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Tai Joon An,1 Yeun Jie Yoo,2 Jeong Uk Lim,1 Wan Seo,3 Chan Kwon Park,1 Chin Kook Rhee,4 Hyoung Kyu Yoon1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Rehabilitation Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea; 3Department of Internal Medicine, St. Peter’s Hospital, Seoul, Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, KoreaCorrespondence: Hyoung Kyu Yoon Tel +82 2-3779-2213Email cmcyhg@gmail.comBackground: Evaluating the diaphragm muscle in chronic obstructive pulmonary disease (COPD) is important. However, the role of diaphragm ultrasound (DUS) in distinguishing the exacerbation status of COPD (AECOPD) is not fully understood. We set this study to evaluate the role of DUS as a biomarker for distinguishing the AECOPD.Methods: COPD patients who underwent DUS were enrolled between March 2020 and November 2020. The diaphragm thickening fraction (TFmax) and diaphragm excursion (DEmax) during maximal deep breathing were measured. Patients were divided into exacerbation and stable groups. Demographics, lung function, and DUS findings were compared between the two groups. Receiver operating characteristic curve and univariate/multivariate logistic regression analyses were performed.Results: Fifty-five patients were enrolled. The exacerbation group had a lower body mass index (BMI) (20.9 vs 24.2, p = 0.003), lower TFmax (94.8 ± 8.2% vs 158.4 ± 83.5%, p = 0.010), and lower DEmax (30.8 ± 11.1 mm vs 40.5 ± 12.5 mm, p = 0.007) compared to stable group. The areas under the TFmax (0.745) and DEmax (0.721) curves indicated fair results for distinguishing AECOPD. The patients were divided into low and high TFmax and DEmax groups based on calculated cut-off values. Low TFmax (odds ratio [OR] 8.40; 95% confidence interval [CI] 1.55– 45.56) and low DEmax (OR 11.51; 95% CI 1.15– 115.56) were associated with AECOPD after adjusting for age, sex, BMI, and lung functions.Conclusion: DUS showed the possibility of an imaging biomarker distinguishing AECOPD from stable status.Keywords: COPD, exacerbation, diaphragm, ultrasound, biomarker

Jeong Uk Lim,1 Hye Seon Kang,2 Chang Dong Yeo,3 Ju Sang Kim,4 Chan Kwon Park,1 Yong Hyun Kim,2 Jin Woo Kim,5 Seung Joon Kim,6,7 Sang Haak Lee3,7 1Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea; 3Division 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; 4Division of Pulmonary, Critical Care and Sleep Allergy, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 6Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 7Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Yong Hyun KimDivision of Pulmonary, Allergy and Critical Care Medicine, 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 KoreaTel +82-32-340-7039Fax +82-32-340-2669Email kyh30med@catholic.ac.krBackground: 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.Keywords: chronic obstructive pulmonary disease, non-small cell lung cancer, survival, platelet, lymphocyte, inflammation, biomarker

Objectives Depression is a major comorbidity that affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). COPD patients with depression are hospitalized more frequently, and show more acute exacerbations, decreased physical and social activities, and higher mortality compared to their non-depressed counterparts. In the present study, we investigated the clinical impact of depressive symptoms and associated clinical factors in Korean patients with COPD by evaluating multicenter cohort data. Materials and methods Patients with COPD enrolled in the Korean COPD Subtype Study, a multicenter observational study, from December 2011 to October 2014 were selected for evaluation. The initial evaluation of all patients included pulmonary function tests, 6 min walk distance (6MWD), the COPD Assessment Test (CAT), and the COPD-specific version of the St. George's Respiratory Questionnaire (SGRQ-C). Significant depression was defined as a Beck Depression Inventory-II (BDI-II) score ≥17. Results Among the 270 study patients, 19.6% had significant depression. The depressed group showed a higher proportion of females (41.4%), lower body mass index (BMI), and lower education level compared to the non-depressed group (p = 0.002, p = 0.008, and p = 0.019, respectively). The depressed group had significantly higher CAT and SGRQ-C scores, as well as a lower 6MWD, compared to the non-depressed group based on 6 month-interval serial measurements over 3 years. The total SGRQ-C score and the symptoms, activity, and impact domain scores were significant predictors of depression (area under curves [AUCs] of 0.699 [0.613-0.786], 0.670 [0.581-0.758], 0.680 [0.589-0.770], and 0.689 [0.603-0.776], respectively). From CAT score domains, sleep and energy scores were significant predictors of depression (AUCs of 0.619 [0.522-0.715] and 0.595 [0.504-0.685], respectively). SGRQ-C score, low BMI, and decreased 6MWD were significantly associated with depression in a multivariable analysis. Conclusion A considerable proportion of patients with COPD had depression, and a high SGRQ-C score, low BMI, and low 6MWD were significantly associated with depression. As improving quality of life in this subgroup is difficult, physicians should be more active in screening patients with significant depression.

Jeong Uk Lim, Chang Dong Yeo, Chin Kook Rhee, Hye Seon Kang, Chan Kwon Park, Ju Sang Kim, Jin Woo Kim, Seung Joon Kim, Hyoung Kyu Yoon, Sang Haak LeeDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaObjectives: A significant proportion of non-small cell lung cancer (NSCLC) patients are never-smokers. However, the clinical impact of spirometrically diagnosed chronic obstructive pulmonary disease (COPD) on the prognosis of never-smoking NSCLC has not been evaluated in the context of treatment modalities and other cancer-related factors. In the present study, we evaluated the clinical impact of COPD in non-smoking NSCLC patients, and correlations between COPD and other previously unevaluated clinical variables.Materials and methods: Lung cancer patients (stages I to IV) diagnosed with NSCLC between January 2008 and December 2015 at six university hospitals were enrolled in the study cohort and retrospectively evaluated. Clinical parameters were compared between spirometrically diagnosed COPD and non-COPD groups. Correlations between COPD status and other variables were evaluated. In order to reduce the effect of potential confounders and selection bias, we performed adjustment for differences in baseline parameters by using propensity score matching (PSM). After PSM, clinical variables were evaluated for their effects on overall survival (OS).Results: Of the 345 patients enrolled in the study, 277 were categorized as non-COPD and 68 as COPD. Old age, male gender, and wild-type EGFR were significantly correlated with COPD. By univariate analysis of 218 patients in a propensity score matched cohort, not receiving active anticancer treatment, advanced stage, and COPD were significantly associated with shorter OS. Multivariate analysis showed that not receiving active anticancer treatment, advanced cancer stage, and COPD (P=0.044, HR: 1.526, 95% CI: 1.012–2.300) were significant predictors of shorter OS.Conclusion: In the present study, never-smoker NSCLC patients with COPD had shorter OS times, compared to non-COPD never-smoker NSCLC patients.Keywords: never smoker, overall survival, risk factor &nbsp

Jeong Uk Lim, Chang Dong Yeo, Chin Kook Rhee, Yong Hyun Kim, Chan Kwon Park, Ju Sang Kim, Jin Woo Kim, Seung Joon Kim, Hyoung Kyu Yoon, Sang Haak Lee Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Objectives: Focusing on the advanced non-small cell lung cancer (NSCLC) patients without driver mutations can elucidate the clinical impact of COPD on treatment outcomes. The present study evaluated the effects of COPD on the overall survival of driver mutation-negative NSCLC patients undergoing conventional chemotherapy as the first-line treatment. Patients and methods: Medical records of stage IIIB and IV NSCLC patients from January 2008 to December 2015 from six university hospitals were reviewed. Results: The total study population consisted of 197 patients; 92 (46.7%) were COPD patients and 105 (53.3%) were non-COPD patients. The median survival in the non-COPD group was 11.5 months, compared to 9.2 months in the COPD group. Univariate analysis showed that old age (>70 years), high Eastern Cooperative Oncology Group status score (2–3), squamous cell histology, and COPD were risk factors for mortality. The presence of COPD was a significant prognostic factor in univariate analysis (hazard ratio [HR], 1.402; p=0.037), but not in multivariate analysis (HR, 1.275; p=0.144). Subgroup analysis of 143 smokers showed that COPD was a significant prognostic factor on multivariate analysis (HR, 1.726; p=0.006). In 154 stage IV patients, COPD was also a prognostic factor in multivariate analysis (HR, 1.479; p=0.039). Conclusion: COPD had a negative impact on overall survival in the stage IV NSCLC and smoker NSCLC patients who underwent conventional chemotherapy. Keywords: non-small cell lung cancer, chronic obstructive pulmonary disease, smoker, overall survival

Sei Won Kim,1 Kyungdo Han,2 Shin Young Kim,3 Chan Kwon Park,3 Chin Kook Rhee,1 Hyoung Kyu Yoon3 1Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 2Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, 3Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Potential associations between oral health and respiratory disease, including chronic obstructive pulmonary disease (COPD), have been suggested in several studies. Among the indicators reflecting oral health, the number of natural teeth is an integrated and simple index to assess in the clinic. In this study, we examined the relationship between the number of natural teeth and airflow obstruction, which is a central feature of COPD.Methods: A total of 3,089 participants over 40 years, who underwent reliable spirometry and oral health assessments were selected from the Korean National Health and Nutrition Examination Survey 2012, a cross-sectional and nationally representative survey. Spirometry results were classified as normal, restrictive, or obstructive pattern. Total number and pairs of natural teeth were counted after excluding third molars.Results: After adjusting for other variables, such as age, body mass index, socioeconomic factors, and oral health factors, the group with airflow obstruction showed significantly fewer natural teeth than the other groups in males (P=0.014 and 0.008 for total number and total pairs of natural teeth, respectively). Compared with participants with full dentition, the adjusted odds ratio for airflow obstruction in males with fewer than 20 natural teeth was 4.18 (95% confidence interval: 2.06–8.49) and with fewer than 10 pairs of natural teeth was 4.74 (95% confidence interval: 2.34–9.62). However, there was no significant association between the total number or pairs of natural teeth and airflow obstruction after adjustment in females.Conclusions: Loss of natural teeth was significantly associated with the presence of airflow obstruction in males. Our finding suggests that the number of natural teeth could be one of the available indices for obstructive lung diseases, including COPD. Keywords: tooth loss, oral health, airflow obstruction, chronic obstructive pulmonary disease