BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Carrier Proteins ; Enzyme-Linked Immunosorbent Assay ; Genetic Markers ; Humans ; Korea ; Lung Diseases ; Lung Neoplasms ; Mortality ; Plasma* ; Smoking ; Survival Rate ; Tretinoin

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.
Cadmium ; Cytokines ; Environmental Pollutants ; Epithelial Cells* ; Gene Expression ; Gene Expression Profiling ; Humans* ; Immunohistochemistry ; In Situ Hybridization ; Inflammation ; Lung ; Lung Neoplasms ; Pulmonary Disease, Chronic Obstructive ; RNA, Messenger ; Signal Transduction ; Smoke ; Smoking ; Succinate Dehydrogenase

Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.
Apoptosis ; Cadmium ; CCAAT-Enhancer-Binding Proteins ; Cell Cycle ; Down-Regulation ; Epithelial Cells* ; Humans* ; Inflammation* ; Lung Diseases ; Oxidative Stress ; Pulmonary Disease, Chronic Obstructive ; RNA, Small Interfering ; Signal Transduction ; Smoke ; Tobacco Products ; Transcriptional Activation ; Up-Regulation

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is sometimes complicated with pneumonia, but little is known about the risk factors that promote the development of pneumonia in COPD. These risk factors were evaluated in the present study. METHODS: The data of 324 patients with COPD from a prospective multi-center observational cohort with obstructive lung disease were evaluated retrospectively. To identify risk factors for the development of pneumonia in COPD, the clinical and radiological data at enrollment and the time to the first episode of pneumonia were analyzed by Cox proportional hazard analysis. RESULTS: The median follow-up time was 1,099 days and 28 patients (8.6%) developed pneumonia. The Cox analysis showed that post-bronchodilator forced expiratory volume in one second (FEV1, % of predicted) and the computed tomography (CT) emphysema extent (inspiratory V950) were independent risk factors for the development of pneumonia (post-bronchodilator FEV1: hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.94-1.00; p=0.048 and inspiratory V950: HR, 1.04; 95% CI, 1.01-1.07; p=0.01). CONCLUSION: Emphysema severity measured by CT and post-bronchodilator FEV1 are important risk factors for the development of pneumonia in COPD.
Cohort Studies ; Emphysema* ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Lung Diseases, Obstructive ; Lung* ; Pneumonia* ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive* ; Retrospective Studies ; Risk Factors ; Tomography, X-Ray Computed

BACKGROUND: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. METHODS: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. RESULTS: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. CONCLUSION: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.
Alternative Splicing* ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Exons ; Gene Fusion ; Lung ; Lung Neoplasms ; Multivariate Analysis ; Real-Time Polymerase Chain Reaction ; RNA* ; Sequence Analysis ; Sequence Analysis, RNA*

Percutaneous bronchial artery embolization and lung resection surgery have been effective for treatments of hemoptysis in patients with pulmonary arteriovenous malformation (PAVM). But, it has been little known about management for recurrent massive hemoptsis in patients with PAVM. It has been reported that Pumpless Extracoporeal Interventional Lung Assist (iLA) are effective for removal of hypercapnea in patient with acute respiratory failure. Here, we report a case of iLA support in a patient with PAVM complicating massive hemoptysis. A 38 year old man developed recurrent massive hemoptysis although interventions of bronchial artery embolization and lung resection surgery. The cause of recurrent hemoptysis was turned out PAVM. After a massive hemoptysis, the patient had severe hypercapnea and acidosis though mechanical ventilation and oxygenation. After iLA implantation, the hypercapnea was resolved and the clinical condition of the patient was improved, temporally. In conclusion, iLA may be a useful for bridge support in patients with prolonged massive hemoptysis.
Acidosis ; Arteriovenous Malformations* ; Bronchial Arteries ; Hemoptysis* ; Humans ; Lung* ; Oxygen ; Respiration, Artificial ; Respiratory Insufficiency

BACKGROUND: The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. METHODS: Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. RESULTS: From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. CONCLUSION: The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD.
Asthma ; Biomarkers ; Classification ; Cohort Studies* ; Genotype ; Humans ; Hypertension, Pulmonary ; Korea ; Longitudinal Studies ; Lung Diseases, Obstructive* ; Male ; Phenotype ; Population Characteristics ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive

Although many patients with severe emphysema have benefited from bronchoscopic lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema patients is scarce. Between July 2012 and March 2013, seven patients with advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They had severe dyspnea and poor lung function (Modified Medical Research Council dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV1], 0.59 L [19.0 % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves were inserted into the target lobe which was most hyperinflated and least perfused, and had no collateral ventilation with other lobes. Six patients showed clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale 1 and 4 patients did to scale 2 (P = 0.026). The median FEV1 increased from 0.59 to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring drainage) and one patient experienced slight hemoptysis; however, there were no other serious adverse events. BLVR is effective in Asian advanced emphysema patients, with noted clinical improvements in lung function and exercise capacity.
Aged ; Asian Continental Ancestry Group ; Bronchoscopy/*methods ; Forced Expiratory Volume ; Humans ; Lung/pathology/surgery ; Male ; Middle Aged ; Pneumonectomy/*methods ; Pulmonary Emphysema/*surgery ; Severity of Illness Index ; Tomography, X-Ray Computed ; Treatment Outcome

No abstract available.
Atrial Fibrillation* ; Heart Arrest* ; Propofol*

No abstract available.
Atrial Fibrillation* ; Heart Arrest* ; Propofol*