Publications by authors named "Sang Haak Lee"

126 Publications

A pilot investigation of e-cigarette use and smoking behaviour among patients with chronic airway disease or respiratory symptoms.

Clin Respir J 2021 Sep 6. Epub 2021 Sep 6.

Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.

Background: This pilot study aimed to investigate the current status of e-cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health.

Methods: A cross-sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study.

Results: A total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health-related reasons. When comparing exclusive ECs users and dual users, St. George's respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively.

Conclusion: Most of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort.
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http://dx.doi.org/10.1111/crj.13445DOI Listing
September 2021

Reflux esophagitis in patients with chronic obstructive pulmonary disease.

Medicine (Baltimore) 2021 Aug;100(34):e27091

Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Abstract: The relationship between chronic obstructive pulmonary disease (COPD) and reflux esophagitis (RE) was controversial. We investigated the factors influencing RE development in patients with COPD and evaluated the association between RE and AECOPD.Patients with COPD who underwent esophagogastroduodenoscopy from January 2003 to December 2013 in St. Paul's Hospital, the Catholic University of Korea (Seoul, Korea) were enrolled retrospectively. The grade of RE was based on the Los Angeles classification and minimal change esophagitis. Body mass index, smoking history, medical history, AECOPD, pulmonary function test data, endoscopic findings, and comorbidities were reviewed.Of a total of 218 patients with COPD, 111 (50.9%) were diagnosed with RE. None of age, sex, smoking history, or the severity of airflow limitation was associated with RE. AECOPD was not related to either the presence or severity of RE. There was no significant correlation between RE grade by Los Angeles classification and severity of airflow limitation (P = .625). Those who had RE used theophylline (P = .003) and long-acting muscarinic antagonists (P = .026) significantly more often than did controls. The use of theophylline (OR 2.05; 95% CI, 1.16-3.65, P = .014) was associated with an increased incidence of RE.The use of theophylline might increase the risk of RE in COPD patients. RE may not be associated with airflow limitation or AECOPD.
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http://dx.doi.org/10.1097/MD.0000000000027091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389875PMC
August 2021

Predictability of early changes in derived neutrophil-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

J Thorac Dis 2021 May;13(5):2824-2832

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: As association between systemic inflammation and disease progression has been suggested, early changes in neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) may have accurate predictability for prognosis in non-small cell lung cancer (NSCLC) treated with ICI therapy.

Methods: Complete blood count (CBC) was measured immediately before the first and second cycles of ICI therapy in patients with advanced NSCLC. Differences in NLR and dNLR were measured. When the increase in NLR was ≥1, the patient was classified into the increased NLR group. Similarly, when the increase in dNLR was ≥1, the patient was classified into the increased dNLR group; otherwise, they were classified into the non-increased NLR or dNLR group.

Results: A total of 89 patients was selected for evaluation. Median progression-free survival (PFS) was significantly shorter in the increased NLR group than in the non-increased NLR group (2.6 9.5 months, P<0.001). The increased dNLR group showed significantly shorter median PFS than the non-increased dNLR group (4.2 9.2 months, P=0.001). Association with PFS was analyzed using the Cox regression model. In model 1, increase ≥1 in NLR showed significant association (HR =3.085, 95% CI, 1.657-5.742, P<0.001). In model 2, increase ≥1 in dNLR showed significant association (HR =2.826, 95% CI, 1.436-5.561, P=0.003).

Conclusions: Early changes in dNLR were shown to have prognostic value in patients undergoing immunotherapy. It can be an accurate and a comprehensive biomarker for predicting ICI response.
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http://dx.doi.org/10.21037/jtd-20-3416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182547PMC
May 2021

Incidence of tuberculosis in advanced lung cancer patients treated with immune checkpoint inhibitors - A nationwide population-based cohort study.

Lung Cancer 2021 08 31;158:107-114. Epub 2021 May 31.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea. Electronic address:

Objectives: The aim of this study was to investigate the risk of TB in advanced non-small cell lung cancer (NSCLC) patients treated with Immune checkpoint inhibitors (ICI) after a platinum-based chemotherapy.

Materials And Methods: A nationwide population-based retrospective cohort study using National health insurance dataset was designed. Patients who were diagnosed as lung cancer between September 1st, 2017 and August 31st, 2018 in South Korea were selected. Among them, those with NSCLC who initiated a platinum-based chemotherapy within 3 months were finally included and followed up until December 31st, 2018. Patients who received nivolumab, pembrolizumab, and atezolizumab within study period were classified as the ICI group. Cox proportional hazard model with time-varying covariates was used to determine effects of the duration of conventional chemotherapy, ICI, and consecutive use of systemic steroid on TB.

Results: A total of 6335 patients were enrolled with 3568.7 years of total follow-up period. Among them, 899 patients underwent ICI treatment. Within the follow-up period, 15 TB cases were identified in the ICI group (incidence: 2582.5 per 100,000 person-years) and 63 TB cases were found in the conventional chemotherapy group (incidence: 2108.5 per 100,000 person-years). In a multivariable Cox proportional hazard model, treatment with ICI was not a significant risk factor for TB development (hazard ratio (HR): 1.21, 95 % confidence interval (CI): 0.45-3.26,p =  0.700). Instead, prolonged use of steroid was associated with an increased TB risk (HR: 1.91, 95 %CI: 0.89-4.08, p =  0.095), although its statistical significance was dependent on the operational definition of the effect duration. Previous TB history and older age were independent risk factors for TB disease.

Conclusion: In this real-world study, additional treatment with ICI did not increase the risk of TB in advanced NSCLC patients who underwent a cytotoxic chemotherapy. However, TB incidence in these patients was high regardless of ICI treatment.

Classifications: Systemic Treatments.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.034DOI Listing
August 2021

Clinical Characteristics and Outcome of Pathologic N0 Non-small Cell Lung Cancer Patients With False Positive Mediastinal Lymph Node Metastasis on FDG PET-CT.

In Vivo 2021 May-Jun;35(3):1829-1836

Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;

Background/aim: Preoperative fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) is a non-invasive and useful diagnostic tool to evaluate mediastinal lymph node (LN) metastasis in lung cancer. However, there are often false-positive LN cases in FDG PET-CT. This study aimed to explore the clinical characteristics and outcome of pathologic N0 non-small cell lung cancer patients with false-positive mediastinal LN on FDG PET-CT.

Patients And Methods: We enrolled 147 patients who underwent preoperative FDG PET-CT scan and mediastinal LN dissection. These patients were re-evaluated for post-operative pathologic nodal metastasis and divided into a false-positive group and a group of others.

Results: Among 40 patients diagnosed with clinical N1-3 on FDG PET-CT, 19 (47.5%) patients were pathologic N0, meaning false-positive LN by PET-CT. Preoperative absolute platelet count and platelet-lymphocyte ratio were significantly higher in patients with pathologic N0. The presence of lymphatic invasion was significantly lower in patients with pathologic N0 than in the group of others. Recurrence-free survival was significantly shorter in patients with false positive LN than in patients with true positive LN or true negative LN at the same pathologic stage.

Conclusion: Higher absolute platelet count and PLR, lower proportion of lymphatic invasion and shorter recurrence-free survival were associated with false positive mediastinal LN on preoperative FDG PET-CT.
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http://dx.doi.org/10.21873/invivo.12444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193318PMC
June 2021

Clinical significance of microbial colonization identified by initial bronchoscopy in patients with lung cancer requiring chemotherapy.

J Thorac Dis 2021 Mar;13(3):1306-1314

Division of Infectious Disease, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer.

Methods: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively.

Results: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were (n=14) and (n=6) in the surveillance culture, and (n=12) and (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 705 days, P=0.0004).

Conclusions: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.
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http://dx.doi.org/10.21037/jtd-20-2722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024789PMC
March 2021

Clinical impact of forced vital capacity on exercise performance in patients with chronic obstructive pulmonary disease.

J Thorac Dis 2021 Feb;13(2):837-846

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: Forced vital capacity (FVC) has been suggested to be a good biomarker for decreased exercise performance in patients with chronic obstructive pulmonary disease (COPD). However, as FVC is highly correlated with forced expiratory volume in 1 second (FEV), the relationship between FVC and exercise capacity should be assessed within the category of FEV1, i.e., COPD severity. However, this was not considered in previous studies. Thus, limited data are available on the association between reduced FVC and exercise capacity measured by 6-min walk distance (6MWD) based on COPD severity.

Methods: We performed a cross-sectional study using data from the Korean COPD Subgroup Study (KOCOSS) cohort. We evaluated 1,386 patients with moderate (n=895) and severe-to-very severe (n=491) COPD. Reduced FVC was defined as FVC <80% predicted and short 6MWD as <350 m. Multivariable logistic regression was used to evaluate the association between reduced FVC and short 6MWD.

Results: There were no significant differences in respiratory symptoms and quality of life between the patients with reduced FVC and those with preserved FVC. However, patients with reduced FVC had shorter 6MWD (30.5 cm in moderate and 34.5 cm in severe-to-very severe COPD) and higher BODE index scores than those with preserved FVC. The cubic spline model revealed 6MWD peaked around 93% predicted of FVC in moderate COPD, whereas FVC showed a positive association with 6MWD in severe-to-very severe COPD. Multivariable analyses showed that reduced FVC was significantly associated with short 6MWD in both moderate [adjusted odds ratio (aOR) =1.44, 95% confidence interval (CI): 1.03-2.02] and severe-to-very severe (adjusted OR =1.55, 95% CI: 1.01-2.40) COPD.

Conclusions: Reduced FVC was significantly associated with shorter 6MWD in moderate-to-very severe COPD patients, suggesting that reduced FVC might be reflective of 6MWD-measured exercise capacity in moderate-to-very severe COPD.
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http://dx.doi.org/10.21037/jtd-20-1098aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947547PMC
February 2021

The association between eosinophilic exacerbation and eosinophilic levels in stable COPD.

BMC Pulm Med 2021 Mar 2;21(1):74. Epub 2021 Mar 2.

Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Background: Blood eosinophil count may predict treatment response in patients with chronic obstructive pulmonary disease (COPD) during acute exacerbations (AE). However, the ability and thresholds of blood eosinophil counts in stable status to predict eosinophilic AECOPD have not been completely investigated.

Methods: This was a retrospective multicenter study performed January 2010 to December 2014. COPD subjects hospitalized with exacerbations, were included. Blood samples were obtained at the time of AE and stable disease at outpatient clinic before or after admission. We identified a blood eosinophil count cut-off point at stable COPD, either taken as a percentage or as absolute value, for identification of eosinophilic exacerbation.

Results: There was significant positive correlation of eosinophil counts between stable COPD and AECOPD. The best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation based on blood eosinophil count ≥ 2% was 300 cells/µL (area under the ROC curve [AUC] 0.614, P = 0.001, 39% sensitivity, 83.8% specificity). When the eosinophilic COPD exacerbation was based on blood eosinophil count ≥ 300 cells/µL, the best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation was also 300 cells/uL (AUC 0.634, P = 0.046, 45.8% sensitivity, 80.9% specificity).

Conclusions: We demonstrated association between blood eosinophil counts at stable COPD and those with AECOPD. The thresholds of blood counts at stable COPD to predict eosinophilic exacerbations was 300 cells/µL. Further and prospective studies in other populations should validate our results.
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http://dx.doi.org/10.1186/s12890-021-01443-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923497PMC
March 2021

Factors associated with discrepancy between fresh frozen and permanent biopsy from medical thoracoscopy: single center analysis of 172 medical flexible thoracoscopy cases.

J Thorac Dis 2020 Dec;12(12):7164-7173

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Frozen sections prepared during medical thoracoscopy (MT) have precise diagnostic ability in pleural pathology and may assist in decision-making before pleurodesis. The present study evaluated the diagnostic sensitivity of frozen sections from flex-rigid MT, and further evaluated clinical parameters for their association with a discrepancy between frozen sections and permanent paraffin sections.

Methods: This retrospective study evaluated 172 patients who underwent flex-rigid MT between February 2017 and November 2019 at Incheon Saint Mary's Hospital.

Results: Of the 172 patients, 85 were pathologically diagnosed with malignancy based on permanent paraffin sections. An accurate diagnosis by fresh frozen section was feasible in 88.2% of the cases compared to the permanent paraffin sections. Among the 85 patients, 75 had malignancies in frozen sections, while 10 patients showed otherwise. In the 85 malignant cases, age, sex, the volume of effusion, thoracoscopic findings, as well as the final pathological diagnosis (lung non-lung origin) were included in univariate analysis for an association with non-malignant frozen section results. High adhesion grade and malignancy other than lung cancer were significant factors associated with frozen section negative cases in a multivariable analysis.

Conclusions: Taking fresh frozen sections during MT using a flex-rigid bronchoscope is a useful diagnostic modality with reliable sensitivity for malignancy. However, if the pre-procedural diagnosis is likely to be a malignancy other than lung cancer, and if severe adhesions are present in the pleural cavity, the final pathological confirmation should be determined based on permanent paraffin sections, not only on fresh frozen sections.
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http://dx.doi.org/10.21037/jtd-20-1809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797841PMC
December 2020

Nicotine Dependence and Stress Susceptibility in E-Cigarette Smokers: The Korea National Health and Nutrition Examination Survey 2013-2017.

Tuberc Respir Dis (Seoul) 2021 Apr 6;84(2):159-166. Epub 2021 Jan 6.

Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.

Background: E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of non-smokers or combustible cigarette smokers in Korea.

Methods: In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013-2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use).

Results: Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than non-smokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p<0.001) and who planned to quit smoking within 6 months (39.1% vs. 35.7%, p<0.05) was greater than that of smokers. E-smokers perceived stress as "very much" (7.0% vs. 4.4%, p<0.001) and "a lot" (29.1% vs. 20.5%, p<0.001) compared to non-smokers. Suicidal ideation (6.5% vs. 4.7%, p<0.001), plans (2.4% vs. 1.3%, p<0.001), and attempts (1.1% vs. 0.5%, p<0.001) were higher in e-smokers than in non-smokers. Depressive episodes in 1 year (14.2% vs. 11.4%, p<0.05) and suicidal plans (2.4% vs. 1.8%, p<0.05) were more frequent among e-smokers than among smokers.

Conclusion: E-smokers were younger, more educated, and had a higher income, but they were more dependent on nicotine and susceptible to stress than non-smokers and smokers. Smoking cessation counseling should be tailored according to the characteristics of e-smokers.
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http://dx.doi.org/10.4046/trd.2020.0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010419PMC
April 2021

Impact of Combined Chronic Obstructive Pulmonary Disease Status and Systemic Inflammation on Outcome of Advanced NSCLC: Multicenter Retrospective Cohort Study.

Int J Chron Obstruct Pulmon Dis 2020 14;15:3323-3334. Epub 2020 Dec 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: In patients with non-small cell lung cancer (NSCLC), both chronic obstructive pulmonary disease (COPD) and systemic inflammatory biomarkers, such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), have significant association with prognosis. NLR and PLR also predict mortality in patients with COPD alone. A combination of the two parameters may be helpful in a more individualized approach for predicting prognosis in NSCLC.

Methods: Medical records of patients with stage IIIB and IV NSCLC from January 2012 to January 2018 in seven university hospitals were reviewed. Patients were categorized into four subgroups based on pulmonary function test results and cutoffs for NLR or PLR.

Results: A total of 277 patients were evaluated and categorized into non-COPD and COPD groups; 194 patients were in the non-COPD group and 83 patients were in the COPD group. The non-COPD group showed significantly longer overall survival (OS) compared with the COPD group (P = 0.019). Median survival was significantly different between high/low PLR groups (P < 0.001), between high/low NLR groups (P = 0.001), and between high/low c-reactive protein (CRP) groups (P < 0.001). PLR, NLR and CRP showed significant correlations with each other. PLR showed a significant negative linear correlation with FVC (absolute) (r = -0.149, P = 0.015), FVC (%) (r = -0.192, P = 0.002), DLCO (absolute) (r = -0.271, P < 0.001), DLCO (%) (r = -0.139, P = 0.032), and NLR (r = 0.718, P < 0.001). In the multivariate analysis, the high PLR, COPD sub-group showed significantly higher risk for mortality (HR 2.066 (1.175-3.633), P = 0.012) compared with the low-PLR non-COPD group. However, COPD-NLR subtype was not an independent predictor for OS.

Conclusion: A combination of COPD status and PLR may be a cost-effective and readily available prognostic marker in patients with advanced NSCLC.
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http://dx.doi.org/10.2147/COPD.S274354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753914PMC
June 2021

Direct Switch from Tiotropium to Indacaterol/Glycopyrronium in Chronic Obstructive Pulmonary Disease Patients in Korea.

Tuberc Respir Dis (Seoul) 2021 Apr 22;84(2):96-104. Epub 2020 Dec 22.

Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once-daily in COPD patients in Korea.

Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once-daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted postbronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV1 at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment.

Results: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV1 versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, -0.81), and rescue medication use (Δ, -0.09 puffs/day). Both treatments were well tolerated by patients.

Conclusion: A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.
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http://dx.doi.org/10.4046/trd.2020.0109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010420PMC
April 2021

The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway.

Tuberc Respir Dis (Seoul) 2020 Dec 8;83(Supple 1):S63-S74. Epub 2020 Oct 8.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury.

Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks.

Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased.

Conclusion: CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.
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http://dx.doi.org/10.4046/trd.2020.0112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837382PMC
December 2020

Regional emphysema score is associated with tumor location and poor prognosis in completely resected NSCLC patients.

BMC Pulm Med 2020 Sep 11;20(1):242. Epub 2020 Sep 11.

Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul, 03312, Republic of Korea.

Background: Lung cancer is a frequent comorbidity of chronic obstructive pulmonary disease (COPD). However, the local risk of developing lung cancer related to regional emphysema distribution and clinical outcome has not been investigated. Our aim was to evaluate the impact of regional emphysema score (RES) on tumor location and prognosis in non-small cell lung cancer (NSCLC) patients.

Methods: We enrolled 457 patients who underwent curative surgery for NSCLC at seven hospitals at The Catholic University of Korea from 2014 to 2018. Emphysema was visually assessed for each lobe, with the lingula as a separate lobe. Semi-quantitative emphysema scoring was classified as follows: 0 = none, 0.5 = 1 to 10%, 1 = 11 to 25%, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. An RES was given to each of the six lung zone: the upper, middle, and lower lobes in the right and left lungs.

Results: There were 145 patients in the high RES (≥ 3) group and 312 in the low RES (< 3) group. The mean RES in each lobe with cancer was significantly higher than that in other lobes without cancer (0.51 vs. 0.37, P <  0.001). This group showed significantly shorter disease-free survival (P <  0.001), in addition, presence of COPD, low diffusing capacity of the lung for carbon monoxide (< 80), smoking status, and poor differentiation were more frequent in this group. Also, cancer in a lobe with a higher RES (odds ratio (OR) = 1.56; 95% confidence interval (CI:1.01-2.42; P = 0.04), pathologic stage ≥ III (OR = 2.23; 95% CI: 1.28-3.89; P <  0.001), and poor differentiation (OR = 1.99; 95% CI: 1.22-3.21; P <  0.001) were independent factors for tumor recurrence.

Conclusions: The regional severity of emphysema by visual qualification was associated with the location of lung cancer, and was an independently poor prognostic factor for tumor recurrence in completely resected NSCLC patients.
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http://dx.doi.org/10.1186/s12890-020-01268-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488536PMC
September 2020

Impact of smoking amount on clinicopathological features and survival in non-small cell lung cancer.

BMC Cancer 2020 Sep 3;20(1):848. Epub 2020 Sep 3.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Screening for early detection of lung cancer has been performed in high-risk individuals with smoking history. However, researches on the distribution, clinical characteristics, and prognosis of these high-risk individuals in an actual cohort are lacking. Thus, the objective of this study was to retrospectively review characteristics and prognosis of patients with smoking history in an actual lung cancer cohort.

Methods: The present study used the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017. Patients with non-small cell lung cancer were enrolled. They were categorized into high and low-risk groups based on their smoking history using the national lung screening trial guideline. Distribution, clinical characteristics, and survival data of each group were estimated.

Results: Of 439 patients, 223 (50.8%) patients were in the high-risk group. Patients in the high-risk group had unfavorable clinical characteristics and tumor biologic features. Overall survival of the high-risk group was significantly shorter than that of the low-risk group with both early (I, II) and advanced stages (III, IV). In multivariate analysis, heavy smoking remained one of the most important poor clinical prognostic factors in patients with lung cancer. It showed a dose-dependent relationship with patients' survival.

Conclusions: High-risk individuals had poor clinical outcomes. Patients' prognosis seemed to be deteriorated as smoking amount increased. Therefore, active screening and clinical attention are needed for high-risk individuals.
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http://dx.doi.org/10.1186/s12885-020-07358-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469911PMC
September 2020

Containment of a healthcare-associated COVID-19 outbreak in a university hospital in Seoul, Korea: A single-center experience.

PLoS One 2020 14;15(8):e0237692. Epub 2020 Aug 14.

Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Our hospital experienced the first healthcare-associated COVID-19 outbreak in Seoul at the time the first COVID-19 cases were confirmed in Korea. The first confirmed COVID-19 patient was a hospital personnel who was in charge of transferring patients inside our hospital. To contain the virus spread, we shutdown our hospital, and tested all inpatients, medical staff members, and employees.

Methods: We retrospectively analyzed the results of SARS-CoV-2 RT-PCR testing according to the contact history, occupation, and presence of respiratory symptoms. Closed-circuit television (CCTV) was reviewed in the presence of an epidemiologist to identify individuals who came into contact with confirmed COVID-19 patients.

Results: A total of 3,091 respiratory samples from 2,924 individuals were obtained. Among 2,924 individuals, two inpatients, and one caregiver tested positive (positivity rate, 0.1%). Although all confirmed cases were linked to a general ward designated for pulmonology patients, no medical staff members, medical support personnel, or employees working at the same ward were infected. Contact with confirmed COVID-19 cases was frequent among inpatients and medical support personnel. The most common contact area was the general ward for pulmonology patients and medical support areas, including clinical and imaging examination rooms. Finally, the total number of hospital-associated infections was 14, consisting of four diagnosed at our hospital and ten diagnosed outside the hospital.

Conclusions: The robust control of the COVID-19 outbreak further minimized the transmission of SARS-CoV-2 in the hospital and local communities. However, there was also a debate over the appropriate period of hospital shutdown and testing of all hospital staff and patients. Future studies are required to refine and establish the in-hospital quarantine and de-isolation guidelines based on the epidemiological and clinical settings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237692PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428087PMC
August 2020

Effects of chronic intermittent hypoxia caused by obstructive sleep apnea on lipopolysaccharide-induced acute lung injury.

Exp Lung Res 2020 11 13;46(9):341-351. Epub 2020 Aug 13.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Aim Of The Study: Obstructive sleep apnea (OSA) is a common disease associated with significant morbidity and mortality. Sleep quality is an important issue; some patients with acute lung injury (ALI) have underlying OSA. However, the potential influences of OSA on ALI have not been reported until now. In this study, we evaluated the impact of preceding intermittent hypoxia (IH), a typical characteristic of OSA, on lipopolysaccharide (LPS)-induced ALI in a mouse model.

Methods: C57BL/6J mice were randomly divided into four groups: room air-control (RA-CTL), intermittent hypoxia-control (IH-CTL), room air-lipopolysaccharide (RA-LPS), and intermittent hypoxia-lipopolysaccharide (IH-LPS) groups. The mice were exposed to RA or IH (20 cycles/h, FiO nadir 7 ± 0.5%, 8 h/day) for 30 days. The LPS groups received intratracheal LPS on day 28.

Results: The IH-LPS group tended to exhibit more severe inflammation, fibrosis, and oxidative stress compared to the other groups, including the RA-LPS group. Total cell, neutrophil, and eosinophil counts in bronchoalveolar lavage fluid increased significantly in the IH-LPS group compared to the RA-LPS group. Compared to the RA-LPS group, the hydroxyproline level increased significantly in the IH-LPS group. In addition, the IH-LPS group exhibited significantly more terminal deoxynucleotidyl transferase dUTP nick end labeled-positive cells compared to the RA-LPS group.

Conclusions: We found that prior IH may negatively impact LPS-induced ALI in a mouse model. This result suggests that ALI in patients with OSA may be more of a concern. Further research into the mechanisms underlying the effects of IH on ALI is needed.
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http://dx.doi.org/10.1080/01902148.2020.1804646DOI Listing
November 2020

Association between triglyceride glucose index and obstructive sleep apnea risk in Korean adults: a cross-sectional cohort study.

Lipids Health Dis 2020 Aug 8;19(1):182. Epub 2020 Aug 8.

Division of Pulmonary, Critical Care and Sleep Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Triglyceride glucose (TyG) index is a reliable marker of insulin resistance, which is linked to obstructive sleep apnea (OSA). However, the relationship between TyG index and OSA has not been adequately assessed. This study aimed to evaluate the association between TyG index and OSA.

Methods: TyG index was assessed in 180 (mean age: 48.6 ± 13.8 years; 73.9% male) consecutive Korean adults with suspected OSA admitted to the sleep clinic at St. Paul's Hospital between 2010 and 2012. The occurrence of more than 5 apnea-hypopnea index (AHI) events/h was used to define OSA. TyG index was calculated using the following equation: In [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. All participants were grouped according to TyG index tertiles. Multivariate logistic regression analysis was used to determine factors associated with increased OSA risk.

Results: The overall prevalence of OSA in study participants was determined to be 83.9%. The prevalence of OSA increased (I [lowest]: 71.6%; II: 88.7%; III [highest]: 91.4%), and lowest peripheral oxygen saturation (SpO) levels decreased (I: 83.3 ± 8.5%; II: 79.9 ± 8.7%; III: 79.0 ± 8.3%), as TyG index tertile increased (P < 0.05). TyG index was correlated with AHI (r = 0.179) and lowest SpO (r = - 0.188) (P < 0.05, respectively). Univariate linear regression analysis revealed an association between TyG and AHI (β = 10.084; P = 0.016). Multivariate logistic regression analysis showed that TyG index (odds ratio [OR]: 3.348; 95% confidence interval [CI]: 1.081-10.372), age ≥ 55 years (OR: 5.426; 95% CI: 1.642-17.935), and obesity (OR: 3.801; 95% CI: 1.468-9.842) were associated with increased OSA risk (all P < 0.05). The optimal TyG index cut-off value for predicting OSA was 8.83 (sensitivity: 61.6%; specificity: 69.0%; area under the curve: 0.688; P = 0.001). The predictive value of the OSA cut-off value improved when age ≥ 55 years and obesity were considered.

Conclusion: Increased TyG index was independently associated with increased OSA risk.
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http://dx.doi.org/10.1186/s12944-020-01358-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414547PMC
August 2020

The Influence of Gastroesophageal Reflux Disease on Daytime Sleepiness and Depressive Symptom in Patients With Obstructive Sleep Apnea.

J Neurogastroenterol Motil 2021 Apr;27(2):215-222

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: As there is insufficient evidence for a relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA), we investigated whether OSA diagnosed by polysomnography (PSG) is related to GERD.

Methods: A total of 402 subjects was evaluated. Overnight PSG was performed and a few questionnaires on GERD, anxiety, depression, and daytime sleepiness were administered. An apnea-hypopnea index < 5 was the classification criterion for subjects without OSA. Subjects with heartburn or acid regurgitation at least once a week were classified as having GERD.

Results: Among the 402 subjects, 318 had OSA and 84 did not. The prevalence of GERD was 12.9% among patients with OSA and 10.7% among those without ( = 0.590). The prevalence of GERD did not correlate with OSA severity ( = 0.474). Patients with OSA with GERD had higher Stanford Sleepiness Scale ( = 0.004), Epworth Sleepiness Scale ( = 0.001), and depression ( < 0.001) scores than patients with OSA without GERD. Subjects with nocturnal gastroesophageal reflux symptoms had a higher body mass index, waist-to-height ratio, and waist circumference-to-height index than those without symptoms. Multiple logistic regression showed that higher Epworth Sleepiness Scale and depression scores were independent factors associated with GERD in patients with OSA.

Conclusions: The prevalence of GERD in patients with OSA was 12.9%. The prevalence of GERD did not correlate with OSA severity. Daytime sleepiness and depression seem to be associated with GERD in patients with OSA, while nocturnal reflux symptoms seem to be related to obesity in OSA.
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http://dx.doi.org/10.5056/jnm20071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026368PMC
April 2021

Blood lead levels in relation to smoking and chronic obstructive pulmonary disease (COPD): a study from Korean National Health and Nutrition Examination Survey (KNHANES).

J Thorac Dis 2020 Jun;12(6):3135-3147

Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea.

Background: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD.

Methods: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels.

Results: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05).

Conclusions: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.
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http://dx.doi.org/10.21037/jtd-20-739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330752PMC
June 2020

Clinical significance of anemia as a prognostic factor in non-small cell lung cancer carcinoma with activating epidermal growth factor receptor mutations.

J Thorac Dis 2020 May;12(5):1895-1902

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Anemia is a frequent finding in cancer patients. Pre-treatment anemia is known to be associated with poor survival after surgery or stereotactic body radiation therapy of non-small cell lung cancer (NSCLC). However, little study was conducted in NSCLC with activating epidermal growth factor receptor (EGFR) mutations.

Methods: This was a multicenter retrospective study conducted in seven university teaching hospitals in the Republic of Korea from January 2009 to February 2016. A total of 290 patients were diagnosed with NSCLC harboring sensitizing EGFR mutations and treated with EGFR-tyrosine kinase inhibitor (TKI) as 1st line. Of these patients, 104 met the exclusion criteria. Pre-treatment anemia was defined according to World Health Organization criteria (Hb concentration <13 g/dL for men and <12 g/dL for women).

Results: A total of 186 patients were finally included for analysis. Of these patients, 86 (46.2%) and 100 (53.8%) patients were classified into anemia and non-anemia groups, respectively. The anemia group had shorter median overall survival (OS) than the non-anemia group [24.83 (95% CI, 17.49-32.17) months 42.10 (95% CI, 31.87-52.34) months, P=0.031]. In multivariate analysis, anemia (aHR, 2.573; 95% CI, 1.122-5.901; P=0.026) was only independent factors for poor OS.

Conclusions: Our study suggests that pre-treatment anemia is a significant poor prognostic factor for OS of NSCLC patients with EGFR mutations treated with EGFR-TKI.
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http://dx.doi.org/10.21037/jtd-19-3932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330305PMC
May 2020

Pleural Neutrophil-to-Lymphocyte Ratio May Be Associated With Early Disease Progression in Stage IV Non-small Cell Lung Cancer.

In Vivo 2020 Jul-Aug;34(4):2179-2185

Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background/aim: While blood neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in NSCLC, however few studies have focused on pleural fluid white blood cell differential count. We conducted a retrospective multicenter cohort study to evaluate the predictive value of pleural NLR in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE).

Patients And Methods: From the multicenter lung cancer cohort, 134 epidermal growth factor receptor (EGFR) wild-type patients with NSCLC were selected for evaluation. Receiver operating characteristic (ROC) curve analysis was performed for pretreatment pleural NLR to determine the cut-off value for predicting disease progression within 100 days after the diagnosis.

Results: The low-pleural NLR group showed significantly longer overall survival (OS) and progression free survival (PFS) compared to the high-pleural NLR group. After stratification using quartile cut-off values of pleural NLR, the correlation between risk of disease progression and pleural NLR was shown to be dose-dependent. The multivariate analysis on PFS showed that high-pleural NLR (p=0.004) was an independent predictor for shorter PFS with HR of 1.036 (1.011-1.061).

Conclusion: Increased pleural NLR is predictive of early disease progression in EGFR mutation wild-type NSCLC patients with MPE.
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http://dx.doi.org/10.21873/invivo.12027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439889PMC
June 2021

Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study.

BMC Infect Dis 2020 Jun 23;20(1):446. Epub 2020 Jun 23.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 56, Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea.

Background: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.

Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15-34 years), middle (35-59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed.

Results: Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.

Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.
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http://dx.doi.org/10.1186/s12879-020-05157-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310538PMC
June 2020

Decline in Carbon Monoxide Transfer Coefficient in Chronic Obstructive Pulmonary Disease.

J Clin Med 2020 May 18;9(5). Epub 2020 May 18.

Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Background: Although a reduced carbon monoxide transfer coefficient (Kco) is an important feature in chronic obstructive pulmonary disease (COPD), how it changes over time and its relationship with other clinical outcomes remain unclear. This study evaluated longitudinal changes in Kco and their relationship with other clinical outcomes.

Methods: We evaluated patients with COPD from the Korean Obstructive Lung Disease cohort, followed up for up to ten years. Random coefficient models were used to assess the annual change in Kco over time. Participants were categorized into tertiles according to Kco decline rate. Baseline characteristics and outcomes, including changes in FEV1 and emphysema index, incidence of exacerbations, and mortality, were compared between categories.

Results: A decline in Kco was observed in 92.9% of the 211 enrolled participants with COPD. Those with the most rapid decline (tertile 1) had a lower FEV1/FVC% (tertile 1: 43.8% ± 9.7%, tertile 2: 46.4% ± 10.5%, tertile 3: 49.2% ± 10.4%, = 0.008) and a higher emphysema index at baseline (27.7 ± 14.8, 22.4 ± 16.1, 18.1 ± 14.5, respectively, = 0.001). Tertile 3 showed a lower decline rate in FEV1 (16.3 vs. 27.1 mL/yr, = 0.017) and a lower incidence of exacerbations (incidence rate ratio = 0.66, 95% CI = 0.44-0.99) than tertile 1. There were no differences in the change in emphysema index and mortality between categories.

Conclusion: Most patients with COPD experienced Kco decline over time, which was greater in patients with more severe airflow limitation and emphysema. Decline in Kco was associated with an accelerated decline in FEV1 and more frequent exacerbations; hence, this should be considered as an important outcome measure in further studies.
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http://dx.doi.org/10.3390/jcm9051512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290811PMC
May 2020

Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study.

Int J Chron Obstruct Pulmon Dis 2020 17;15:809-819. Epub 2020 Apr 17.

GSK, Shanghai, People's Republic of China.

Purpose: Previous studies demonstrating efficacy and safety of once-daily umeclidinium (UMEC) in patients with chronic obstructive pulmonary disease (COPD) have included few Asian patients. This study evaluated efficacy and safety of UMEC 62.5 mcg versus placebo in Asian patients with COPD.

Patients And Methods: A Phase III, randomized, double-blind, parallel-group study. Patients (aged ≥40 years with COPD, pre-, and post-albuterol forced expiratory volume in 1 s [FEV]/forced vital capacity ratio <0.70 and low risk of exacerbations) were randomized 2:1 to once-daily UMEC 62.5 mcg or placebo via the ELLIPTA inhaler for 24 weeks. Primary endpoint was change from baseline (CFB) in trough FEV on Day 169. Secondary endpoints were weighted mean FEV over 0-6 hrs post-dose on Day 1 and CFB in Transition Dyspnea Index (TDI) focal score on Day 168.

Results: A total of 306 patients were included in the modified intent-to-treat population (UMEC: 205; placebo: 101). UMEC versus placebo provided a statistically significant improvement in least squares (LS) mean trough FEV between baseline and Day 169 (154 mL [95% confidence interval (CI): 113, 194]; p<0.001). A clinically meaningful difference of 125 mL in favor of UMEC (95% CI: 103, 147; p<0.001) was also seen in LS weighted mean FEV 0-6 hrs post-dose on Day 1. A LS mean treatment difference in TDI focal score of 0.9 units in favor of UMEC was seen on Day 168 (95% CI: 0.3, 1.5; p=0.004). Incidence of on-treatment adverse events (AEs) was lower in the placebo (55%) versus UMEC arm (60%); non-fatal serious AEs, drug-related AEs, and AEs leading to withdrawal were similar with UMEC and placebo.

Conclusion: Once-daily UMEC 62.5 mcg resulted in statistically significant and clinically meaningful improvements in lung function and dyspnea, compared with placebo, in Asian patients with COPD, with no new safety concerns observed.
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http://dx.doi.org/10.2147/COPD.S215011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173840PMC
June 2021

Smoking is associated with pneumonia development in lung cancer patients.

BMC Pulm Med 2020 May 1;20(1):117. Epub 2020 May 1.

Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 327, Sosa-ro, Bucheon-si, Gyeonggi-do, 14647, Republic of Korea.

Background: Various host factors can promote pneumonia susceptibility of lung cancer patients. However, data about risk factors for pneumonia in lung cancer patients receiving active treatments such as chemotherapy, radiotherapy, and surgical intervention are limited. Thus, the purpose of this study was to identify risk factors for pneumonia development in lung cancer patients.

Methods: The present study used a lung cancer cohort of the Catholic Medical Center at the Catholic University of Korea from January 2015 to December 2018. Pneumonia was defined by the presence of a new or progressive infiltration on chest imaging together with any of the following: new onset purulent sputum, change in character of chronic sputum, and fever. We ruled out noninfectious infiltration such as drug or radiation toxicity and hydrostatic pulmonary edema. We especially excluded those if computed tomography revealed sharp demarcation consolidation or ground glass opacity limited radiation field.

Results: A total of 413 patients were enrolled in this study. Pneumonia occurred in 118 (28.6%) patients. The pneumonia group had significantly worse overall survival (OS) than the non-pneumonia group (456.7 ± 35.0 days vs. 813.4 ± 36.1 days, log rank p < 0.001). In patients with pneumonia, OS was shorter in ex-smokers and current smokers than in never smokers (592.0 ± 101.0 days vs. 737.0 ± 102.8 days vs. 1357.0 days, log rank p < 0.001). Age (hazard ratio [HR]: 1.046; 95% confidence interval [CI]: 1.019-1.074; p = 0.001), clinical stage IV (HR: 1.759; 95% CI: 1.004-3.083; p = 0.048), neutropenia (HR: 2.620; 95% CI: 1.562-4.396; p < 0.001], and smoking (HR: 2.040; 95% CI: 1.100-3.784; p = 0.024) were independent risk factors of pneumonia development in lung cancer patients in multivariate analysis. In subgroup analysis for patients treated with chemotherapy, age (HR: 1.043; 95% CI: 1.012-1.074; p = 0.006), neutropenia (HR: 3.199; 95% CI: 1.826-5.605; p < 0.001), and smoking (HR: 2.125; 95% CI: 1.071-4.216; p = 0.031) were independent risk factors of pneumonia development.

Conclusions: Smoking and neutropenia were risk factors affecting pneumonia development in the total group and subgroup of patients with lung cancer.
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http://dx.doi.org/10.1186/s12890-020-1160-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195765PMC
May 2020

Validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale.

Korean J Intern Med 2021 01 24;36(1):135-144. Epub 2020 Feb 24.

Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: This study evaluated the validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale (WSWS-K) for use in clinical practice and research on Korean smokers.

Methods: The Wisconsin Smoking Withdrawal Scale was translated into Korean and then back-translated into English. The authors reviewed the translation and back-translation and approved the final questionnaire draft. The validity and reliability of the WSWS-K were evaluated based on data collected from 300 participants. Construct validity was evaluated with a confirmatory factor analysis. Criterion-related validity was assessed by examining the relationships between the subscales of the WSWS-K and the matched items of the Korean version of the Minnesota Nicotine Withdrawal Scale (MNWS-K).

Results: The participants were predominantly male (93.6%) and the mean age was 59.23 ± 15.19 years. The confirmatory factor analysis revealed that fit indices (namely, the goodness-of-fit index, adjusted goodness-of-fit index, comparative fit index, and the normed fit index) exceeded or approached 0.9. Cronbach's alpha for the entire scale was 0.87. The total score of the WSWS-K had a statistically significant positive correlation with that of the MNWS-K (Pearson's correlation coefficient, 0.768; p < 0.01). Additionally, we performed linear regression between the WSWS-K and MNWS-K scores after adjusting for age, gender, comorbidity, and smoking history. After this adjustment, the p value of the WSWS- K was < 0.001.

Conclusion: The WSWS-K had satisfactory validity and reliability. The WSWS- K can be used with acceptable validity and reliability in research and clinical evaluation of Korean smokers.
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http://dx.doi.org/10.3904/kjim.2018.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820660PMC
January 2021

Effects of long term normobaric hyperoxia exposure on lipopolysaccharide-induced lung injury.

Exp Lung Res 2020 Feb - Mar;46(1-2):44-52. Epub 2020 Feb 18.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Prolonged exposure to hyperoxia can cause injury to normal lung tissue. However, patients with acute hypoxic respiratory failure are frequently exposed to very high oxygen levels. This study investigated the effects of long term normobaric hyperoxia exposure in a mouse model of acute severe lung injury (SLI). C57BL/6J mice were injected intratracheally with lipopolysaccharide (LPS, 4 mg/kg) to induce acute lung injury. After 2 h, mice were divided into two groups, and then exposed to room air or hyperoxic conditions for 48 h. Animals in the hyperoxia group were placed within their cages in a Plexiglass chamber with an atmosphere of 95% O maintained constant using an oxygen analyzer. After exposure to normoxia (N) or hyperoxia (H) for 48 h, the left lungs were collected for tissue paraffin block or oxidative stress assay. One lobe of the right lung was collected for lung/body weight ratio. The lung injury score and the mean linear intercept were evaluated in hematoxylin and eosin -stained lungs. The biochemical tests were performed by using ELISA assay. Lung injury scoring, lung/body weight, and mean linear intercept were not significantly different between the N + LPS (NLPS) and H + LPS (HLPS) groups. Similar trends were observed in hydroxyproline and transforming growth factor-β (TGF-β) levels. Total cell and neutrophil counts in bronchoalveolar lavage fluid showed no significant differences between NLPS and HLPS groups. Histological analyses demonstrated more severe lung injury and fibrosis in the NLPS group than in the HLPS group. In addition, interleukin (IL)-1β was significantly decreased in the HLPS group compared to the NLPS group. Other inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-6, showed similar trends. The malondialdehyde (MDA) level was significantly lower in the HLPS group than in the NLPS group. Exposure to hyperoxia did not augment lung injury in the LPS-induced lung injury model, and some indicators even showed better outcomes. These results suggest that long-term high-oxygen therapy in patients with SLI has low risk of lung injury.
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http://dx.doi.org/10.1080/01902148.2020.1725183DOI Listing
August 2021

The health-related quality-of-life of chronic obstructive pulmonary disease patients and disease-related indirect burdens.

Korean J Intern Med 2020 09 20;35(5):1136-1144. Epub 2020 Feb 20.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea.

Background/aims: Many chronic obstructive pulmonary disease (COPD) patients have physical limitations. We investigated EuroQol five-dimensions five-level (EQ-5D-5L) of COPD patients to assess quality of life, and assessed indirect burden including time expenditure to visit doctor, home care rate, and caregiver related burden.

Methods: We recruited 355 COPD patients according to severity of airflow limitation that severity was set at 10% mild, 40% moderate, 30% severe, and 20% very severe in two primary and 11 secondary/tertiary hospitals. Eligible patients were aged ≥ 40 years, who have been diagnosed with COPD for more than 1 year. Patients were recruited between June 2015 and October 2016.

Results: The quality of life tended to decline with age, from mild to very severe impairment, as revealed by the EQ-5D-5L scores and the EQ visual analog scale. Family caregivers accompanied 22.6% of patients who visited outpatient clinics, and 25% of stage IV COPD patients. During emergency visits and hospitalization, this figure increased to > 60%. The home care rates were 28.5% for stage I patients, and 34.4, 31.8, and 52% for stage II to IV patients, respectively. The percentage of caregivers who stopped working was 13.6%. The EQ-5D index was strongly associated with the dyspnea scale (r = -0.64, p < 0.001). The average required time to see a doctor and visit the pharmacy was 154 minutes.

Conclusion: In patients with COPD, the EQ-5D index decreased and disease-related home caregiving increased with airflow limitation. We considered the caregiver- related burden when making a strategy for COPD management.
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http://dx.doi.org/10.3904/kjim.2018.398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487298PMC
September 2020

Intermittent hypoxia exacerbates tumor progression in a mouse model of lung cancer.

Sci Rep 2020 02 5;10(1):1854. Epub 2020 Feb 5.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P < 0.01) and volume (P < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after IH exposure. CIH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth.
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http://dx.doi.org/10.1038/s41598-020-58906-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002457PMC
February 2020
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