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Background: Chronic obstructive pulmonary disease (COPD) primarily impairs expiratory flow due to progressive airflow obstruction and reduced lung elasticity. Increasing evidence underlines the importance of inspiratory flow as a biomarker for selecting inhaler devices and providing ancillary aerodynamic information., Research Question: Does the longitudinal changes in maximum forced inspiratory flow (FIFmax) influence acute exacerbations and lung function decline in COPD patients?, Study Design and Methods: This longitudinal study observed FIFmax in COPD patients over a 7-year period from 2004 to 2020. Eligible patients were categorized into two groups based on FIFmax trajectory: the increased FIFmax group and the decreased FIFmax group. Our study assessed the annual rate of acute exacerbations and the annual decline rate of forced expiratory volume in 1 second (FEV 1 ). Subgroup analyses were conducted based on treatment status, with a focus on inhaled therapy and inhaler device usage., Results: Among the eligible 956 COPD patients, 56.5% belonged to the increased FIFmax group. After propensity score matching, the increased FIFmax group experienced lower rates of severe exacerbations (0.16/yr vs. 0.25/yr, P-value=0.017) and a slower decline in FEV 1 (0 [interquartile range (IQR), -51-71] vs. -43 [IQR, -119-6] ml/yr, P-value<0.001) compared to the decreased FIFmax group. These associations were particularly prominent in patients using specific inhaler therapies, such as DPI therapies., Interpretation: Our study revealed that the longitudinal changes in FIFmax are associated with clinical outcomes in COPD patients. Patients with increased FIFmax experienced a lower rate of severe exacerbations and a slower decline in lung function. These findings suggest the potential benefits of optimizing inspiratory flow in COPD management, though further studies are needed to confirm these observations due to potential confounding factors., (Copyright © 2024. Published by Elsevier Inc.)

Background: Mucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV 1 decline., Methods: COPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV 1 decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1-2, and ≥3., Results: Among 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116-2.020]), severe (adjusted HR=2.106 [95% CI, 1.429-3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132-2.125]). Annual FEV 1 decline was accelerated in the mucus plug group (β-coefficient=-62 [95% CI, -120 to -5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV 1 decline in mucus plug score ≥3 compared to score 0., Conclusions: Mucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV 1 declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: We aimed to elucidate the clinical factors associated with acute exacerbation and disease progression in young patients with chronic obstructive pulmonary disease (COPD)., Methods: This retrospective longitudinal observational study included patients with COPD aged between 20 and 50 years with post-bronchodilator forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC)<0.7. Eligible patients were followed up with ≥2 spirometry examinations at 1 year interval after COPD diagnosis. The primary outcome was moderate-to-severe acute exacerbation in young patients with COPD. Secondary outcomes were early initiation of regular inhalation therapy and accelerated annual post-bronchodilator FEV 1 decline., Results: A total of 342 patients were followed up during a median of 64 months. In multivariable analyses, risk factors for moderate-to-severe exacerbation were history of asthma (adjusted HR (aHR)=2.999, 95% CI=[2.074-4.335]), emphysema (aHR=1.951, 95% CI=[1.331-2.960]), blood eosinophil count >300/µL (aHR=1.469, 95% CI=[1.038-2.081]) and low FEV 1 (%) (aHR=0.979, 95% CI=[0.970-0.987]). A history of asthma, sputum, blood eosinophil count >300/µL, low FEV 1 (%) and low diffusing capacity of the lung for carbon monoxide (DL CO ) (%) were identified as clinical factors associated with the early initiation of regular inhalation therapy. The risk factors associated with worsened FEV 1 decline were increasing age, female sex, history of pulmonary tuberculosis, sputum, low FEV 1 (%) and low DL CO (%)., Conclusions: In young COPD patients, specific high-risk features of acute exacerbation and disease progression need to be identified, including a history of previous respiratory diseases, current respiratory symptoms, blood eosinophil counts, and structural or functional pulmonary impairment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker., Methods: This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow obstruction., Results: We analyzed next-generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in combination of DNMT3A, TET2, and PPM1D (DTP), DNA methyltransferase 3 alpha (DNMT3A), and protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) genes than in never- or ex-smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (adjusted odds ratio [aOR], 2.80; 95% confidence interval [CI], 1.01 to 7.79) (aOR, 4.03; 95% CI, 1.09 to 14.0). Patients with moderate-to-severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL transcriptional regulator 1 (ASXL1) genes was significantly associated with history of mild, severe, and total acute exacerbation., Conclusion: Given that CHIP in specific genes was significantly associated with current smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management., (© 2024. The Author(s).)

Background and Objective: When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD)., Methods: We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO 2 , O 3 , PM 2.5 , SO 2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF 25%-75% ) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated., Results: A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO 2 (OR = 1.10, 95% CI = 1.08-1.12), O 3 (OR = 1.03, 95% CI = 1.00-1.05), PM 2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO 2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly., Conclusion: The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD., (© 2024 Asian Pacific Society of Respirology.)

Higher functionality should be achieved within the device-level switching characteristics to secure the operational possibility of mixed-signal data processing within a memristive crossbar array. This work investigated electroforming-free Ta/HfO 2 /RuO 2 resistive switching devices for digital- and analog-type applications through various structural and electrical analyses. The multiphase reset behavior, induced by the conducting filament modulation and oxygen vacancy generation (annihilation) in the HfO 2 layer by interacting with the Ta (RuO 2 ) electrode, was utilized for the switching mode change. Therefore, a single device can manifest stable binary switching between low and high resistance states for the digital mode and the precise 8-bit conductance modulation (256 resistance values) via an optimized pulse application for the analog mode. An in-depth analysis of the operation in different modes and comparing memristors with different electrode structures validate the proposed mechanism. The Ta/HfO 2 /RuO 2 resistive switching device is feasible for a mixed-signal processable memristive array.

Background: Different progressions or prognoses of chronic obstructive pulmonary disease (COPD) have been reported according to structural abnormalities based on chest computed tomography (CT). This study aimed to investigate whether different structural abnormalities independently affect annual lung function changes and clinical prognosis in patients with COPD., Methods: This longitudinal multicenter observational study was conducted using the KOCOSS cohort (NCT02800499) database in Korea from January 2012 to December 2019. For COPD patients with chest CT findings at baseline enrolment and longitudinal spirometric data, annual forced expiratory volume in 1 s (FEV 1 ) decline rate (mL/year) and clinical outcomes were compared according to structural abnormalities, including emphysema, bronchiectasis (BE), and tuberculosis-destroyed lung (TDL). We estimated the adjusted annual FEV 1 changes using a mixed-effect linear regression model., Results: Among the enrolled 237 patients, 152 showed structural abnormalities. Emphysema, BE, and TDL were observed in 119 (78.3%), 28 (18.4%), and 27 (17.8%) patients, respectively. The annual decline in FEV 1 was faster in COPD patients with structural abnormalities than those without (β = -70.6 mL/year, P-value = 0.039). BE/TDL-dominant or emphysema-dominant structural abnormality contributed to an accelerated annual FEV 1 decline compared to no structural abnormality (BE/TDL-dominant, β = -103.7 mL/year, P-value = 0.043; emphysema-dominant, β = -84.1 mL/year, P-value = 0.018). Structural abnormalities made no significant differences in acute exacerbation rate and mortality., Conclusion: The lung function decline rate in COPD differed according to structural abnormalities on CT. These findings may suggest that more focus should be placed on earlier intervention or regular follow-up with spirometry in COPD patients with BE or TDL on chest CT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kwang Ha Yoo reports financial support was provided by 10.13039/501100003653Korea National Institute of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD., Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations., Results: Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888)., Conclusions: The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1129/coif). C.K.R. serves as an unpaid editorial board member of Journal of Thoracic Disease. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Preserved ratio impaired spirometry (PRISm) is a heterogeneous disease entity. Limited data are available regarding its prevalence, clinical course, or prognosis. We aimed to evaluate the longitudinal clinical course of patients with PRISm compared with chronic obstructive pulmonary disease (COPD)., Methods: A retrospective study enrolled PRISm and COPD patients who underwent chest computed tomography and longitudinal pulmonary function tests between January 2013 and December 2020. We compared the incidence of acute exacerbations and lung function changes between PRISm and COPD patients., Results: Of the 623 patients, 40 and 583 had PRISm and COPD, respectively. Compared to COPD patients, PRISm patients were younger, more likely to be female and have a history of tuberculosis, and less likely to be smokers. They also had less severe comorbidities, lower forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (D LCO ). The clinical course was not significantly different between the PRISm and COPD patients in terms of the risk of moderate-to-severe acute exacerbations or proportion of frequent exacerbators. During follow-up, PRISm patients had a significantly slower annual decline of forced expiratory volume in 1 second, FVC, and DL CO than COPD patients., Conclusion: PRISm patients had no significant difference in the risk of acute exacerbations, but a significantly slower decline of lung function during longitudinal follow-up, compared with COPD patients., Competing Interests: The authors report no potential conflicts of interest in this work., (© 2024 Yoon et al.)

This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

A weak correlation between diffusing capacity of the lung for carbon monoxide (DL CO ) and emphysema has been reported. This study investigated whether impaired DL CO in chronic obstructive pulmonary disease (COPD) is associated with increased risk of acute exacerbation independent of the presence or extent of emphysema. This retrospective cohort study included patients with COPD between January 2004 and December 2019. The participants were divided into four groups based on visually detected emphysema and impaired DL CO . Among 597 patients with COPD, 8.5% had no emphysema and impaired DL CO whereas 36.3% had emphysema without impaired DL CO . Among the four groups, patients with impaired DL CO and emphysema showed a higher risk of moderate-to-severe or severe exacerbation than those with normal DL CO . Impaired DL CO was an independent risk factor for severe exacerbation (hazard ratio, 1.524 [95% confidence interval 1.121-2.072]), whereas the presence of emphysema was not. The risk of moderate-to-severe or severe exacerbation increases with the severity of impaired DL CO . After propensity-score matching for the extent of emphysema, impaired DL CO was significantly associated with a higher risk of moderate-to-severe (p = 0.041) or severe exacerbation (p = 0.020). In patients with COPD and heterogeneous parenchymal abnormalities, DL CO can be considered an independent biomarker of acute exacerbation., (© 2024. The Author(s).)

Background: Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients., Methods: Our cross-sectional study evaluated Choi's, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV 1 ) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD)., Results: In the eligible 2,180 COPD patients, lower predicted values of FEV 1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations. GLI-2012 equation resulted in a lower proportion of patients being classified as FEV 1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV 1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV 1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD)., Conclusion: GLI-2012 reference equation may not accurately reflect FEV 1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV 1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background and Objectives: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction., Methods: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV 1 )/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV 1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC)., Results: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV 1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted β-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL., Conclusion: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV 1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction., (© 2024. The Author(s).)

Background: Sarcopenia is a risk factor for pneumonia in the elderly, and the timed up-and-go test (TUG) can be used as a screening tool for sarcopenia in this population. This study aimed to evaluate the association between TUG test results and future pneumonia or ventilator care., Materials and Methods: From the National Health Insurance Service-Senior Cohort database, we identified 19,804 people without neurological diseases who underwent the TUG test in the National Screening Program for Transitional Ages at the age of 66 years during 2007-2008. Gait abnormality was defined as taking 10 s or longer to perform the TUG test. Pneumonia occurrence was defined using the International Classification of Diseases 10th Revision (ICD-10) code for pneumonia (J12-J18, J69), and ventilator care was defined by procedure codes (M5830, M5850, M5867, M5858, M5860, M5859) according to the Healthcare Common Procedure Coding system codes from 2007 to 2015., Results: The mean follow-up period was 7.4 years (standard error, SE 0.02). The incidence rates of pneumonia in the normal and slow TUG groups were 38 and 39.5/1000 person-years, respectively. The slow TUG group did not show a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.042; 95% confidence interval [95% CI], 0.988-1.107]). Regarding ventilator care, the incidence was 4.7 and 5.2 cases per 1,000 person-years in the normal and slow TUG groups, respectively. Slow TUG groups also did not show an increased risk of ventilator occurrence (aHR, 1.136, [95% CI = 0.947-1.363])., Conclusion: The TUG test result was not associated with future pneumonia or ventilator care and may not be useful for predicting pneumonia in community-dwelling elderly individuals. Further studies are needed to identify additional functional tools for sarcopenia associated with future pneumonia occurrences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study presents a preliminary exploration of thermally oxidized TaOx-based memristors and their potential as artificial synapses. Unlike the 10-min annealed devices, which display instability due to current overshoots, the 5-min annealed device exhibits stable resistive switching, retention, and endurance characteristics. Moreover, our memristor showcases synaptic behaviors encompassing potentiation, depression, spike-timing-dependent plasticity, and excitatory postsynaptic currents. This synaptic emulation holds tremendous promise for applications in neuromorphic computing, offering the opportunity to replicate the adaptive learning principles observed in biological synapses. In addition, we evaluate the device's suitability for pattern recognition within a neural network using the modified National Institute of Standards and Technology dataset. Our assessment reveals that the Pt/TaOx/Ta memristor with an oxidized insulator achieves outstanding potential manifested by an accuracy of 93.25% for the identical pulse scheme and an impressive accuracy of 95.42% for the incremental pulse scheme., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Although vertical configurations for high-density storage require challenging process steps, such as etching high aspect ratios and atomic layer deposition (ALD), they are more affordable with a relatively simple lithography process and have been employed in many studies. Herein, the potential of memristors with CMOS-compatible 3D vertical stacked structures of Pt/Ti/HfO x /TiN-NCs/HfO x /TiN is examined for use in neuromorphic systems. The electrical characteristics (including I - V properties, retention, and endurance) were investigated for both planar single cells and vertical resistive random-access memory (VRRAM) cells at each layer, demonstrating their outstanding non-volatile memory capabilities. In addition, various synaptic functions (including potentiation and depression) under different pulse schemes, excitatory postsynaptic current (EPSC), and spike-timing-dependent plasticity (STDP) were investigated. In pattern recognition simulations, an improved recognition rate was achieved by the linearly changing conductance, which was enhanced by the incremental pulse scheme. The achieved results demonstrated the feasibility of employing VRRAM with TiN nanocrystals in neuromorphic systems that resemble the human brain.

Nasogastric tube feeding is often used to provide optimal nutrition and hydration in patients with aspiration pneumonia. However, evidence regarding radiologic indicators for successful nasogastric tube weaning is lacking. We investigated whether thoracic skeletal muscle assessment can be useful for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia. This longitudinal, observational study included subjects with aspiration pneumonia who underwent a videofluoroscopic swallowing study (VFSS) and chest computed tomography (CT) in Boramae Medical Center, from January 2012 to December 2019. We estimated the area under the receiver operating characteristics curve (AUC) to evaluate the predictive performance of skeletal muscle and visceral fat parameters and VFSS results for successful weaning from nasogastric tube feeding. A board-certified radiologist measured muscle and fat areas. Muscle and fat volumes were segmented and measured using an externally validated convolutional neural network model. Among the 146 included patients, nasogastric tube feeding was successfully transitioned to oral feeding in 46.6%. After adjusting for covariables related to successful weaning, skeletal muscle areas, indices, and volume indices were positively associated with successful nasogastric tube weaning. Although VFSS results and skeletal muscle parameters alone showed suboptimal performance for predicting successful weaning, a prediction model combining skeletal muscle index at the T4 level and VFSS results improved the prediction performance to an acceptable level (AUC ≥ 0.7). Skeletal muscle index measured at the T4 level may be a useful supplementary indicator for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3-5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17-24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39-53%) and 43% (95% CI 31-55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors., (© 2023. The Author(s).)

BACKGROUND This study aimed to compare the incidence of brain-dead (BD) donors and potential brain-dead (PBD) donors before vs after the introduction of intensivists. MATERIAL AND METHODS This longitudinal retrospective study was performed between January 2012 and December 2020 at Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Four dedicated intensivists were introduced in January 2016. The periods before and after introduction of the intensivists were defined as the pre-introduction period (2012-2015) and post-introduction period (2016-2020), respectively. RESULTS During the study period, there were 2872 discharges in the Intensive Care Unit, of which there were a total of 113 PBD (3.93%) and 36 BD (1.25%) donors. The number of PBD and BD donors increased in the post-introduction period compared in the pre-introduction period (PBD, 47.84 vs 27.14 per 1000 discharges; BD, 13.59 vs 11.03 per 1000 discharges). Poisson regression analysis showed the annual incidence rate of PBD donors significantly increased post-introduction (PBD, 27.53% vs 48.11%, P=0.044), while those of BD donors were similar between the 2 groups (BD, 11.41% vs 13.9%; P=0.743). The annual incidence rate of the total number of organ donations, multi-organ donations (>3 organs), and donation of organs (heart, lung, and kidney) increased in the post-introduction period compared to that in the pre-introduction period. CONCLUSIONS Our findings suggest a beneficial role of a dedicated intensivist, not only in improving actual organ donation and discovering PBD donors, but also in affecting the yield of the heart and lung transplantation in actual organ donation compared to donors without a dedicated intensivist.

In this work, we analyze a resistive switching random access memory (RRAM) device with the metal-insulator-metal structure of Al/αTiO x /Al. The transport mechanism of our RRAM device is trap-controlled space-charge limited conduction, which does not change during the endurance test. As the number of resistive switching (RS) cycles increases, the current in the low-resistance state (LRS) does not change significantly. In contrast, degradation in the high-resistance state (HRS) is noticeably evident. According to the RS cycle, the current shift fits well with the stretched-exponential equation. The normalized noise power spectral density ( S i / I 2 ) measured in the HRS is an order of magnitude higher than that in the LRS owing to the difference in the degree of trap occupancy, which is responsible for the transition of resistance states. During the consecutive RS, the S i / I 2 in the HRS rapidly decreases for approximately 100 cycles and then saturates. In contrast, in the LRS, the S i / I 2 does not change significantly. Here we propose a model associated with the endurance degradation of the experimental device, and the model is verified with a 1/f noise measurement.

Background: Limited data are available concerning cardiovascular risk with respect to adjunctive corticosteroid use in patients with pneumonia. We aimed to assess the associations between systemic corticosteroid use and the occurrence of major adverse cardiovascular events (MACEs) in patients hospitalized for pneumonia., Methods: Among study participants enrolled via surveillance for severe acute respiratory infection from July 2016 to January 2017, the clinical course of patients with pneumonia was retrospectively investigated until December 2019. We evaluated the occurrence of in-hospital and after-discharge MACEs according to steroid use during hospitalization., Results: Of the 424 patients hospitalized for pneumonia, 118 (28.8%) received systemic corticosteroids during hospitalization. The most common reason for steroid use was acute exacerbation of chronic lung disease (75.4%). Systemic steroid use was significantly associated with an increased risk of in-hospital MACEs; it was not associated with after-discharge MACEs. The risk of in-hospital MACEs was significantly greater in patients with more comorbidities, more severe pneumonia, and a higher inflammatory marker level; moreover, it was positively associated with duration and cumulative dose of steroid treatment., Conclusion: Systemic corticosteroid use was associated with an increased risk of in-hospital MACEs in patients hospitalized for pneumonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The interim findings of this paper were presented at the KATRD International Conference 2020 as an oral presentation on November 13, 2020., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV 1 /FVC decline rate in the Korean general population and to identify whether rapid FEV 1 /FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality., Methods: We evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV 1 /FVC decline rate, the most negative FEV 1 /FVC change (1 st quartile of annual FEV 1 /FVC decline rate) was classified as rapid FEV 1 /FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV 1 /FVC decline., Results: The annual FEV 1 /FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV 1 /FVC decline than in those with non-rapid FEV 1 /FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV 1 /FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105-1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089-1.680)., Conclusion: The annual FEV 1 /FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV 1 /FVC decliners., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: The Rome proposal provides an objective assessment tool for severity of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) but requires validation., Objectives: We aimed to evaluate the predictive performance of the Rome proposal in patients with AE-COPD., Design: This observational study assessed the patients who visited the emergency room (ER) or were hospitalized due to AE-COPD between January 2010 and December 2020., Methods: We compared the performance of the Rome Proposal with that of the DECAF score or GesEPOC 2021 criteria in predicting intensive care unit (ICU) admission, need for non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), and in-hospital mortality., Results: A total of 740 events of ER visit or hospitalization due to AE-COPD were reviewed and classified into mild (30.9%), moderate (58.6%), or severe (10.4%) group according to the Rome proposal. The severe group had a higher rate of ICU admission, required more NIV or IMV, and had a higher in-hospital mortality than the mild and moderate groups. The predictive performance of the Rome proposal was significantly better for ICU admission [area under the receiver operating characteristic curve (AU-ROC) = 0.850 versus 0.736, p  = 0.004] and need for NIV or IMV (AU-ROC = 0.870 versus 0.770, p  = 0.004) than that of the GesEPOC 2021 criteria but better than that of the DECAF score only in female patients. There was no significant difference in predicting the in-hospital mortality between the Rome proposal and DECAF score or GesEPOC 2021 criteria., Conclusion: External validation of the Rome Proposal in Korean patients demonstrated excellent performance for ICU admission and need for NIV or IMV and an acceptable performance for in-hospital mortality.

Background: Comorbidities of chronic obstructive pulmonary disease (COPD) influence clinical characteristics and prognosis., Objectives: This study compared the clinical characteristics and exacerbation rate of COPD according to the presence of depression or anxiety., Design: This study used data from The Korea COPD Subgroup Study (KOCOSS) cohort, a nationwide prospective cohort from 54 medical centers, between April 2012 and 2019., Methods: Depression and anxiety were diagnosed with the Beck Depression Inventory and Beck Anxiety Inventory. Negative binomial regression analysis was performed to analyze the frequency of exacerbations in depressed patients and anxiety. Differences in lung function trajectory according to presence of depression/anxiety were analyzed using a linear mixed model., Results: In all, 2147 patients were enrolled. Depressed patients or anxiety had lower lung function, higher modified Medical Research Council (mMRC) grade, St. George Respiratory Questionnaire (SGRQ) score, and COPD assessment test score, and higher rates of exacerbation in the past year than those without depression/anxiety. Depressed patients had a higher frequency of moderate to severe exacerbations [Incidence Rate Ratio (IRR): 1.57, CI: 1.17-2.11, p  = 0.002] and those with anxiety had higher frequencies of moderate to severe (IRR: 1.52, CI: 1.03-2.27, p  = 0.038) and severe exacerbations (IRR: 2.13, CI: 1.09-4.15, p  = 0.025) during 1-year follow-up compared to those without these comorbidities. The differences in the change in annual forced expiratory volume in 1 seconds (FEV 1 ) over 3 years according to the presence of depression or anxiety were not statistically significant., Conclusion: Depressed and anxious patients showed increased respiratory symptoms and exacerbation rate as well as reduced health-related quality of life, whereas there were no significant differences in changes in lung function between groups with and without depression/anxiety.

Background: Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19., Methods: We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts., Results: Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rank p -value < 0.001). In the multivariable Cox regression analysis, leukopoenia group was significantly associated with a lower risk of the composite poor outcome compared to normal WBC group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.14-0.76, p -value = 0.009) and leukocytosis group (aHR = 0.30, 95% CI = 0.12-0.78, p -value = 0.013). There was no significant difference in aHR for composite poor outcome between leukocytosis and normal WBC group., Conclusion: Leukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation.KEY MESSAGESIn severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis.Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

Bisphenol A is an environmental endocrine disruptor that has similar functions to estrogen in humans. However, few studies have investigated pulmonary inflammation induced by BPA, and the effect of Athyrium yokoscense extract on this inflammatory response is unknown. In this study, we investigated this effect in A549 human alveolar epithelial cells. BPA at concentrations higher than 100 µM were cytotoxic to A549 cells at 24 and 48 h after treatment; however, AYE (100 µg/mL) had a protective effect against BPA-induced cytotoxicity. AYE also inhibited the generation of intracellular reactive oxygen species, expressions of cyclooxygenase-2 and extracellular signal-regulated kinase1/2 proteins, activities of phospholipase A 2 , COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells, and proinflammatory mediators including prostaglandin E 2 , tumor necrosis factor-α, and interleukin-6 induced by BPA in A549 cells. This study demonstrated that BPA, which induces chronic lung disease, causes oxidative stress and inflammatory response in lung epithelial cell line, and found that AYE reduces BPA-induced oxidative stress and inflammatory response by down-regulating the Erk1/2 and NF-κB pathways., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis., Methods: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994., Findings: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group., Interpretation: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis., Funding: Korea Disease Control and Prevention Agency, South Korea., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Only limited data are available regarding the effects of bronchiectasis on the clinical course of asthma., Objective: This study evaluated longitudinal clinical outcomes according to bronchiectasis status in patients with asthma., Methods: This retrospective study included patients with asthma who underwent chest computed tomography and pulmonary function tests between January 2013 and December 2019. The annual incidence of episodes of moderate-to-severe acute clinical deterioration (exacerbations) and longitudinal changes in lung function were evaluated., Results: Of 667 patients with asthma, 251 had bronchiectasis. Patients with bronchiectasis had significantly more history of tuberculosis and nontuberculous mycobacterial lung disease, and lower forced expiratory volume in 1 second and forced vital capacity, compared with patients without bronchiectasis, although there was no difference in smoking intensity and inhaled corticosteroid treatment. Bronchiectasis was significantly associated with higher annual rates of severe and moderate-to-severe acute exacerbations; it was also associated with greater risk of acute exacerbation during follow-up. The severity and progression of bronchiectasis were independent risk factors for acute exacerbation. There were no significant differences in annual decline of lung function according to bronchiectasis status or bronchiectasis progression., Conclusions: In patients with asthma, the presence and progression of bronchiectasis were significantly associated with increased risk of moderate-to-severe acute exacerbation, but they were not associated with longitudinal changes in lung function., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Few studies have reported the association between the radiographic characteristics and the development of pneumonia in patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids (ICSs). Our study aimed to assess the effect of radiographic phenotypes on the risk of pneumonia in patients treated with ICSs., Patients and Methods: This study retrospectively analysed all patients with COPD treated with ICSs in a subset of the Korea Chronic Obstructive Pulmonary Disorders Subgroup Study registry between January 2017 and December 2019. The association between radiographic phenotypes including the presence and severity of emphysema, airway wall thickening, or bronchiectasis on chest computed tomography were determined visually/qualitatively and the risk of pneumonia was analyzed using the Cox regression model., Results: Among the 90 patients with COPD treated with ICSs, 41 experienced pneumonia more than once during the median follow-up of 29 (interquartile range, 8-35) months. In univariate Cox regression analysis, older age, longer use of ICSs, use of fluticasone propionate or metered dose inhaler, and severe exacerbation events increased the risk of pneumonia. In multivariate analysis, the presence of emphysema (adjusted hazard ratio [aHR]=3.73, P=0.033), severity measured using the visual sum score (mild-to-moderate, aHR=8.58, P=0.016; severe, aHR=3.58, P=0.042), Goddard sum score (mild-to-moderate, aHR=3.31, P=0.058; severe, aHR=5.38, P=0.014), and the upper lobe distribution of emphysema (aHR=3.76, P=0.032) were associated with a higher risk of pneumonia. Subtypes of centrilobular and panlobular emphysema had a higher risk of pneumonia compared with paraseptal emphysema (aHR=3.98, P=0.033; HR=3.91, P=0.041 vs HR=2.74, P=0.304). The presence of bronchiectasis (aHR=2.41, P=0.02) and emphysema/bronchiectasis overlap phenotype (aHR=2.19, P=0.053) on chest CT was a risk factor for pneumonia in this population. However, severity of bronchiectasis and the presence or severity of bronchial wall thickening according to the visual sum score were not associated with the risk of pneumonia., Conclusion: Among patients with COPD treated with ICSs, radiographic phenotypes including the presence of emphysema, bronchiectasis or emphysema/bronchiectasis overlap phenotype, severity with emphysema, subtypes of centrilobular or panlobular emphysema, and upper lobe distribution of emphysema may help predict the risk of pneumonia., Competing Interests: All authors report no conflicts of interest in relation to this work., (© 2022 Lee et al.)

Background: The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted., Methods: This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited., Discussion: This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB., Trial Registration: ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020., (© 2022. The Author(s).)

Background: Death by suicide is a major public health problem. To provide multidisciplinary support to patients who attempted suicide, emergency department (ED)-based psychiatric screening and intervention programs were offered. We traced the long-term survival outcome of patients visiting the ED after suicide attempts using the national death certificate registration database., Methods: A retrospective observational study was conducted using a database of patients from "Psychiatric Crisis Response Centers" (PCRC) of 27 EDs between January 2013 and August 2015. Patients who visited the ED after attempting suicide were screened and interviewed by social workers from the PCRC. The database was merged with the national death certificate database to trace the death and cause of death of the patients until December 2018. The characteristics and outcomes were compared based on the patient's compliance with the follow-up case management program., Results: Of the 12,544 interviewed patients, the data of 9,587 patients were successfully matched with data from the death certificate database. Death by suicide was higher in the noncompliance group (4.5% vs. 12.4%, P < 0.001); however, death caused by factors other than suicide did not differ between groups (4.8% vs. 4.9%, P = 0.906)., Conclusion: Suicide resulted in a lower long-term mortality rate among patients who complied with the follow-up case management session in the ED-based brief psychiatric intervention and follow-up program., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer., Research Question: Is accelerated lung function decline associated with the development of lung cancer?, Study Design and Methods: A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV 1 > 60 mL per year were defined as rapid FEV 1 decliners. The relationship between lung cancer and rapid FEV 1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV 1 /FVC, and WBC count., Results: Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV 1 decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged ≥ 45 years and those with ≥ 30 pack-years of smoking, low baseline FEV 1 /FVC, low forced expiratory flow between 25% and 75% of vital capacity, rapid FEV 1 decline, and increased WBC count. Rapid FEV 1 decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95% CI, 1.28-4.28; P = .006). Time-dependent net reclassification improvement showed a benefit of FEV 1 decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95% CI, 0.00-0.64]; continuous, 0.83 [95% CI, 0.14-1.25])., Interpretation: The FEV 1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV 1 decline warrant lung cancer assessment or screening., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Gaseous pollutants, including nitrogen oxides, pose a severe threat to ecosystems and human health; therefore, developing reliable gas-sensing systems to detect them is becoming increasingly important. Among the various options, metal-oxide-based gas sensors have attracted attention due to their capability for real-time monitoring and large response. In particular, in the field of materials science, there has been extensive research into controlling the morphological properties of metal oxides. However, these approaches have limitations in terms of controlling the response, sensitivity, and selectivity after the sensing material is deposited. In this study, we propose a novel method to improve the gas-sensing performance by utilizing the remnant polarization of ferroelectric thin-film transistor (FeTFT) gas sensors. The proposed FeTFT gas sensor has IGZO and HZO as the conducting channel and ferroelectric layer, respectively. It is demonstrated that the response and sensitivity of FeTFT gas sensors can be modulated by engineering the polarization of the ferroelectric layer. The amount of reaction sites in IGZO, including electrons and oxygen vacancy-induced negatively charged oxygen, is changed depending on upward and downward polarization. The results of this study provide an essential foundation for further development of gas sensors with tunable sensing properties.

Background: Flexible bronchoscopy is widely used to diagnose and treat various respiratory diseases. However, caution is warranted for post-bronchoscopy adverse events. Although desaturation frequently occurs during bronchoscopy, its clinical impact and the optimal oxygen saturation level during the procedure remain unclear. This study aimed to investigate whether the percutaneous oxygen saturation (SpO 2 ) level during bronchoscopy is associated with the development of post-bronchoscopy respiratory adverse events., Methods: In this single-center retrospective cohort study conducted from March 2020 to February 2021, 569 patients were classified into high or low oxygen saturation groups based on the SpO 2 level during bronchoscopy. The primary outcome was post-bronchoscopy respiratory adverse events, and secondary outcomes were other post-bronchoscopy adverse events and clinical outcomes., Results: Among 569 patients, 458 and 111 patients were classified into the high oxygen saturation (SpO 2  > 96%) and low oxygen saturation (SpO 2  ≤ 94%) groups, respectively. After propensity score matching, the low oxygen saturation group had more post-bronchoscopy respiratory and febrile adverse events than the high oxygen saturation group. In the multivariable regression analysis, low SpO 2 level during bronchoscopy was an independent risk factor for post-bronchoscopy respiratory adverse events (odds ratio = 3.16 [95% confidence interval 1.37-7.30]). In the low oxygen saturation group, the high-risk subgroups for post-bronchoscopy respiratory adverse events were the elderly, women, current smokers, and patients with chronic obstructive pulmonary disease or acute decompensated heart failure before bronchoscopy. There was no significant difference in the length of hospital stay, intensive care unit admission, or mortality between the high and low oxygen saturation groups., Conclusions: Close monitoring is recommended for patients with SpO 2  ≤ 94% during bronchoscopy due to the increased risk of respiratory adverse events after the procedure., (© 2022. The Author(s).)

Background/aims: Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF., Methods: This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)., Results: The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was -6.56% (95% confidence interval [CI], -9.26 to -3.87) per year before, but -4.43% (95% CI, -5.87 to -3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was -4.96% (95% CI, -6.82 to -3.09) per year before, but -1.79% (95% CI, -2.75 to -0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II-III than in the stage I group., Conclusion: The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

The appropriate strategy for enteral feeding remains a matter of debate. We hypothesized that continuous enteral feeding would result in higher rates of achieving target nutrition during the first 7 days compared with intermittent enteral feeding. We conducted an unblinded, single-center, parallel-group, randomized controlled trial involving adult patients admitted to the medical intensive care unit who required mechanical ventilation to determine the efficacy and safety of continuous enteral feeding for critically ill patients compared with intermittent enteral feeding. The primary endpoint was the achievement of ≥80% of the target nutrition requirement during the first 7 days after starting enteral feeding. A total of 99 patients were included in the modified intention-to-treat analysis (intermittent enteral feeding group, n = 49; continuous enteral feeding group, n = 50). The intermittent enteral feeding group and continuous enteral feeding group received 227 days and 226 days of enteral feeding, respectively. The achievement of ≥80% of the target nutrition requirement occurred significantly more frequently in the continuous enteral feeding group than in the intermittent enteral feeding group (65.0% versus 52.4%, respectively; relative risk, 1.24; 95% confidence interval, 1.06-1.45; p = 0.008). For patients undergoing mechanical ventilation, continuous enteral feeding significantly improved the achievement of target nutrition requirements.

Degree of expression of programmed death-ligand 1 (PD-L1) is related with Immune check point inhibitors (ICIs) response but it needs sufficient tumor tissue. There is unmet need for easily accessible and prognostic peripheral blood (PB) biomarkers. We investigated the application of serum peripheral lymphocyte count (PLC) as a predictive PB biomarker for ICI response in patients with NSCLC. We conducted a retrospective study and reviewed the patients with NSCLC who were treated with ICIs from April 1, 2016, to March 31, 2019. The PLC before and after 1 month of immunotherapy was collected. We evaluated the association between PLC and progression-free survival (PFS), overall survival (OS) and adverse events. A total of 231 patients were treated with ICIs for NSCLC. The median follow-up period was 4.7 months and the disease progressed in 138 patients (59.7%). Compared with the lowest quartile (Q1: the lowest 25%), the highest quartile (Q4: the highest 25%) of post-treatment PLC showed a significantly higher PFS (HR 0.28, 95% CI 0.16-0.52) and OS (HR 0.35, 95% CI 0.19-0.65) in the adjusted model. An association between adverse events and PLC was not observed. We revealed that an increased pre- and post-treatment PLC was associated with favorable PFS and OS with NSCLC patients treated with ICIs. PLC could be a helpful for ICI responses in NSCLC., (© 2022. The Author(s).)

Background: Rapid forced expiratory volume in 1 s (FEV1) decliners have been considered a unique subgroup of patients with chronic obstructive pulmonary disease (COPD). Rapid FEV1 decline manifests early and is associated with poor prognosis. This necessitates the pre-emptive identification of risk factors for rapid FEV1 decline., Objectives: We aimed to determine the risk factors and clinical outcomes in patients with COPD., Methods: This longitudinal, observational study was based on the Korea COPD Subgroup Study cohort (NCT02800499) from January 2012 to December 2019 across 54 medical centers in South Korea. Eligible patients were followed up for 3 years with serial spirometric tests. We calculated the annualized percentage change in FEV1 from baseline. Rapid decliners were defined as the quartile of patients with the highest annualized percentage FEV1 decline., Results: Of the 518 patients, 130 were rapid decliners who lost 6.2%/year and 100 mL/year of FEV1. The multivariable logistic regression identified male sex, current smoking, blood eosinophil count <150/µL, and high forced vital capacity as the independent risk factors for rapid FEV1 decline. Among rapid decliners, the lung function deteriorated more rapidly in current smokers and patients with severe dyspnea, while triple combination therapy attenuated lung function decline in comparison with mono-bronchodilator therapy. Rapid decliners had a higher rate of severe exacerbation than nonrapid decliners (0.2/year vs. 0.1/year, p value = 0.032)., Conclusions: We identified the independent risk factors for rapid FEV1 decline. This information may assist physicians in the early detection and pertinent management of rapid decline among patients with COPD., (© 2022 S. Karger AG, Basel.)

Introduction: We aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI)., Methods: We prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects., Results: QFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its "TB2 tube". The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI., Conclusions: QFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8 + T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI., (Copyright © 2021. Published by Elsevier Ltd.)

Background/aims: We assessed the diagnostic yield of chest computed tomography (CT) as an initial diagnostic method for patients with a tuberculosis (TB) infection detected by mass screening in a country with an intermediate TB burden., Methods: A retrospective study was conducted on patients with TB infection detected by mass screening performed between January 2015 and March 2018. The patients were classified according to whether they had a chest X-ray (CXR) or CT scan as an initial diagnostic test to exclude active TB., Results: Of 542 patients with TB infection detected by mass screening, 222 and 320 were initially examined by CXR and CT, respectively; the two modalities showed no significant difference in rate of detection of patients with active TB (0.9% and 2.5%, respectively; p = 0.110). However, chest CT was associated with further invasive tests using bronchoscopy and respiratory specimens, and significantly increased the frequency of hospital visits., Conclusion: Chest CT was not supported as an initial diagnostic method to rule out active TB in patients with a TB infection detected by mass screening in a country with an intermediate TB burden.

Background Determining the activity of pulmonary tuberculosis on chest radiographs is difficult. Purpose To develop a deep learning model to identify active pulmonary tuberculosis on chest radiographs. Materials and Methods Chest radiographs were retrospectively gathered from a multicenter consecutive cohort with pulmonary tuberculosis who were successfully treated between 2011 and 2017, along with normal radiographs to enrich a negative class. The pretreatment and posttreatment radiographs were labeled as positive and negative classes, respectively. A neural network was trained with those radiographs to calculate the probability of active versus healed tuberculosis. A single-center consecutive cohort (test set 1; 89 patients, 148 radiographs) and data from one multicenter randomized controlled trial (test set 2; 366 patients, 3774 radiographs) were used to test the model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model and of the four expert readers. Results In total, 6654 pre- and posttreatment radiographs from 3327 patients (mean age ± standard deviation, 55 years ± 19; 1884 men) with pulmonary tuberculosis and 3182 normal radiographs from as many patients (mean age, 53 years ± 14; 1629 men) were gathered. For test set 1, the model showed a higher AUC (0.83; 95% CI: 0.73, 0.89) than one pulmonologist (0.69; 95% CI: 0.61, 0.76; P < .001) and performed similarly to the other readers (AUC, 0.79-0.80; P = .14-.23). For 200 randomly selected radiographs from test set 2, the model had a higher AUC (0.84) than the pulmonologists (0.71 and 0.74; P < .001 and .01, respectively) and performed similarly to the radiologists (0.79 and 0.80; P = .08 and .06, respectively). The model output increased by 0.30 on average with a higher degree of smear positivity (95% CI: 0.20, 0.39; P < .001) and decreased during treatment (baseline, 3 months, and 6 months: 0.85, 0.51, and 0.26, respectively). Conclusion A deep learning model performed similarly to radiologists for accurately determining the activity of pulmonary tuberculosis on chest radiographs; it also was able to follow posttreatment changes. © RSNA, 2021 Online supplemental material is available for this article.

Purpose: To investigate the incidence of tuberculosis (TB) in healthcare workers (HCWs) with positive interferon-gamma release assay (IGRA) results based on chest X-ray (CXR) and CT findings and determine the role of imaging in the diagnosis of TB., Materials and Methods: Among 1976 hospital personnel screened for TB using IGRA, IGRA-positive subjects were retrospectively investigated. Clustered nodular and/or linear streaky opacities in the upper lung zone were considered positive on CXR. The CT findings were classified as active, indeterminate, inactive, or normal. The active or indeterminate class was considered CT-positive., Results: IGRA was positive in 255 subjects (12.9%). CXR and CT were performed in 249 (99.2%) and 113 subjects (45.0%), respectively. CXR- and CT-positive findings were found in 7 of 249 (2.8%) and 9 of 113 (8.0%) patients, respectively. Among the nine CT-positive subjects, active and indeterminate TB findings were found in 6 (5.3%) and 3 (2.7%) patients, respectively. Microbiological tests, including acid-fast bacilli staining, culture, and polymerase chain reaction for TB, were negative in all nine CT-positive subjects. Empirical anti-TB medications were administered to 9 CT-positive subjects, and 3 of these nine subjects were CXR-negative for pulmonary TB., Conclusion: CT helped diagnose asymptomatic TB in IGRA-positive HCWs., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)

Background: Despite the proven benefits of dexamethasone in hospitalized coronavirus disease 2019 (COVID-19) patients, the optimum time for the administration of dexamethasone is unknown. We investigated the progression of COVID-19 pneumonia based on the timing of dexamethasone administration., Methods: A single-center, retrospective cohort study based on medical record reviews was conducted between June 10 and September 21, 2020. We compared the risk of severe COVID-19, defined as the use of a high-flow nasal cannula or a mechanical ventilator, between groups that received dexamethasone either within 24 hours of hypoxemia (early dexamethasone group) or 24 hours after hypoxemia (late dexamethasone group). Hypoxemia was defined as room-air SpO2 <90%., Results: Among 59 patients treated with dexamethasone for COVID-19 pneumonia, 30 were in the early dexamethasone group and 29 were in the late dexamethasone group. There was no significant difference in baseline characteristics, the time interval from symptom onset to diagnosis or hospitalization, or the use of antiviral or antibacterial agents between the two groups. The early dexamethasone group showed a significantly lower rate of severe COVID-19 compared to the control group (75.9% vs. 40.0%, p=0.012). Further, the early dexamethasone group showed a significantly shorter total duration of oxygen supplementation (10.45 days vs. 21.61 days, p=0.003) and length of stay in the hospital (19.76 days vs. 27.21 days, p=0.013). However, extracorporeal membrane oxygenation and in-hospital mortality rates were not significantly different between the two groups., Conclusion: Early administration of dexamethasone may prevent the progression of COVID-19 to a severe disease, without increased mortality.

Background: The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes., Methods: We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD)., Results: In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV₁ change in patients with erosive reflux esophagitis was -51.8 mL/yr, while it decreased by 46.8 mL/yr in controls ( P = 0.270). The adjusted annual FVC decline was similar between the two groups (-55.8 vs. -50.5 mL/yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups., Conclusion: In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV₁ or FVC., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive., Methods: To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR)., Results: We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10 -7 ), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10 -8 . The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A , a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (β, -4.627; 95% CI, -8.768 to -0.486; p=0.029)., Conclusions: The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Although a majority of coronavirus disease 2019 (COVID-19) cases were characterized as mild, data assessing the development of pneumonia in mild COVID-19 patients are limited. We aimed to examine the effect of pneumonia development on the clinical course of mild COVID-19 in hospitalized patients., Methods: A retrospective cohort study was conducted via medical record review between February 25, 2020 and April 11, 2020 at a single center. The impact of pneumonia development on the time to viral clearance in mild COVID-19 patients was evaluated. Risk factors associated with the development of pneumonia were also identified., Results: Chest radiographs revealed the development of pneumonia in 26.8% of mild COVID-19 patients. The time to pneumonia development was a median of 8.0 days from the onset of symptoms and 3.5 days after hospital admission. A multivariate analysis for predicting pneumonia development identified age ≥ 65 years (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.14 to 8.73), cough (OR, 2.18; 95% CI, 1.29 to 3.68), dyspnea (OR, 3.58; 95% CI, 1.10 to 11.69), and diarrhea (OR, 2.69; 95% CI, 1.51 to 4.78) as significant variables. The time to negative conversion was longer in mild COVID-19 patients who developed pneumonia (23.6 days vs. 18.4 days, p = 0.003). In Kaplan-Meier estimation and multivariate Cox regression analyses, newly developed pneumonia was significantly related with delayed time to negative conversion (log-rank test, p = 0.02; hazard ratio, 2.90; 95% CI, 1.06 to 7.97)., Conclusion: The development of pneumonia delayed viral clearance in patients with mild COVID-19. Elderly patients or those suffering from diarrhea should be closely monitored, given the increased risk of developing pneumonia.

Background: The presence and progression of interstitial lung abnormalities (ILAs) is known to be associated with a decline of lung function and increased risk of mortality., Research Question: We aimed to elucidate the clinical course according to ILAs in patients with COPD., Study Design and Methods: A retrospective study was conducted between January 2013 and December 2018 of COPD patients who underwent chest CT imaging and longitudinal pulmonary function tests. We evaluated radiologic findings, history of acute exacerbations of COPD, and lung function changes during the longitudinal follow-up., Results: Of 363 patients with COPD, 44 and 103 patients had equivocal and definite ILAs, respectively. Patients with ILAs were significantly older and had lower FEV 1 and FVC than patients without ILAs. During the mean follow-up period of 5.2 years, ILAs were associated significantly with the annual incidence of moderate to severe acute exacerbation of COPD (β ± SD, 0.38 ± 0.12; P = .002) and with the risk of frequent exacerbation (adjusted OR, 2.03; P = .045). Patients with progressive ILAs showed a significantly higher rate of annual decline in FEV 1 and FVC than those showing no change in, or improved, ILAs., Interpretation: ILAs were associated significantly with moderate to severe acute exacerbation in patients with COPD, and the progression of ILAs was associated with an accelerated decline in lung function., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)