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.

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.

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.

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.

Low morphometric complexity of emphysematous lesions predicts survival in chronic obstructive pulmonary disease patients.

OBJECTIVES: To investigate whether morphometric complexity in the lung can predict survival and act as a new prognostic marker in patients with chronic obstructive pulmonary disease (COPD). METHODS: COPD (n = 302) patients were retrospectively reviewed. All patients underwent volumetric computed tomography and pulmonary function tests at enrollment (2005-2015). For complexity analysis, we applied power law exponent of the emphysema size distribution (Dsize) as well as box-counting fractal dimension (Dbox3D) analysis. Patients' survival at February 2017 was ascertained. Univariate and multivariate Cox proportional hazards analyses were performed, and prediction performances of various combinatorial models were compared. RESULTS: Patients were 66 ± 6 years old, had 41 ± 28 pack-years' smoking history and variable GOLD stages (n = 20, 153, 108 and 21 in stages I-IV). The median follow-up time was 6.1 years (range: 0.2-11.6 years). Sixty-three patients (20.9%) died, of whom 35 died of lung-related causes. In univariate Cox analysis, lower Dsize and Dbox3D were significantly associated with both all-cause and lung-related mortality (both p < 0.001). In multivariate analysis, the backward elimination method demonstrated that Dbox3D, along with age and the BODE index, was an independent predictor of survival (p = 0.014; HR, 2.08; 95% CI, 1.16-3.71). The contributions of Dsize and Dbox3D to the combinatorial survival model were comparable with those of the emphysema index and lung-diffusing capacity. CONCLUSIONS: Low morphometric complexity in the lung is a predictor of survival in patients with COPD. KEY POINTS: • A newly suggested method for quantifying lung morphometric complexity is feasible. • Morphometric complexity measured on chest CT images predicts COPD patients' survival. • Complexity, diffusing capacity and emphysema index contribute similarly to the survival model.

Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms. METHODS: We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George's Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed. RESULTS: After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference -4.7 [95% CI -7.9 to -1.6] and -4.8 [95% CI -7.9 to -1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference -5.0 [95% CI -8.6 to -1.4]) compared to no regular treatment at 12 months of follow-up. CONCLUSIONS: Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

The Ability of Different Scoring Systems to Predict Mortality in Chronic Obstructive Pulmonary Disease Patients: A Prospective Cohort Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality, therefore the prediction of mortality in COPD patients is crucial. In the current study, the abilities of different categorization systems to predict mortality in stable COPD patients from a prospective cohort were compared. METHODS: The ability to predict mortality was compared in terms of discrimination by Harrell's C (HC) index and calibration using graphical comparison among the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011, GOLD 2017, GOLD grade, BODE (BMI, Airflow Obstruction, Dyspnea, Exercise), updated BODE, BODEx (BMI, Airflow Obstruction, Dyspnea, Exacerbation), e-BODE (Exacerbation and BODE), ADO (Age, Dyspnea, Airflow Obstruction), COPD prognostic index (CPI), and simplified/optimized B-AE-D (BMI, Acute Exacerbation, Dyspnea) indexes. RESULTS: The study included 520 patients, of whom 63 died during a median 40-month follow-up period. Combined prediction systems exhibited higher discrimination properties than single predictors. The CPI exhibited the highest with a HC of 0.768, followed by the simplified B-AE-D (HC 0.761), ADO (HC 0.760), and optimized B-AE-D (HC 0.756). The BODE and its variants other than the ADO exhibited relatively lower HCs (0.656-0.705), and GOLD exhibited the lowest discrimination ability among the combined indices (HCs 0.628-0.637). Subjective symptom questionnaires such as the modified Medical Research Council (mMRC) scale (HC 0.693) and SGRQ (HC 0.679) exhibited the highest ability to predict mortality among the single indices. CONCLUSION: The ADO, simplified B-AE-D, optimized B-AE-D, and GOLD 2017 exhibited good calibration properties, but the CPI did not. The simplified and optimized B-AE-Ds and the ADO index had good discrimination and calibration properties for the prediction of mortality in stable COPD patients.