Incidence and Healthcare Burden of Pertussis among Older Adults with and without Pre-Existing Chronic Obstructive Pulmonary Disease or Asthma in South Korea.

A retrospective cohort study was conducted to examine trends in the incidence and burden of pertussis among adults ≥50 years in South Korea, with/without pre-existing chronic obstructive pulmonary disease (COPD) or asthma. The nationwide Health Insurance Review and Assessment Service (HIRA) database was used to identify patients ≥50 years diagnosed with pertussis (2009-2018). Mean annual incidence of pertussis per 100 000 persons and overall mean incidence rate ratios (IRR) were calculated for patients with pre-existing COPD or asthma versus those with neither. Incremental healthcare costs (all-cause and pertussis-related) and healthcare utilisation (number of outpatient visits, emergency room visits, and number and length of hospitalisations) up to 12 months after, compared to 3 months before pertussis diagnosis, were also measured for each group (matched on sex, age, and Charlson Comorbidity Index). Of 1011 pertussis cases, 175 had asthma, 96 had COPD (not mutually exclusive), and 796 had neither. Overall mean pertussis incidence was 2.5, 3.4, and 0.5 for adults with pre-existing COPD, asthma, and those with neither. IRR (95% confidence interval) of pertussis for adults with pre-existing COPD and asthma was 4.9 (4.0-|6.1) and 6.7 (5.7-7.9). Both COPD-pertussis and asthma-pertussis groups had higher mean incremental all-cause costs and length of hospitalisations than the general-pertussis group 3 months following pertussis diagnosis. In conclusion, individuals ≥50 years in South Korea with pre-existing COPD or asthma were at an increased risk of being diagnosed with pertussis and had higher healthcare resource utilisation than those without these conditions.

Deep Learning Prediction of Survival in Patients with Chronic Obstructive Pulmonary Disease Using Chest Radiographs.

Background Preexisting indexes for predicting the prognosis of chronic obstructive pulmonary disease (COPD) do not use radiologic information and are impractical because they involve complex history assessments or exercise tests. Purpose To develop and to validate a deep learning-based survival prediction model in patients with COPD (DLSP) using chest radiographs, in addition to other clinical factors. Materials and Methods In this retrospective study, data from patients with COPD who underwent postbronchodilator spirometry and chest radiography from 2011-2015 were collected and split into training (n = 3475), validation (n = 435), and internal test (n = 315) data sets. The algorithm for predicting survival from chest radiographs was trained (hereafter, DLSPCXR), and then age, body mass index, and forced expiratory volume in 1 second (FEV1) were integrated within the model (hereafter, DLSPinteg). For external test, three independent cohorts were collected (n = 394, 416, and 337). The discrimination performance of DLSPCXR was evaluated by using time-dependent area under the receiver operating characteristic curves (TD AUCs) at 5-year survival. Goodness of fit was assessed by using the Hosmer-Lemeshow test. Using one external test data set, DLSPinteg was compared with four COPD-specific clinical indexes: BODE, ADO, COPD Assessment Test (CAT), and St George's Respiratory Questionnaire (SGRQ). Results DLSPCXR had a higher performance at predicting 5-year survival than FEV1 in two of the three external test cohorts (TD AUC: 0.73 vs 0.63 [P = .004]; 0.67 vs 0.60 [P = .01]; 0.76 vs 0.77 [P = .91]). DLSPCXR demonstrated good calibration in all cohorts. The DLSPinteg model showed no differences in TD AUC compared with BODE (0.87 vs 0.80; P = .34), ADO (0.86 vs 0.89; P = .51), and SGRQ (0.86 vs 0.70; P = .09), and showed higher TD AUC than CAT (0.93 vs 0.55; P < .001). Conclusion A deep learning model using chest radiographs was capable of predicting survival in patients with chronic obstructive pulmonary disease. © RSNA, 2022 Online supplemental material is available for this article.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.

Prognostic implication of bronchoalveolar lavage fluid analysis in patients with Pneumocystis jirovecii pneumonia without human immunodeficiency virus infection.

BACKGROUND: The prognostic value of bronchoalveolar lavage (BAL) fluid analysis in non-human immunodeficiency virus (HIV)-infected patients with Pneumocystis jirovecii pneumonia (PJP) has not been well elucidated. We aimed to investigate the prognostic implication of BAL fluid analysis in non-HIV patients with PJP. METHODS: The data of 178 non-HIV patients diagnosed with PJP based on the results of the polymerase chain reaction assay of BAL fluid specimens between April 2018 and December 2020 were retrospectively reviewed. The clinical characteristics, laboratory findings, and BAL fluid analysis results of patients who died within 90 days after hospital admission were compared. RESULTS: Twenty patients (11.2%) died within 90 days from admission. The neutrophil count in BAL fluid was significantly higher (median 22.0%, interquartile range [IQR] 2.0-46.0% vs. median 6.0%, IQR 2.0-18.0%, P = 0.044), while the lymphocyte count was significantly lower (median 24.0%, IQR 7.0-37.0% vs. median 41.0%, IQR 22.5-60.5%, P = 0.001) in the non-survivor group compared with that in the survivor group. In the multivariate analysis, the C-reactive protein level (odds ratio [OR] 1.093, 95% confidence interval [CI] 1.020-1.170, P = 0.011) and a BAL fluid lymphocyte count of ≤ 30% (OR 3.353, 95% CI 1.101-10.216, P = 0.033) were independently associated with mortality after adjusting for albumin and lactate dehydrogenase levels. CONCLUSION: A low lymphocyte count in BAL fluid may be a predictor of mortality in non-HIV patients with PJP.

Comparison of Predicted Exercise Capacity Equations in Adult Korean Subjects.

BACKGROUND: Maximal oxygen uptake (VO2 max) is a useful index to assess exercise capacity. However, there is no reference value for Koreans. This study aimed to compare actual VO2 max and predicted VO2 max using exercise capacity equations in Korean subjects. METHODS: This retrospective study enrolled 383 patients who underwent cardiopulmonary exercise test (CPET) with incremental maximal cycle ergometer test at Asan Medical Center from January 2020 to May 2021. Stage 1 and 2 lung cancer patients with normal lung function and healthy persons of 50 subjects who had maximal CPET were analyzed. RESULTS: The subjects were aged 65 ± 13 years and predominantly male (74%). CPET results were as follows: absolute VO2 max, 1.2 ± 0.3 L/min; body weight referenced VO2 max, 20 ± 3.9 mL/kg/min; peak work rate, 94 ± 24 watts; peak heart rate, 142 ± 21 bpm; peak O2 pulse, 10 ± 3 mL/beat; minute ventilation, 59 ± 14 L/min; peak respiratory rate, 34 ± 6 breaths per minute; and peak breathing reserve, 41 ± 18%. There was significant discordance between the measured and predicted absolute VO2 max using the Jones, Hansen, and Wasserman prediction equations developed for Caucasian population (P < 0.001). Agreement using Bland-Altman test between true and predicted absolute VO2 max was the best in Chinese equation (-0.03, 2SD = 0.55) compared to Jones (0.42, 2SD = 1.07), Hansen (0.44, 2SD = 0.86), and Wasserman (0.42, 2SD = 0.86) equations. CONCLUSION: The reference value and prediction equation from studies including primarily Caucasians may not be appropriate for Koreans. Since the mean difference is the lowest in Chinese equation, the Chinese equation might be used for the Korean adult population.

Dual versus monotherapy with bronchodilators in GOLD group B COPD patients according to baseline FEV1 level: a patient-level pooled analysis of phase-3 randomized clinical trials.

BACKGROUND: Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. METHODS: This was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV1, the St. George's Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events. RESULTS: A total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV1, reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group. CONCLUSIONS: Dual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV1 than those with higher FEV1.

A comparative study of chest CT findings regarding the effects of regional dust exposure on patients with COPD living in urban areas and rural areas near cement plants.

BACKGROUND: The clinical and radiological presentation of chronic obstructive pulmonary disease (COPD) is heterogenous depending on the characterized sources of inflammation. This study aimed to evaluate COPD phenotypes associated with specific dust exposure. METHODS: This study was designed to compare the characteristics, clinical outcomes and radiological findings between two prospective COPD cohorts representing two distinguishing regions in the Republic of Korea; COPD in Dusty Area (CODA) and the Korean Obstructive Lung Disease (KOLD) cohort. A total of 733 participants (n = 186 for CODA, and n = 547 for KOLD) were included finally. A multivariate analysis to compare lung function and computed tomography (CT) measurements of both cohort studies after adjusting for age, sex, education, body mass index, smoking status, and pack-year, Charlson comorbidity index, and frequency of exacerbation were performed by entering the level of FEV1(%), biomass exposure and COPD medication into the model in stepwise. RESULTS: The mean wall area (MWA, %) became significantly lower in COPD patients in KOLD from urban and metropolitan area than those in CODA cohort from cement dust area (mean ± standard deviation [SD]; 70.2 ± 1.21% in CODA vs. 66.8 ± 0.88% in KOLD, p = 0.028) after including FEV1 in the model. COPD subjects in KOLD cohort had higher CT-emphysema index (EI, 6.07 ± 3.06 in CODA vs. 20.0 ± 2.21 in KOLD, p < 0.001, respectively). The difference in the EI (%) was consistently significant even after further adjustment of FEV1 (6.12 ± 2.88% in CODA vs. 17.3 ± 2.10% in KOLD, p = 0.002, respectively). However, there was no difference in the ratio of mean lung density (MLD) between the two cohorts (p = 0.077). Additional adjustment for biomass parameters and medication for COPD did not alter the statistical significance after entering into the analysis with COPD medication. CONCLUSIONS: Higher MWA and lower EI were observed in COPD patients from the region with dust exposure. These results suggest that the imaging phenotype of COPD is influenced by specific environmental exposure.

Characteristics of Specialist-Diagnosed Asthma-COPD Overlap in Severe Asthma: Observations from the Korean Severe Asthma Registry (KoSAR).

BACKGROUND: While the clinical characteristics and outcomes of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the prevalence and features of ACO in patients with severe asthma are unclear. OBJECTIVES: Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry. METHODS: At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non-ACO groups, and the demographic and clinical characteristics of these two groups were compared. RESULTS: Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex- or current smokers (P < .001) compared with those in the non-ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non-ACO group. The ACO group used more inhaled long-acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006). CONCLUSION: Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.

Radiomics approach for survival prediction in chronic obstructive pulmonary disease.

OBJECTIVES: To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS). METHODS: This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. RESULTS: The five features remaining after the LASSO analysis were %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index. CONCLUSIONS: A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality. KEY POINTS: • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.

Respiratory Viruses in Acute Exacerbations of Bronchiectasis.

BACKGROUND: Bacterial infections are well known factors underlying acute exacerbations in bronchiectasis. However, viral infections may also contribute to acute exacerbations. We aimed to assess the rate of viral detection in acute exacerbations of bronchiectasis, and the associated clinical factors. METHODS: Diagnostic tests for viral and bacterial etiologies were performed in 792 patients with bronchiectasis who visited the emergency room or the respiratory care inpatient unit in a tertiary referral center in South Korea. All patients were diagnosed with bronchiectasis by chest computerized tomography and were prescribed antibiotics for a minimum of 3 days. RESULTS: Viral pathogens were detected in 202 of the 792 enrolled patients (25.5%). The most common viral pathogen isolated was influenza A virus (24.8%), followed by rhinovirus (22.4%), influenza B virus (9.8%), respiratory syncytial virus B (8.9%), and human metapneumovirus (6.1%). In 145 patients, a viral, but not bacterial, pathogen was detected, whereas no pathogens were found in 443 patients with exacerbations. Multivariable analysis revealed that female sex and chronic heart disease as a comorbidity were positively associated with viral detection in acute exacerbations of patients with bronchiectasis, whereas the presence of radiographic infiltration was negatively associated. CONCLUSION: Respiratory viruses were identified in approximately 25% of the acute exacerbations observed among patients with bronchiectasis. Of the viruses detected, influenza viruses and rhinovirus made up over 50%. More attention to viruses as possible causative pathogens for acute deteriorating symptoms in patients with bronchiectasis is warranted.

Poly(A)+ Sensing of Hybridization-Sensitive Fluorescent Oligonucleotide Probe Characterized by Fluorescence Correlation Methods.

Ribonucleic acid (RNA) plays an important role in many cellular processes. Thus, visualizing and quantifying the molecular dynamics of RNA directly in living cells is essential to uncovering their role in RNA metabolism. Among the wide variety of fluorescent probes available for RNA visualization, exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probes are useful because of their low fluorescence background. In this study, we apply fluorescence correlation methods to ECHO probes targeting the poly(A) tail of mRNA. In this way, we demonstrate not only the visualization but also the quantification of the interaction between the probe and the target, as well as of the change in the fluorescence brightness and the diffusion coefficient caused by the binding. In particular, the uptake of ECHO probes to detect mRNA is demonstrated in HeLa cells. These results are expected to provide new insights that help us better understand the metabolism of intracellular mRNA.

DJ-1 Can Replace FGF-2 for Long-Term Culture of Human Pluripotent Stem Cells in Defined Media and Feeder-Free Condition.

Conventional human pluripotent stem cell (hPSC) cultures require high concentrations of expensive human fibroblast growth factor 2 (hFGF-2) for hPSC self-renewal and pluripotency in defined media for long-term culture. The thermal instability of the hFGF-2 mandates media change every day, which makes hPSC culture costly and cumbersome. Human DJ-1 (hDJ-1) can bind to and stimulate FGF receptor-1. In this study, for the first time, we have replaced hFGF-2 with hDJ-1 in the essential eight media and maintained the human embryonic stem cells (hESCs), H9, in the defined media at feeder-free condition. After more than ten passages, H9 in both groups still successfully maintained the typical hESC morphology and high protein levels of pluripotency markers, SSEA4, Tra1-60, Oct4, Nanog, and ALP. DNA microarray revealed that more than 97% of the 21,448 tested genes, including the pluripotency markers, Sox2, Nanog, Klf4, Lin28A, Lin28B, and Myc, have similar mRNA levels between the two groups. Karyotyping revealed no chromosome abnormalities in both groups. They also differentiated sufficiently into three germ layers by forming in vitro EBs and in vivo teratomas. There were some variations in the RT-qPCR assay of several pluripotency markers. The proliferation rates and the mitochondria of both groups were also different. Taken together, we conclude that hDJ-1 can replace hFGF-2 in maintaining the self-renewal and the pluripotency of hESCs in feeder-free conditions.

Impact of Body Mass Index Change on the Prognosis of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Low body mass index (BMI) is an important prognostic factor in chronic obstructive pulmonary disease (COPD). However, the prognostic value of longitudinal BMI change in COPD has not been well studied. OBJECTIVE: We aimed to evaluate the association between longitudinal change of BMI and prognosis of COPD in Korean COPD cohort. METHODS: This study was conducted in a prospective Korean Obstructive Lung Disease (KOLD) cohort where COPD patients were recruited on an outpatient basis at 17 hospitals in South Korea. Annual BMI was measured over a period of 3 years or more. All patients were categorized into underweight (UW), normal weight (NW), and overweight (OW) groups by BMI. Clinical characteristics and outcomes including exacerbation and mortality were compared based on initial BMI grade and longitudinal change of BMI. RESULTS: This analysis included 537 COPD patients (mean age = 67.4 ± 7.9 years, male = 97.0%, mean BMI = 23.0 ± 3.1) of KOLD cohort. The proportions of UW, NW, and OW groups were 6.9% (n = 37), 68.9% (n = 370), and 24.2% (n = 130) respectively. The UW group showed lower forced expiratory volume in 1 s (FEV1) (p < 0.001), shorter 6-minute walk distance (p < 0.001), higher modified Medical Research Council score (p = 0.002), higher St. George Respiratory Questionnaire score (p < 0.001), higher emphysema index (p < 0.001) and air-trapping index (p < 0.001), and more frequent (p < 0.001) and severe exacerbations (p = 0.003). Multivariable analyses demonstrated that decrease of BMI (hazard ratio [HR] = 0.786, p = 0.038) and the descent of BMI group (HR = 3.167, p = 0.016) at 3-year follow-up along with age, initial BMI, post-bronchodilator FEV1, and severe exacerbations were significantly associated with mortality. CONCLUSIONS: This study demonstrated that BMI decrease during follow-up was independently associated with exacerbation and higher mortality of COPD, suggesting BMI reduction in COPD should be carefully managed.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable. METHODS: We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA. RESULTS: A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009-2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73-0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30-39 years and 70-79 years, whereas for men, it was highest at ages of 70-79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE). CONCLUSION: The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Hyperuricemia Is Not Predictive of Long-Term Outcome in Patients with Stable Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although the association of hyperuricemia with an increased risk of mortality has been demonstrated in the context of acute exacerbation of chronic obstructive pulmonary disease (COPD), the long-term outcomes of hyperuricemia have not been studied in the case of stable COPD. METHODS: We retrospectively analyzed baseline data of 240 men with stable COPD enrolled in the Korea Obstructive Lung Disease cohort. We evaluated associations between serum uric acid levels and clinical parameters, risk factors for all-cause mortality, and acute exacerbation of COPD. RESULTS: The mean age of subjects was 66.4 ± 7.7 years, and the median follow-up time was 5.9 years. We identified no significant difference in terms of lung function or laboratory findings between patients with hyperuricemia and those without. Serum uric acid level was negatively associated with systemic inflammation indicated by neutrophil-lymphocyte ratio (r = -0.211, P = 0.001). Univariate Cox regression analysis revealed hyperuricemia to not be associated with an increased risk of all-cause mortality in men with stable COPD (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.250-1.370; P = 0.213). In the multivariate Cox regression model, hyperuricemia was not an independent predictor of acute exacerbation (HR, 1.383; 95% CI, 0.977-1.959; P = 0.068). CONCLUSION: Among men with stable COPD, hyperuricemia is not an independent predictor of all-cause mortality or future acute exacerbation of COPD. These results differ from those of previous studies on patients with acute exacerbation of COPD.

Association Between Duration of Aminoglycoside Treatment and Outcome of Cavitary Mycobacterium avium Complex Lung Disease.

BACKGROUND: Although aminoglycosides are recommended for cavitary Mycobacterium avium complex lung disease (MAC-LD), the optimal duration of treatment is unclear. We investigated the association between duration of aminoglycoside treatment and outcomes in cavitary MAC-LD. METHODS: Among patients diagnosed with macrolide-susceptible cavitary MAC-LD between 2000 and 2013, 101 who received treatment up to August 2017 with a regimen containing aminoglycosides were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. The duration of aminoglycoside treatment was at the discretion of the attending physician. RESULTS: A total of 75 patients (74.3%) were administered aminoglycosides for ≥3 months (median 164 days), whereas the remaining 26 patients (25.7%) received treatment for <3 months (median 59 days). The overall treatment success rate was 63.4% (64/101). Patients treated with aminoglycosides for ≥3 months had a significantly higher success rate than those treated for <3 months (69.3% vs 46.2%; P = .035). Multivariate analysis revealed that aminoglycoside treatment for ≥3 months was a significant factor for treatment success (adjusted odds ratio, 3.602; 95% confidence interval, 1.249-10.390; P = .018). Recurrence occurred in 8 (22.9%) of 35 patients who were followed up for at least 3 years after the end of treatment; all 8 patients received aminoglycosides for ≥3 months. CONCLUSIONS: Patients with cavitary MAC-LD treated with aminoglycosides for ≥3 months showed higher treatment success rate than those treated for <3 months. However, treatment for ≥3 months was not associated with the development of recurrence.

Human umbilical cord blood mesenchymal stem cells expansion via human fibroblast-derived matrix and their potentials toward regenerative application.

Large expansion of human mesenchymal stem cells (MSCs) is of great interest for clinical applications. In this study, we examine the feasibility of human fibroblast-derived extracellular matrix (hFDM) as an alternative cell expansion setting. hFDM is obtained from decellularized extracellular matrix (ECM) derived from in vitro cultured human lung fibroblasts. Our study directly compares conventional platforms (tissue culture plastic (TCP), fibronectin (FN)-coated TCP) with hFDM using umbilical cord blood-derived MSCs (UCB-MSCs). Early cell morphology shows a rather rounded shape on TCP but highly elongated morphology on hFDM. Cell proliferation demonstrates that MSCs on hFDM were significantly better compared to the others in both 10 and 2% serum condition. Cell migration assay suggests that cell motility was improved and a cell migration marker CXCR4 was notably up-regulated on hFDM. MSCs differentiation into osteogenic lineage on hFDM was also very effective as examined via gene expression, von Kossa staining and alkaline phosphatase activity. In addition, as the MSCs were expanded on each substrate, transferred to 3D polymer mesh scaffolds and then cultivated for a while, the data found better cell proliferation and more CXCR4 expression with MSCs pre-conditioned on hFDM. Moreover, higher gene expression of stemness and engraftment-related markers was noticed with the hFDM group. Furthermore when UCB-MSCs expanded on TCP or hFDM were injected into emphysema (a lung disease) animal model, the results indicate that MSCs pre-conditioned on hFDM (with 2% serum) retain more advanced therapeutic efficacy on the improvement of emphysema than those on TCP. Current works demonstrate that compared to the conventional platforms, hFDM can be a promising source of cell expansion with a naturally derived biomimetic ECM microenvironment and may find some practical applications in regenerative medicine.

Effect of tiotropium inhaler use on mortality in patients with tuberculous destroyed lung: based on linkage between hospital and nationwide health insurance claims data in South Korea.

BACKGROUND: Although bronchodilator inhaler therapy can improve lung function in patients with tuberculous destroyed lung (TDL), its effect on mortality has not been studied. We evaluated the effect of tiotropium inhaler therapy on mortality in patients with TDL. METHODS: A retrospective cohort of 963 patients with TDL was followed for up to ten years by linking hospital and nationwide health insurance claims data. We compared patients receiving tiotropium inhaler with patients without tiotropium after matching with propensity scores. In addition, we elucidated the risk factors of mortality using Cox proportional hazards model. RESULTS: After the propensity score matching, the baseline characteristics were balanced in both the tiotropium group (n = 105) and the non-tiotropium group (n = 105); including mean age (63.9 vs. 64.4 years, P = 0.715), mean forced expiratory volume in 1 s (FEV1) (45.0 vs. 45.3%, P = 0.903), and others. After the propensity score matching, the tiotropium group showed better survival than the non-tiotropium group (median survival period: not reached for the tiotropium group vs. 7.24 years for the non-tiotropium group, Prentice-Wilcoxon test, P = 0.008). Multivariate Cox proportional hazard analysis revealed that tiotropium inhaler usage was associated with lower risk of mortality in the multivariate analysis (HR, 0.560; 95% CI, 0.380-0.824; P = 0.003) after adjusting age, sex, BMI, smoking history, mMRC dyspnea score, Charlson Comorbidity Index, concomitant COPD diagnosis, FEV1, X-ray severity score, and home oxygen usage. CONCLUSIONS: Our results suggest that tiotropium inhaler is associated with decreased all-cause mortality in TDL. Further prospective study is required for validation.

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease.

BACKGROUND: Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort. METHODS: We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model. RESULTS: Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = - 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels. CONCLUSIONS: Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

Change in inhaled corticosteroid treatment and COPD exacerbations: an analysis of real-world data from the KOLD/KOCOSS cohorts.

BACKGROUND: This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines. METHODS: A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/µl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal. RESULTS: ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p < 0.001). Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs. 0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs. 0.12, p = 0.03). CONCLUSIONS: Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators. ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients' characteristics.