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. Obstructive sleep apnea (OSA) is characterized by recurrent occlusion of the upper airway during sleep leading to chronic intermittent hypoxia (CIH). OSA is a highly prevalent sleep disorder affecting at least 3% to 7% of the adult population 1. OSA has been shown to be associated with morbidities including metabolic syndrome, systemic hypertension, pulmonary vascular disease, ischemic heart disease and congestive heart failure 2. In addition, OSA-related CIH has been suggested to affect tumor development and progression 3. OSA has been implicated in the increasing incidence of certain types of solid malignancies. In a Spanish cohort, increased overnight hypoxia as a surrogate of OSA severity was associated with increased cancer incidence in selected populations 4-6. Also, OSA was associated with increased cancer mortality in a community-based sample 7. The association between OSA and lung cancer has been evaluated. OSA-related CIH induced resistance to apoptosis and increased metastasis in lung cancer cells, in a manner related to hypoxia inducible factor 1α (HIF-1α) 8. The role of immune cells has been suggested as a potential mechanism linking OSA and cancer. Almendros et al. demonstrated that CIH induced changes in host immune responses are related to adverse cancer outcomes. CIH increases the mobilization of tumor-associated macrophages (TAMs) into tumors, and induces macrophages to transform from an anti-tumor phenotype (M1) to a tumor-promoting phenotype (M2) 9. Cyclooxygenase-2 inhibited IH-induced M2 polarization of TAMs and prevented IH-induced adverse tumor outcomes in a mouse model of sleep apnea 10. OSA-related CIH altered CD8 + T-cells in combination with changes in the tumor microenvironment that enhanced malignant tumor properties 11. Studies...

BackgroundMany studies have reported the prevalence of chronic obstructive pulmonary disease (COPD) and its effects and prognosis in patients with lung cancer, but few have considered quality of life and survival of patients with lung cancer according to severity of airway obstruction. This study investigated the presence of COPD and the severity of airway obstruction in patients with non-small cell lung cancer (NSCLC), and analyzed how these factors affected symptoms, quality of life, and prognosis.MethodsWe retrospectively reviewed the prospective lung cancer database of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017. We enrolled patients with advanced NSCLC and evaluated quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. We also estimated pulmonary function and analyzed survival data.ResultsOf the 337 patients with advanced NSCLC, 170 (50.5%) had COPD and 167 (49.5%) did not. Significant differences were observed in symptoms between the two groups. The COPD group complained of more symptoms, such as cough, sputum, and dyspnea, than those in the non-COPD group. The distribution according to the severity of obstruction in the COPD group was as follows: Grade 1 (FEV1 ≥ 80%) 35 patients (20.6%), Grade 2 (50% ≤ FEV1 < 80%) 103 patients (60.6%), Grade 3 (30% ≤ FEV1 < 50%) 24 patients (14.1%), and Grade 4 (FEV1 < 30%) 8 patients (4.7%). The presence of COPD did not affect overall quality of life in patients with NSCLC, but as the airway obstruction increased, physical function decreased, and fatigue and dyspnea were more frequent. The overall median survival of the COPD group was shorter than that of the non-COPD group (median survival, 224 vs. 339 days, p = 0.035).ConclusionsIn this study, a high prevalence of COPD was found among patients with advanced NSCLC, and COPD patients complained about various symptoms and had diminished quality of life in several sectors. Therefore, it is necessary to actively evaluate quality of life, lung function, and symptoms in patients with lung cancer and reflect them in the treatment and management plans of these patients.

BackgroundPrevious studies have reported that microalbuminuria is an independent risk factor for the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). For this reason, the clinical significance of DR in normoalbuminuric type 2 DM patients may be overlooked. The aim of this study was to investigate the prevalence of DR and predictors for DR in normoalbuminuric patients with type 2 DM.MethodsA total 310 patients with type 2 DM and normoalbuminuria, who were referred to the Department of Ophthalmology for screening of DR were included in this study. DR was clinically graded according to the International Clinical Diabetic Retinopathy guidelines. The urinary albumin excretion rate (UAER) was assessed via 24-hour urine collection and measured by immunoturbidimetric assay. Normoalbuminuria was defined as a UAER < 20 μg/min in 2 out of 3 consecutive tests taken within 2–3 months.ResultsDR of any grade was present in 64/310 (20.7 %) patients. Mild non-proliferative diabetic retinopathy (NPDR) was most prevalent in patients with DR of any grade (36/64, 56 %). The duration of diabetes (OR 1.01, 95 % CI, 1.01 – 1.02, p < 0.001), hemoglobin levels (OR 0.73, 95 % CI, 0.59 – 0.91, p = 0.004) and a higher tertile of UAER (OR 4.04, 95 % CI, 1.71 – 9.57, p = 0.001) had independently significant association with DR. NPDR as well as PDR was more prevalent in patients with higher tertile of UAER compared with those with lower tertile of UAER (NPDR, p = 0.002 and PDR, p = 0.027, respectively).ConclusionsOur findings suggest that patients with normoalbuminuric type 2 DM also require close monitoring for the early detection of DR, especially if they have a higher UAER, longer duration of diabetes, or lower hemoglobin levels.

PurposeTo investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC).Materials and MethodsFrom 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data.ResultsIn total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival.ConclusionDyspnea could be a significant prognostic factor in patients with NSCLC.

IntroductionThe detection of insomnia in patients with COPD is assumed to be significantly lower than the actual prevalence. In this study, we investigated the prevalence of insomnia and the relationship between insomnia and health status in patients with COPD using two fairly simple and straightforward questionnaires: COPD assessment test (CAT) and insomnia severity index (ISI).Patients and methodsA cross-sectional study was conducted using data from patients undergoing treatment for COPD at St Paul’s Hospital, The Catholic University of Korea, between December 2015 and August 2016. Patients were classified into three groups according to the ISI score: a “clinical insomnia” group (ISI≥15), a “subthreshold insomnia” group (ISI 8–15), and a “non-insomnia” group (ISI<8). Clinical parameters including past medical history, pulmonary function tests, and questionnaire data were collected and analyzed.ResultsA total of 192 patients were recruited, of which 25.0% were found to have clinical insomnia (ISI≥8). Insomnia severity was related to all CAT component items except for cough, and patients with higher CAT scores generally had more severe insomnia. Logistic regression analysis revealed that CAT score was significantly associated with insomnia in these patients (odds ratio, 1.23; 95% CI, 1.13–1.34; p<0.0001). CAT score was also a significant predictor of insomnia (area under receiver operating characteristic curve, 0.779; p<0.001). The optimal predictive cutoff value was a CAT score >14, giving a sensitivity and specificity of 66.7% and 71.5%, respectively.ConclusionCAT score was closely related to insomnia severity in patients with COPD. The use of CAT scores to assess for the presence and severity of insomnia in these patients may allow for better detection and management and improve clinical practice.