Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial.

INTRODUCTION: To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer. MATERIALS AND METHODS: A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m2 with either docetaxel 60 mg/m2 (n = 71) or pemetrexed 500 mg/m2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles. RESULTS: Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm (P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm. CONCLUSION: In nonsquamous non-small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm.

Polymeric LabChip real-time PCR as a point-of-care-potential diagnostic tool for rapid detection of influenza A/H1N1 virus in human clinical specimens.

It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR) system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009. This LabChip real-time PCR system has several remarkable features: (1) It allows rapid quantitative analysis, requiring only 15 min to perform 30 cycles of real-time PCR. (2) It is portable, with a weight of only 5.5 kg. (3) The reaction cost is low, since it uses disposable plastic chips. (4) Its high efficiency is equivalent to that of commercially available tube-type real-time PCR systems. The developed disposable LabChip is an economic, heat-transferable, light-transparent, and easy-to-fabricate polymeric chip compared to conventional silicon- or glass-based labchip. In addition, our LabChip has large surface-to-volume ratios in micro channels that are required for overcoming time consumed for temperature control during real-time PCR. The efficiency of the LabChip real-time PCR system was confirmed using novel primer sets specifically targeted to the hemagglutinin (HA) gene of influenza A/H1N1 and clinical specimens. Eighty-five human clinical swab samples were tested using the LabChip real-time PCR. The results demonstrated 100% sensitivity and specificity, showing 72 positive and 13 negative cases. These results were identical to those from a tube-type real-time PCR system. This indicates that the novel LabChip real-time PCR may be an ultra-fast, quantitative, point-of-care-potential diagnostic tool for influenza A/H1N1 with a high sensitivity and specificity.

Increase in serum haptoglobin and apolipoprotein M in patients with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a common syndrome, which is associated with a number of medical problems that impact morbidity and mortality. Although the precise mechanisms that underlie these associations are not fully understood, previous studies have suggested that patients with OSA show elevations of several biomarkers that are associated with cardiovascular risk. This study was undertaken to identify serum proteins associated with OSA by using a proteomics technique and to examine changes in identified protein levels after continuous positive airway pressure treatment. The study participants consisted of 40 male patients (aged 40-49 years) with severe OSA and 34 male control subjects matched for age and body mass index. All subjects underwent polysomnography. Using a proteomics approach, we identified nine proteins that were differentially expressed in patients with severe OSA and controls. Three of these nine proteins, haptoglobin, paraoxonase-1 and apolipoprotein M, were quantified by using enzyme-linked immunosorbent assays, kinetic assays and by using Western blotting. Multiple regression analysis showed that haptoglobin and apolipoprotein M levels are independently related to apnoea-hypopnoea index (P < 0.01). A further study is required to determine the nature of associations between these identified proteins and OSA in a large population.

Lung cancer patients who are asymptomatic at diagnosis show favorable prognosis: a korean Lung Cancer Registry Study.

PURPOSE AND METHODS: The outcomes of lung cancer patients who were asymptomatic at diagnosis have never been reported as part of a large-scale study. A national survey of lung cancer in South Korea registered a total of 8788 patients diagnosed in 2005. We report the results herein, with an emphasis on the prognosis of the asymptomatic lung cancer patients. RESULTS: Adenocarcinoma was the most frequent (36.1%) histopathologic type, followed by squamous cell carcinoma (32.1%), large cell carcinoma (1.5%), and small cell carcinoma (13.5%). In most cases, lung cancer was detected with subjective symptoms, but 6.5% of cases had no symptoms indicative of lung cancer at the time of diagnosis. Compared to symptomatic patients, asymptomatic patients were younger, more often female, non-smokers, and more frequently presented with adenocarcinoma. Initial treatments were surgery (22.1%), radiation therapy (7.8%), chemo-radiation therapy (5.4%), and chemotherapy (38%), while 26.6% of patients were recorded to have supportive care only. Asymptomatic patients received surgery in 60.0% of cases, and they showed significantly longer survival times than symptomatic patients. Absence of symptoms at diagnosis significantly reduced the risk of death from non-small cell lung cancer, regardless of patient age, patient gender, stage at diagnosis, smoking history, or whether treatment was performed, but did not reduce the risk of death from small cell lung cancer. CONCLUSIONS: Adenocarcinoma has grown to be the leading histopathologic type of lung cancer in South Korea. Absence of symptom at diagnosis is a favorable prognostic factor for patients with non-small cell lung cancer.

Association of snoring with chronic bronchitis.

BACKGROUND: Snoring is more prevalent in patients with chronic bronchitis than in persons without it. Few studies have examined the effect of snoring on chronic bronchitis. We prospectively investigated the association between snoring and the incidence of chronic bronchitis. METHODS: The baseline study was conducted from June 25, 2001, to January 29, 2003. Members of the study cohort consisted of 5015 male and female Korean citizens aged 40 to 69 years at baseline who participated in a comprehensive health examination and on-site interviews at Korea University Ansan Hospital. Of these, 4270 participants (52% men and 48% women) entered the analysis for the first 2-year follow-up from April 17, 2003, to February 20, 2005, and those who met the same inclusion criteria remained in the analysis for a second 2-year follow-up period from February 21, 2005, to November 17, 2006. We collected information on snoring at baseline and identified incident cases of chronic bronchitis during a 4-year follow-up period. On the baseline questionnaire, we excluded participants who reported the presence of cough and sputum production on most days for at least 3 months a year. RESULTS: During 4 years of follow-up, we documented 314 cases of new-onset chronic bronchitis (27.1 cases per 1000 person-years). After taking into account age, smoking, and other risk factors for chronic bronchitis, the multivariate relative risks of chronic bronchitis were 1.25 (95% confidence interval [CI], 0.95-1.64) for persons snoring 5 times per week or less and 1.68 (95% CI, 1.17-2.42) for those snoring 6 to 7 times per week compared with never snorers (P for trend = .049). The analyses stratified by risk factors, including smoking, occupation, and body mass index, showed a stronger association among never smokers, house workers, and overweight persons. In analysis for the joint effect of smoking and snoring, the relative risks of chronic bronchitis were 1.39 (95% CI, 1.01-1.90) for nonsmoking and snoring, 2.31 (95% CI, 1.38-3.87) for smoking and never snoring, and 2.86 (95% CI, 1.91-4.27) for smoking and snoring compared with nonsmoking and never snoring. CONCLUSIONS: This prospective study observed that snoring is associated with chronic bronchitis. Our findings provide support for the hypothesis that snoring influences the development of chronic bronchitis.

Aspiration pneumonia due to polyethylene glycol-electrolyte solution (Golytely) treated by bronchoalveolar lavage.

Polyethylene glycol (PEG)-electrolyte solution (Golytely), is most commonly used for bowel preparation before colonoscopy, as well as for barium enema and colon surgery. In this case, a 70-year-old man developed ARDS following the administration of Golytely by mouth before a scheduled colonoscopy. Aspiration of PEG-electrolyte solution was suspected, and the patient was successfully treated by BAL. Therefore, early bronchoscopy and BAL should be considered as initial treatment for PEG aspiration, because removal of PEG is most important for managing the disease.

Clinical characteristics of acute pulmonary thromboembolism in Korea.

BACKGROUND: Acute pulmonary thromboembolism (APTE) remains an important cause of morbidity and mortality in Western countries. In Korea, both the incidence and the mortality rate of APTE were thought to be low compared to Western countries. We performed the present study to investigate the current status of APTE in Korea. METHODS: Eight hundred and eight registry patients with APTE were analyzed with respect to clinical symptoms and signs, the presence of underlying diseases or predisposing factors, diagnostic methods, treatment and clinical course. RESULTS: The most common risk factors were prolonged immobilization (22.9%), deep venous thrombosis (22.0%), a recent operation (19.2%), and cancer (15.8%). The most common symptoms were dyspnea (78.6%), and chest pain (26.9%). The most common abnormality on chest radiography was effusion. The overall mortality rate at 3 months was 11.0%. Multivariate logistic regression analysis demonstrated that increased mortality risk was independently associated with the following baseline factors: onset in hospital (OR 1.88; 95% CI 1.03-3.42; p=0.03), lung cancer (OR 9.20; 95% CI 1.96-43.27; p=0.005), tachycardia (OR 3.50; 95% CI 1.86-6.60; p=0.0001), cardiogenic shock (OR 6.74; 95% CI 2.73-16.64; p=0.0001), and cyanosis (OR 3.45; 95% CI 1.27-9.44; p=0.01). CONCLUSIONS: Some differences did exist for the risk factors, symptoms, chest X-ray findings, mortality rate and prognostic factors as compared with those for Western patients. These results can prove especially helpful in the diagnosis as well as for the treatment of patients with APTE.

Association of habitual snoring with glucose and insulin metabolism in nonobese Korean adult men.

Habitual snoring is associated with cardiovascular morbidity and mortality, and metabolic abnormalities such as impaired glucose homeostasis. Many studies were performed in obese Western populations. The purpose of this study was to examine the association of habitual snoring with glucose and insulin metabolism in nonobese Korean men who were free of diabetes and hypertension. A total of 2,719 men ages 40-69 years from the Korean Health and Genome Study participated in this study. Information of snoring frequency was obtained by a questionnaire and glucose and insulin levels during oral glucose tolerance test were measured. Repeated measures analysis of variance detected significant differences in the changing patterns of glucose and insulin levels at 1 hour and 2 hours between habitual snorers and nonhabitual snorers, whereas there were no significant differences in fasting blood glucose and insulin levels. Multivariate logistic regression analyses revealed that habitual snoring was independently associated with elevated 1-hour and 2-hour glucose levels and a 2-hour insulin level, respectively. The present data suggest that habitual snoring may affect glucose-insulin metabolism, independent of diabetes and hypertension, even in nonobese Korean middle-age men. Further prospective studies are needed to examine the causal relationship between habitual snoring and insulin resistance or glucose intolerance.

Relation of epidermal growth factor receptor expression to mucus hypersecretion in diffuse panbronchiolitis.

STUDY OBJECT: Diffuse panbronchiolitis (DPB) is a hypersecretory airway disease, and the mechanism of mucus hypersecretion in DPB is poorly understood. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression, and the degranulation of goblet cells is known to be mediated by neutrophilic elastase. In this study, we examined the relationship between EGFR expression in the bronchiolar epithelium with neutrophilic inflammation and mucus hypersecretion in the tissues of DPB patients. DESIGN: The tissue specimens of 13 DPB patients and 6 healthy control subjects were examined by alcian blue/periodic acid-Schiff (AB/PAS) staining for mucous glycoconjugates, and by immunohistochemical staining for MUC5AC, EGFR, tumor necrosis factor-alpha, and CD16 on neutrophils. RESULTS: Neutrophilic inflammation was significantly higher in the tissue of DPB patients than in that of control subjects (p = 0.002). In the bronchiolar epithelium, goblet cell metaplasia, by AB/PAS staining and mucin MUC5AC expression, was significantly higher than that in control subjects (p = 0.001 and p = 0.002, respectively). In addition, the morphometric quantification of intraluminal mucus secretion showed that the areas of the bronchiolar lumen occupied by mucus secretion were significantly increased in the tissue of DPB patients (p = 0.001), suggesting goblet cell degranulation. EGFR expression was observed in the bronchiolar epithelium of DPB patients, but not in that of control subjects. CONCLUSIONS: In DPB, we suggest that mucus hypersecretion due to goblet cell metaplasia is closely associated with neutrophilic inflammation and the expression of EGFR. The study also shows that intraluminal secretion due to the degranulation of goblet cells degranulation is related to neutrophilic inflammation.

Prevalence of sleep-disordered breathing in middle-aged Korean men and women.

With many epidemiologic studies made to establish the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea syndrome (OSAS) in Western countries, no such data have been reported in Korea. The purpose of this study was to examine the prevalence of SDB and OSAS, and their related factors in Korean adults aged 40-69 years. Among the total of 5,020 participants at the baseline examination of the Korean Health and Genome Study, a random sample of 457 men and women was studied with employment of overnight full polysomnography to determine the prevalence of SDB and OSAS. The prevalence of SDB (apnea-hypopnea index > or = 5) was 27% and 16% in men and women, respectively. When OSAS was defined by an apnea-hypopnea index > or = 5 plus excessive daytime sleepiness, its prevalence was 4.5% in men and 3.2% in women. Logistic regression analyses showed that sex, body mass index, and hypertension were closely associated with the risk of SDB. Our findings show that SDB is a common problem in the Korean adult population. Understanding and treatment of SDB may be essential in terms of intervention to reduce the risk of related medical problems.

Chromosomal aberrations in Korean nonsmall cell lung carcinomas: degenerate oligonucleotide primed polymerase chain reaction comparative genomic hybridization studies.

Chromosomal aberrations were investigated in 48 Korean nonsmall cell carcinomas of the lung (NSCLC), by degenerate oligonucleotide primed polymerase chain reaction comparative genomic hybridization. These included 16 adenocarcinomas, 27 squamous cell carcinomas (SCCs), and 5 large-cell carcinomas. The common sites of copy number increases were 3q26 approximately qter (23 cases, 48%); 8q23 approximately qter (46%); 20q13.1 (42%); 1q42 approximately qter (38%); 3q25 (38%); 21q22 (38%); and 22q13 (38%). DNA amplification was identified in 19 carcinomas (40%), and the frequent sites of amplification were 8q24 (seven cases), 3q26 (seven cases), and 3q27 (seven cases). The frequently under-represented chromosomal regions were Yq (38%), 4q25 approximately q26 (23%), and 4q31 (23%). In particular, gains of 3q26 approximately qter (74%), 15q (56%), and 19q (59%) and loss of 13q22 approximately q31 (26%) were more frequently detected in SCCs of the lung. These nonrandom aberrations can serve as starting points for the identification of potential oncogenes/tumor suppressor genes related to the tumorigenesis of Korean NSCLC.