Associations among sleep-disordered breathing, sleep quality, and lung cancer in Korean patients.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Time delays and risk factors in the management of patients with active pulmonary tuberculosis: nationwide cohort study.

Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0-40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639-2.687; p < 0.001] and heavy alcohol intake (adjusted OR 1.505; 95% CI 1.187-1.907; p < 0.001). The median healthcare delay was 5.0 (1.0-14.0) days. A longer healthcare delay was associated with malignancy (adjusted OR 1.351; 95% CI 1.069-1.709; p = 0.012), autoimmune disease (adjusted OR 2.445; 95% CI 1.295-4.617; p = 0.006), and low bacterial burden manifested as an acid-fast bacillus smear-negative and tuberculosis polymerase chain reaction-negative status (adjusted OR 1.316; 95% CI 1.104-1.569; p = 0.002). Active case-finding programmes need to focus on patients with heavy alcoholism or neuropsychiatric diseases. To ensure early PTB detection, healthcare providers must carefully monitor patients with malignancy, autoimmune disease, or a high index of suspicion for PTB.

Impacts of the COVID-19 pandemic on sleep center operations and sleep apnea treatment in Korea: A multicenter survey.

ABSTRACT: 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.

Reflux esophagitis in patients with chronic obstructive pulmonary disease.

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.

Histiocytic pleural effusion: the strong clue to malignancy.

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.

Independent association of serum uric acid levels with arterial stiffness in the absence of established cardiovascular disorders.

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 <40 mg/dL; fasting glucose ≥126 mg/dL; body mass index ≥25.0 kg/m2 ; current smoking; and history of medication for hypertension, diabetes, and dyslipidemia. Subjects were stratified into four groups based on the quartiles of their SUA levels. RESULTS: Mean baPWV was significantly different in all groups: group I, 1320 ± 195 cm/s; group II, 1336 ± 195 cm/s; group III, 1404 ± 199 cm/s; and group IV, 1483 ± 248 cm/s (P < .001). SUA levels were significantly correlated with baPWV (r = .364) (P < .001). Multivariate linear regression analysis showed that SUA (ß: 32.93; 95% confidence interval [CI]: 18.99-54.87), together with age (ß: 11.44; 95% CI: 9.36-13.53) and systolic BP (ß: 8.98; 95% CI: 6.80-11.16), was significantly associated with baPWV (P < .001). CONCLUSIONS: High SUA levels have an independent association with increased arterial stiffness even in subjects without established CV disorders.

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

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.

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

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.

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

Purpose/Aim of the study: 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).Meterials and Methods: 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% O2 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.Results: 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-ß (TGF-ß) 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)-1ß 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.Conclusions: 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.

Normobaric hyperoxia inhibits the progression of lung cancer by inducing apoptosis.

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.

Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions.

BACKGROUND: We aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible. METHODS: This was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield. RESULTS: We included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76-13.72; p=0.002). CONCLUSION: The presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.

Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer.

PURPOSE: To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 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. RESULTS: In 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. CONCLUSION: Dyspnea could be a significant prognostic factor in patients with NSCLC.

The apoptotic effect of simvastatin via the upregulation of BIM in nonsmall cell lung cancer cells.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Serious Complications after Self-expandable Metallic Stent Insertion in a Patient with Malignant Lymphoma.

An 18-year-old woman was evaluated for a chronic productive cough and dyspnea. She was subsequently diagnosed with mediastinal non-Hodgkin lymphoma (NHL). A covered self-expandable metallic stent (SEMS) was implanted to relieve narrowing in for both main bronchi. The NHL went into complete remission after six chemotherapy cycles, but atelectasis developed in the left lower lobe 18 months after SEMS insertion. The left main bronchus was completely occluded by granulation tissue. However, the right main bronchus and intermedius bronchus were patent. Granulation tissue was observed adjacent to the SEMS. The granulation tissue and the SEMS were excised, and a silicone stent was successfully implanted using a rigid bronchoscope. SEMS is advantageous owing to its easy implantation, but there are considerable potential complications such as severe reactive granulation, stent rupture, and ventilation failure in serious cases. Therefore, SEMS should be avoided whenever possible in patients with benign airway disease. This case highlights that SEMS implantation should be avoided even in malignant airway obstruction cases if the underlying malignancy is curable.

Efficacy of team-based financial incentives for smoking cessation in the workplace.

Worksite smoking cessation programs offer accessibility of the target population, availability of occupational health support, and the potential for peer pressure and peer support. The purpose of this study was to identify the efficacy of the financial incentives given to various teams in the workplace. St. Paul's Hospital's employees were enrolled. Each team of employees consisted of smoking participants and non-smoking fellow workers from the same department. The financial incentive of 50000 won (about $45) was rewarded to the team for each successful participant-not to individual members-after the first week and then after one month. If the smokers in the team remained abstinent for a longer time period, the team was given an incentive of 100000 won for each successful participant after 3 and 6 months. A total 28 smoking participants and 6 teams were enrolled. Self-reported abstinence rates validated by urinary cotinine test at 3, 6, and 12 months after the initial cessation were 61%, 54%, and 50%, respectively. Smokers with high nicotine dependence scores or those who began participation 1 month after enrollment initiation had a lower abstinence rate at 3 months, but not at 6 and 12 months. Participants who succeeded at smoking cessation at 12 months were more likely to be older and have a longer smoking duration history. The financial incentives given to teams could be promising and effective to improve long-term rates of smoking cessation. This approach could use peer pressure and peer support in the workplace over a longer period.

The associations between anthropometric indices and obstructive sleep apnea in a Korean population.

BACKGROUND: Obesity is a major risk factor for the development of obstructive sleep apnea (OSA). Although clinical and epidemiological studies have shown that OSA and obesity are strongly associated, few Asian studies have examined the associations between anthropometric obesity indices and OSA, especially in the Korean population. The purpose of this study was to evaluate the influence of anthropometric obesity indices on OSA in a Korean population. METHODS: Anthropometric indices, including neck circumference, waist circumference, and body mass index, were assessed in 383 consecutive subjects with suspected OSA. RESULTS: Of the 383 subjects assessed, 316 (82.5%) were diagnosed with OSA. Neck circumference (r = 0.518), waist circumference (r = 0.570), and body mass index (r = 0.512) were correlated with the apnea-hypopnea index (p<0.001, for all). After adjusting for age, sex, alcohol consumption, and smoking, a logistic regression model showed that neck circumference [odds ratio (OR), 1.414; p<0.001)], waist circumference (OR, 1.114; p<0.001), and body mass index (OR, 1.364; p<0.001) were associated with OSA. The linear regression model showed that neck circumference (ß = 3.748, p<0.001), waist circumference (ß = 1.272, p<0.001), and body mass index (ß = 3.082, p<0.001) were associated with apnea-hypopnea index. The cut-off values for predicting OSA were determined as 34.5 cm for neck circumference, 76.5 cm for waist circumference, and 23.05 kg/m2 for body mass index for females, and 38.75 cm for neck circumference, 88.5 cm for waist circumference, and 24.95 kg/m2 for body mass index for males. CONCLUSION: Increased anthropometric indices were significantly associated with the presence and severity of OSA in a Korean population. In addition, this study demonstrated the cut-off values for body mass index, waist circumference, and neck circumference for increased OSA risk.

A case of pneumomediastinum and parapneumonic effusions following pharyngeal perforation caused by shouting.

Spontaneous pneumomediastinum is an uncommon disorder, and usually affects young men and has a benign course. Common triggers are asthma, the smoking of illicit drugs, the Valsalva maneuver, and respiratory infections. Most cases are usually due to alveolar rupture into the pulmonary interstitium caused by excess pressure. The air dissects to the hilum along the peribronchovascular sheaths and spreads into the mediastinum. However, pneumomediastinum following pharyngeal perforation is very rare, and has only been reported in relation to dental procedures, head and neck surgery, or trauma. We report a case of pneumomediastinum that developed in a 43-year-old patient with pharyngeal perforation after shouting. His course was complicated by mediastinitis and parapneumonic effusions.

A multicenter phase II study of belotecan, a new camptothecin analogue, in elderly patients with previously untreated, extensive-stage small cell lung cancer.

PURPOSE: 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). METHODS: 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/m(2)/day for 5 consecutive days every 3 weeks. RESULTS: 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. CONCLUSION: 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.

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery.

INTRODUCTION: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice. METHODS: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined. RESULTS: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-ß and c-KIT in imatinib or nilotinib group were significantly lower than LPS group. CONCLUSIONS: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

Protective effect of pravastatin on lipopolysaccharide-induced acute lung injury during neutropenia recovery in mice.

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-1ß, 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-ß 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.