years) were included. Twelve (11.4%) patients were considered inappropriate for intensive care based on guidance published by the Society of Critical Care Medicine through a questionnaire survey of physicians. There was no significant difference between patients considered inappropriate or appropriate for ICU admission regarding the use and duration of MV, RRT, and ECMO. In contrast, the ICU, in-hospital, 28-day, 90-day, and total mortality rates were significantly higher among patients with inappropriate admission than among patients with appropriate admission (ICU mortality: 50.0% vs. 25.8%, P=0.008; in-hospital mortality: 58.3% vs. 43.0%, P=0.028; 28-day mortality: 58.3% vs. 33.3%, P=0.019; 90-day mortality: 66.7% vs. 44.1%, P=0.023). CONCLUSIONS: Despite higher mortality, the amount of medical resources used for patients considered potentially inappropriate for intensive care did not differ from the resources used for patients considered suitable for ICU care.

Impact of mediastinal lymph node enlargement on the prognosis of idiopathic pulmonary fibrosis.

BACKGROUND: Mediastinal lymph node enlargement (LNE) is common in idiopathic pulmonary fibrosis (IPF) and is known to be associated with the severity of lung fibrosis. However, the relationship between mediastinal LNE and the prognosis of IPF has not been determined to date. METHODS: This study included patients with IPF from the interstitial lung disease registry at Seoul National University Bundang Hospital, from January 2012 to March 2016. Two thoracic radiologists independently reviewed mediastinal LNE and lung parenchymal fibrosis and ground glass opacities in chest computed tomography scans of each patient, which were obtained upon diagnosis. Mortality and admission rates were analyzed. RESULTS: In total, 132 patients (104 [78.8%] male; median age, 72 years; range, 51-84 years) were enrolled and 73 (55.3%) patients had mediastinal LNE (short axis ≥ 10 mm in diameter). Mortality was significantly higher among patients with LNE than among those without LNE (hazard ratio 2.26 [95% confidence interval 1.20-4.23], p = 0.011). Of the patients with LNE, 24.7% experienced acute exacerbation and 43.8% experienced hospital admission for respiratory causes, in comparison with 16.9% and 40.0% of patients without LNE respectively. Although patients with LNE had a tendency to have increased rate of acute exacerbation, it was not statistically significant. CONCLUSION: Mediastinal LNE in IPF is associated with increased mortality and its occurrence may be considered a poor prognostic factor in patients with IPF.

Pulmonary Histoplasmosis Identified by Video-Assisted Thoracic Surgery (VATS) Biopsy: a Case Report.

Histoplasmosis is a common endemic mycosis in North, Central, and South America, but Korea is not known as an endemic area. We treated an immunocompetent Korean patient who had histoplasmosis. A 65-year-old Korean man presented with multiple pulmonary clumps of tiny nodules in the both lungs. He had been diagnosed 40 years earlier with pulmonary tuberculosis (TB) and a fungus ball had been diagnosed 4 years earlier. He denied any history of overseas travel. The patient visited our hospital with dyspnea, blood-tinged sputum, and weight loss, which had appeared 2 months earlier. The patient underwent video-assisted thoracic surgery (VATS) lung biopsy. The biopsy sample showed necrotizing granuloma and the presence of multiple small yeast-like fungi. Tissue culture confirmed Histoplasma capsulatum, and he was finally diagnosed with pulmonary histoplasmosis. Therapy was initiated with 200 mg itraconazole orally once per day. The symptoms disappeared 1 week after the start of treatment. After 4 months, low-dose chest computed tomography showed improvement in the ground glass opacity and size of the lung lesions. In conclusion, we report a case of an immunocompetent patient who developed histoplasmosis in Korea. When a patient shows unexplainable progressive infiltrative lung lesions, histoplasmosis should be considered as one of differential diagnoses although Korea is not an endemic area.