Background: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. Methods: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. Results: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). Conclusion Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

Background: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. Methods: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. Results: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). Conclusion Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

BACKGROUND: Although physical activity is known to be beneficial to lung function, few studies have been conducted to investigate the correlation between physical activity and lung function in dusty areas. Therefore, the purpose of this study is to investigate the correlation between physical activity and lung function in a Korean cohort including normal and COPD-diagnosed participants. METHODS: Data obtained from the COPD in dusty areas (CODA) cohort was analyzed for the following factors: lung function, symptoms, and information about physical activity. Information on physical activity was valuated using questionnaires, and participants were categorized into two groups: active and inactive. The evaluation of the mean lung function, modified Medical Research Council dyspnea grade scores, and COPD assessment test scores was done based on the participant physical activity using a general linear model after adjusting for age, sex, smoking status, pack-years, height, and weight. In addition, a stratification analysis was performed based on the smoking status and COPD. RESULTS: Physical activity had a correlation with high forced expiratory volume in 1 second (FEV₁) among CODA cohort (p=0.03). While the active group exhibited significantly higher FEV₁ compared to one exhibited by the inactive group among past smokers (p=0.02), no such correlation existed among current smokers. There was no significant difference observed in lung function after it was stratified by COPD. CONCLUSION: This study established a positive correlation between regular physical activity in dusty areas and lung function in participants.
Cohort Studies ; Dyspnea ; Forced Expiratory Volume ; Linear Models ; Lung ; Motor Activity ; Pulmonary Disease, Chronic Obstructive ; Respiratory Function Tests ; Smoke ; Smoking

BACKGROUND: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. METHODS: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years. RESULTS: We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION: This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.
Biomarkers ; DNA Methylation ; DNA ; Epigenomics ; Humans ; Lung Neoplasms ; Lung ; Methods ; Methylation ; Prognosis

BACKGROUND: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. METHODS: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years. RESULTS: We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

BACKGROUND: Although physical activity is known to be beneficial to lung function, few studies have been conducted to investigate the correlation between physical activity and lung function in dusty areas. Therefore, the purpose of this study is to investigate the correlation between physical activity and lung function in a Korean cohort including normal and COPD-diagnosed participants. METHODS: Data obtained from the COPD in dusty areas (CODA) cohort was analyzed for the following factors: lung function, symptoms, and information about physical activity. Information on physical activity was valuated using questionnaires, and participants were categorized into two groups: active and inactive. The evaluation of the mean lung function, modified Medical Research Council dyspnea grade scores, and COPD assessment test scores was done based on the participant physical activity using a general linear model after adjusting for age, sex, smoking status, pack-years, height, and weight. In addition, a stratification analysis was performed based on the smoking status and COPD. RESULTS: Physical activity had a correlation with high forced expiratory volume in 1 second (FEV₁) among CODA cohort (p=0.03). While the active group exhibited significantly higher FEV₁ compared to one exhibited by the inactive group among past smokers (p=0.02), no such correlation existed among current smokers. There was no significant difference observed in lung function after it was stratified by COPD. CONCLUSION This study established a positive correlation between regular physical activity in dusty areas and lung function in participants.

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: Pulmonary mucormycosis (PM) is an emerging infectious disease and a life-threatening infection with high mortality. The clinical outcomes of PM have not improved significantly over the last decade because early diagnosis of PM is difficult and antifungal agents show limited activity. We evaluated the clinical manifestations of PM in a Korean tertiary hospital and identified the role of transbronchial lung biopsy (TBLB) in diagnosing PM in patients admitted to an intensive care unit. METHODS: The medical records of adult patients (aged 16 years and older) who met the criteria for proven or probable PM in a Korean tertiary hospital were retrospectively reviewed from January 2003 to December 2013. The clinical features, computed tomographic findings, diagnostic methods, treatment, and outcomes in patients with PM were evaluated. RESULTS: Of the nine patients, four were male. The median age was 64 years (range, 12 to 73 years). PM was proven and probable in seven and two cases, respectively. Computed tomography findings of PM were unilateral involvement in eight cases (89%), consolidation in eight (89%), ground glass opacity in four (44%), and reverse halo sign in one (11%). Six of nine cases (67%) were diagnosed as PM from TBLB via portable bronchoscopy. There were no complications after TBLB. Mortality rate was 56% (five of nine cases). CONCLUSIONS: TBLB can be an easy and useful technique for diagnosing PM in the intensive care unit.
Adult ; Antifungal Agents ; Biopsy* ; Bronchoscopy ; Communicable Diseases, Emerging ; Critical Care* ; Early Diagnosis ; Glass ; Humans ; Intensive Care Units ; Lung* ; Male ; Medical Records ; Mortality ; Mucormycosis* ; Retrospective Studies ; Tertiary Care Centers

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: 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