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Intermittent hypoxia and sleep fragmentation, two main features of sleep-disordered breathing (SDB), have been shown to increase the aggressiveness of lung cancer, mainly in animal and in vitro studies. However, the association between SDB and lung cancer has not been well described in human studies. In this study, we investigated the associations among SDB, sleep quality, and lung cancer in Korean patients.Patients with histologically diagnosed lung cancer performed a home sleep apnea test. Sleep questionnaires including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index, and Pittsburgh Sleep Quality Index were also administered. Clinical information related to lung cancer was collected during the study.Sixty-nine patients were enrolled, 31 of whom were poor sleepers. The overall prevalence of SDB was 57% and that of moderate to severe SDB was 27%. Underlying chronic obstructive pulmonary disease (COPD) and smoking history were significantly more frequent in patients with moderate to severe SDB compared to patients without or with mild SDB. No significant differences were observed in the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), or time with oxygen saturation 90% (T90) according to cancer cell types, mutations, stages, and survival. However, small-cell lung cancer patients showed a trend toward higher AHI, ODI, and T90 values.The prevalence of SDB and proportion of poor sleepers were high in Korean patients with lung cancer. Paying more attention to sleep status may be helpful for patients with COPD, a smoking history, and small-cell lung cancer.

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 (P = 0.590). The prevalence of GERD did not correlate with OSA severity (P = 0.474). Patients with OSA with GERD had higher Stanford Sleepiness Scale (P = 0.004), Epworth Sleepiness Scale (P = 0.001), and depression (P < 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. (J Neurogastroenterol Motil 2021;27:215-222)

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.

Jee Youn Oh,1 Sung-Soon Lee,2 Hyung Woo Kim,3 Jinsoo Min,4 Yousang Ko,5 Hyeon-Kyoung Koo,2 Yun-Jeong Jeong,6 Hyeon Hui Kang,7 Ji Young Kang,8 Ju Sang Kim,3 Jae Seuk Park,9 Yunhyung Kwon,10 Jiyeon Yang,10 Jiyeon Han,10 You Jin Jang,10 Min Ki Lee,11 Yangjin Jegal,12 Young-Chul Kim,13 Yun Seong Kim14 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; 7Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 9Division of Pulmonary Medicine, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea; 10Division of Tuberculosis Prevention and Control, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea; 11Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Pusan, Republic of Korea; 12Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, Republic of Korea; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Republic of Korea; 14Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of KoreaCorrespondence: Sung-Soon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea, Tel +82-10-7173-6575, Fax +82-2-2626-1166, Email sungsoonlee@gmail.comPurpose: Bronchoscopy is widely used for microbiological diagnosis of patients with minimal sputum production. However, the usefulness of bronchoscopy in patient groups who benefit from subsequent microbiological confirmation has not been established.Patients and Methods: We retrospectively analyzed Korean tuberculosis (TB) cohort data from September 2018 to October 2019 to evaluate the usefulness of bronchoscopy in patients with microbiologically negative pulmonary TB (based on initial sputum polymerase chain reaction and culture results). The primary outcome was the proportion of microbiological diagnoses made after bronchoscopy. Secondary outcomes were the predictors of microbiological confirmation and the percentage of additional resistance detection after bronchoscopy.Results: A total of 5194 patients were diagnosed with pulmonary TB, 937 of whom were microbiologically negative for pulmonary TB based on the initial sputum findings. Of these, 319 patients underwent bronchoscopy, and further microbiological confirmation was achieved in 157 (49.1%) patients. The predictors of microbiological confirmation after bronchoscopy were age > 65 years, female sex, and low body mass index (BMI). The rate of additional resistance detection was 10.5% (multidrug resistant/rifampin-resistant 3.8%; isoniazid-resistant 5.7%).Conclusion: Bronchoscopy can be used for the detection of resistant pathogens. Bronchoscopy should be considered for microbiologically negative pulmonary TB in women aged > 65 years and with low BMI for subsequent microbiological confirmation.Keywords: tuberculosis, pulmonary, bronchoscopy, cohort studies

Background The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea. Methods We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as ‘before-pandemic’ and ‘during-pandemic’ based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment. Results Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715–1.094). Conclusion The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic’s impact on the national TB control project., Graphical Abstract

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

Purpose: Obstructive sleep apnea (OSA) is known to be associated with upper airway collapse during sleep. However, OSA has also been suggested to have effects on the lower airway. This study examined the association between pulmonary function test (PFT) results and OSA according to the severity of OSA and the presence of obesity. Changes in PFT results with body position (sitting vs. supine) were also analyzed. Methods: A total of 46 patients who were diagnosed with OSA were included in this study. Patients were grouped according to the severity of OSA and the presence of obesity. Results: Obese, severe OSA patients tended to show poorer pulmonary function than non-obese, mild-to-moderate OSA patients. Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC; sitting), peak expiratory flow (PEF; sitting), and forced expiratory flow during the middle half of the FVC (FEF25-75; supine) were significantly lower in the severe OSA group than the mild-to-moderate OSA group (P=0.020, P=0.044, and P=0.042, respectively). Positional change from sitting to the supine position significantly reduced pulmonary function in the total OSA patient population. The effect of body position on PFT results was greater in non-obese, mild-to-moderate OSA patients. FEF25-75 in the sitting position was still significantly related to the apnea-hypopnea index in OSA patients after adjusting for other factors (P=0.048). Conclusions: This study indicated that relationships exist between lower airway function, body position, and OSA. The PFT is a simple test that can provide useful information about the upper and lower airways in OSA patients.

Background There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. Methods In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. Results Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology. Conclusions The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

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.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, FiOThe 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.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.

BACKGROUND The impact of serum uric acid (SUA) on atherosclerosis has been suspected to be epiphenomenal owing to its close relationship with metabolic abnormalities. The aim of the present study was to evaluate the association between SUA levels and arterial stiffness in the absence of established cardiovascular (CV) disorders. METHODS The relationship between SUA levels and brachial-ankle pulse wave velocity (baPWV) was examined in 353 asymptomatic adults (57 ± 8 years, 11.9% men) without established CV disorders defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥ 90 mmHg; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol

Purpose Work-related asthma (WRA) occupies about 10%-30% of all asthma cases. Among 2 subtypes of WRA (occupational asthma [OA] and work-exacerbated asthma [WEA]), the rate of WEA has been reported to increase recently. WRA is described as having worse characteristics than non-WRA (NWRA), while WEA is known to show similar severity to OA in terms of symptoms and exacerbations. However, these data were mainly based on indirect surveys. Ulsan is a highly industrialized city in Korea; therefore, it is estimated to have a high incidence of WRA. This study aimed to identify the characteristics of WRA in the city. Methods This was a prospective asthma cohort study of individuals diagnosed with asthma and treated at Ulsan University Hospital between Jan 2015 and Dec 2016. Baseline characteristics and work-related inquiry (9 questionnaires) were investigated at enrollment. Various severity indices and job change were then investigated for the longitudinal analysis at 12 months after enrollment. Results In total, 217 asthma patients completed the study. WRA accounted for 17% (36/217), with an equal number of WEA and OA (18 patients each). Before the work-related survey, only 33% (n = 12) of WRA patients (22% [4/18] of WEA and 44% [8/18] of OA) were diagnosed with WRA by the attending physicians. Compared to the NWRA group and the OA subgroup, the WEA subgroup had more outpatient visits, more oral corticosteroids prescriptions, and trends of low asthma control test scores and severe asthma. The rate of job change was markedly lower in the WEA subgroup than in the OA subgroup (20% vs. 5%). Conclusions The overall prevalence of WRA (17%) was similar to those of previous studies, but the share of WEA was high (50% of WRA). WEA was more severe than OA or NWRA. The possible reason for this severity is ongoing workplace exposure.

STUDY OBJECTIVES: To evaluate the readability, content, and quality of internet information about obstructive sleep apnea (OSA). METHODS: Three major search engines (Google, Yahoo, and Bing) were used to retrieve the first 200 hits for the term “sleep apnea.” The website contents were assessed using established guidelines, while the website quality was evaluated using the validated DISCERN instrument and Journal of the American Medical Association benchmarks. RESULTS: In total, 243 websites met the inclusion criteria for this study. The websites were divided into five categories: scientific resource, foundation, news/ media report, commercial website, and personal commentary. The mean Flesch-Kincaid grade level, which indicated the readability of the websites, was 7.5. The quality of most websites was poor, with news/media reports and commercial websites exhibiting poorer quality than the others. The Health On the Net (HON) code, which certifies the reliability and credibility of online content regarding human health, was applied only to 14.3% websites; the reliability of all these websites was poor. The content score for the diagnosis and management of OSA was lower for news/media reports and commercial websites than for scientific resources. News/media reports exhibited the worst content scores. CONCLUSIONS: Our findings suggest that most online health resources regarding OSA are not reliable and are inaccurate. Health care providers should be aware of the high variability in online information concerning OSA. COMMENTARY: A commentary on this article appears in this issue on page 1643. CITATION: Lee J, Ban WH, Park HK, Na E, Kim SK, Kang HH, Lee SH. Accuracy and reliability of internet resources providing information on obstructive sleep apnea. J Clin Sleep Med. 2018;14(10):1717–1723.

Hypoxia is a critical characteristic of solid tumors with respect to cancer cell survival, angiogenesis, and metastasis. Hyperoxic treatment has been attempted to reverse hypoxia by enhancing the amount of dissolved oxygen in the plasma. In this study, we evaluated the effects of normobaric hyperoxia on the progression of lung cancer to determine whether oxygen toxicity can be used in cancer therapy. Following a tail vein injection of the Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric hyperoxia/normoxia cycle for two weeks. In addition, A549 lung cancer cells were incubated in a normobaric hyperoxia chamber for a 24-h period. As a result, the size and number of tumors in the lung decreased significantly with exposure to normobaric hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric hyperoxia and the normal control group exposed to normobaric hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric hyperoxia in cancer cells. A549 cells exposed to normobaric hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2 mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric hyperoxia in inhibiting lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-tumor effect of normobaric hyperoxia may due to the increased reactive oxygen species activity and apoptosis, which is related to the mitogen-activated protein kinase pathway. Impact statement Normobaric hyperoxia (NBO) is a feasible therapy for cancer with a low complication rate. Although NBO may be beneficial in cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.

The coronavirus disease-2019 (COVID-19) pandemic has not only changed the lives of people around the world but also affected all areas of the healthcare system, including sleep medicine. However, no studies in Korea have investigated the status of domestic sleep centers and their challenges during the pandemic.An online survey was performed from December 2020 to January 2021. Hospitals that belonged to sleep-related academic societies and were considered well managed were included in this survey. The questionnaire focused on changes in sleep center operations, infection control policies, and patient treatment since the start of the COVID-19 pandemic. Telemedicine and future directions for sleep medicine services were also investigated.Of the 20 sleep centers that responded, 80% were at university hospitals with more than 500 inpatient beds. During the third wave of the COVID-19 pandemic in Korea (November-December 2020), the routine operating schedule of the sleep study room was reduced in 30% of the sleep centers compared to November-December 2019 (before COVID-19). The number of type 1 polysomnographies performed decreased in 85% of the sleep centers. In contrast, in-lab positive airway pressure (PAP) titrations decreased in 40%, remained unchanged in 35%, and increased in 25%. With respect to prescriptions, 30% of the sleep centers increased the number of prescriptions for auto-titrating continuous PAP. However, 60% of the sleep centers reported no change in the rate of fixed continuous PAP and auto-titrating continuous PAP prescriptions. All sleep centers that participated in this survey agreed that the need for documented infection control regulations will continue after the COVID-19 pandemic. Since the beginning of the pandemic, 30% of the centers have tried telemedicine. However, respondents expressed concern about telemedicine, citing a number of practical issues.Compared to countries where the COVID-19 pandemic was severe, Korea had less impact of COVID-19 on the sleep center operations and sleep apnea treatment. Infection and quality control in the sleep study room are important and inevitable issues, and regulation within each institution is necessary. Further research and discussion are needed regarding telemedicine and home sleep apnea test in Korea.

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.

Background/Aims: This study evaluated the validity and reliability of the Ko rean 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 par ticipants. 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 sta tistically significant positive correlation with that of the MNWS-K (Pearson’s correlation coefficient, 0.768; p < 0.01). Additionally, we performed linear regres sion 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 WS WS-K was < 0.001. Conclusions: The WSWS-K had satisfactory validity and reliability. The WS WS-K can be used with acceptable validity and reliability in research and clini cal evaluation of Korean smokers.

Introduction: Obstructive sleep apnea (OSA) is highly common among patients with idiopathic pulmonary fibrosis. OSA causes chronic intermittent hypoxia (CIH) during sleep. We aimed to investigate the effect of CIH on bleomycin-induced pulmonary fibrosis in mice and to explore putative mechanisms. Methods: C57/BL6 mice were divided into four groups and then exposed to control conditions (room air) or CIH for 2 weeks prior to the intratracheal injection of bleomycin. After bleomycin instillation, mice were exposed to CIH or room air for 4 weeks. Fibrosis was evaluated by Masson’s trichrome stain and hydroxyproline assay. The mRNA expressions or protein levels of fibrosis-related genes were measured by real-time PCR and western blot in lung tissue, respectively. Results: Masson staining showed that CIH led to scattered fibrotic changes in alveolar structure and substantive fibrotic tissue dominantly situated in the perivascular space. In bleomycin-treated group, CIH compared to control increased hydroxyproline (p Conclusion: Following bleomycin-induced lung injury, CIH might exacerbate the progression of pulmonary fibrosis via TGF-β/Smad/Snail signaling.

Woo Ho Ban,1 Hyonsoo Joo,1 Jeong Uk Lim,1 Hyeon Hui Kang,2 Hwa Sik Moon,2 Sang Haak Lee2 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Introduction: The 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 methods: A 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 (ISI14, giving a sensitivity and specificity of 66.7% and 71.5%, respectively. Conclusion: CAT 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. Keywords: chronic obstructive, maintenance disorders, pulmonary disease, sleep initiation

Objectives We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. Methods Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. Results Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. Conclusions This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

Statins are known to have pleiotropic effects that induce cell death in certain cancer cells. BIM is a member of the bcl-2 gene family, which promotes apoptotic cell death. This study investigated the hypothesis that simvastatin has pro-apoptotic effects in epidermal growth factor receptor (EGFR)-mutated lung cancer cell lines via the upregulation of the expression of the BIM protein.The cytotoxic effects of simvastatin on gefitinib-sensitive (HCC827, E716-A750del) and -resistant (H1975, T790M + L858R) nonsmall cell lung cancer (NSCLC) cells were compared. Cell proliferation and expression of apoptosis-related and EGFR downstream signaling proteins were evaluated. Expression of BIM was compared in H1975 cells after treatment with simvastatin or gefitinib. SiRNA-mediated BIM depletion was performed to confirm whether the cytotoxicity of simvastatin was mediated by the expression of BIM.H1975 cells showed significantly reduced viability compared with HCC827 cells after treatment with simvastatin (2 μM) for 48 hours. In simvastatin-treated H1975 cells, expression of pro-apoptotic proteins was increased and the phosphorylation of ERK 1/2 (p-ERK 1/2) was reduced. Expression of BIM was suppressed by gefitinib (1 μM) treatment in H1975 cells, but it was significantly increased by treatment with simvastatin. BIM depletion by siRNA transfection enhanced the viability of H1975 cells that received simvastatin treatment and increased their expression of anti-apoptotic proteins.Simvastatin restored the expression of BIM to induce apoptotic cell death in NSCLC cells harboring an EGFR-resistant mutation. Our study suggests the potential utility of simvastatin as a BIM-targeted treatment for NSCLC.

Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model. Inflammatory and oxidative stress markers, TLR4, MyD88, Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-β (TRIF), I-κB, NF-κB, p38 MAPK, c-JNK, and ERK activation, were measured in the serum and liver. As a result, α1(I)-collagen mRNA was significantly higher in DIO mice exposed to CIH than in the control groups. CIH mice exhibited liver fibrosis and significantly higher protein expression of TLR4, MyD88, phosphorylated (phospho-) I-κB, and phospho-ERK1/2 activation in the liver, and higher expression of NF-κB than that in the controls. TRIF, p38 MAPK, and JNK activation did not differ significantly between groups. We conclude that CIH in DIO mice leads to liver fibrosis via TLR4/MyD88/MAPK/NF-kB signaling pathways.

Belotecan is a new camptothecin analogue and a potent topoisomerase I inhibitor. The aim of this phase II study was to investigate the efficacy and toxicity of belotecan in previously untreated elderly patients with small cell lung cancer (SCLC). A total of 26 patients, aged ≥65 years, with previously untreated, extensive-stage SCLC were enrolled in the study. Belotecan was administered by daily intravenous infusion at 0.5 mg/m2/day for 5 consecutive days every 3 weeks. The overall response rate and disease control rate of chemotherapy on an intention-to-treat basis were 35 and 54 %, respectively. The median overall survival was 6.4 months, and the median time to progression was 2.8 months. The most common toxicity was hematologic. Grade 3 or 4 neutropenia occurred in 80.8 % of patients, and grade 3 or 4 thrombocytopenia in 15.3 %. Non-hematologic toxic effects of grade 3 or 4 were uncommon. Belotecan had modest efficacy and well-tolerated toxicity in previously untreated, elderly SCLC patients. Single belotecan could be a promising treatment option, considering its lower toxicity in elderly patients who are unsuitable candidates for platinum plus etoposide chemotherapy.

Although neutropenia recovery is associated with deterioration of preexisting acute lung injury (ALI), there are few reports of the preventive strategies. Statins have been found to attenuate inflammatory responses in murine models of lipopolysaccharide (LPS)-induced ALI. The aim of this study was to determine whether pravastatin could attenuate ALI during neutropenia recovery in mice. Cyclophosphamide was administered to mice to induce neutropenia. Mice were given intratracheal LPS 7 days after cyclophosphamide administration, after which pravastatin was administered by intraperitoneal injection. In order to study the effects of pravastatin, mice were killed on day 5. Pravastatin attenuated the pulmonary edema and histopathological changes of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-1β, IL-6, and MPO in BAL fluids were also effectively inhibited by pravastatin. The expression levels of Toll-like receptor 4, nuclear factor kappa B, tumor growth factor-β and matrix metalloproteinase-9 were significantly reduced by pravastatin. Taken together, pravastatin significantly attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the potential of pravastatin in the treatment of ALI during neutropenia recovery.

Introduction: Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. Inflammatory processes and oxidative stress are known to play a key role in the development of metabolic complications induced by CIH. The purpose of this study was to investigate the proteins related to inflammation in liver subjected to CIH with diet-induced obesity (DIO). Methods: Eight-week old male C57BL/6J mice were fed a high fat or regular diet for 12 weeks and then exposed to CIH or room air for 4 weeks. At the end of the exposure, we examined several genes including myeloid differentiation primary response protein 88 (MyD88), Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-β (TRIF), I kappa B (I-κB), nuclear factor kappa B (NF-κB), Toll-like receptor 4 (TLR4), p38 MAP kinase (MAPK), JNK and ERK activation in liver tissue. Results: There was a significant reduction in body weight in DIO mice exposed to CIH steadily through 4 weeks compared with DIO group exposed to room air (P Conclusion: Exposure to CIH in DIO mice by simulating OSA patients leads to hepatic inflammation via TLR4/MyD88/MAPK/NF-kB signaling pathways.