Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease

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.

Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease

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.

Correlation between Physical Activity and Lung Function in Dusty Areas: Results from the Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) Cohort / 결핵및호흡기질환

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.

Identification of Serial DNA Methylation Changes in the Blood Samples of Patients with Lung Cancer / 결핵및호흡기질환

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.

Correlation between Physical Activity and Lung Function in Dusty Areas: Results from the Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) Cohort / 결핵

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.

Identification of Serial DNA Methylation Changes in the Blood Samples of Patients with Lung Cancer / 결핵

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.

Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer

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.

The Role of Transbronchial Lung Biopsy in Diagnosing Pulmonary Mucormycosis in a Critical Care Unit / 대한중환자의학회지

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.

Cadmium-induced ER stress and inflammation are mediated through C/EBP–DDIT3 signaling in human bronchial epithelial cells

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.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells / 결핵및호흡기질환

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.

The Role of Transbronchial Lung Biopsy in Diagnosing Pulmonary Mucormycosis in a Critical Care Unit / 대한구급학회지

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.

Identification of Alternative Splicing and Fusion Transcripts in Non-Small Cell Lung Cancer by RNA Sequencing / 결핵및호흡기질환

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.

Implications of Emphysema and Lung Function for the Development of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

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.

Therapeutic effects of adipose-derived stem cells pretreated with pioglitazone in an emphysema mouse model

There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice. We also investigated the mechanisms of action of pioglitazone-pretreated ASCs. Pioglitazone-pretreated ASCs had a more potent therapeutic effect than non-pretreated ASCs in the repair of both elastase-induced and smoke-induced emphysema models (mean linear intercept, 78.1±2.5 μm vs 83.2±2.6 μm in elastase models and 75.6±1.4 μm vs 80.5±3.2 μm in smoke models, P<0.05). Furthermore, we showed that pioglitazone-pretreated ASCs increased vascular endothelial growth factor (VEGF) production both in vitro and in mouse lungs in the smoke-induced emphysema model. Pioglitazone-pretreated ASCs may have more potent therapeutic effects than non-pretreated ASCs in emphysema mouse models.

Respiratory Failure Induced by Severe Hypothyroidism in a Korean Woman

A 76-year-old Korean woman visited to emergency room because of respiratory arrest and admitted to intensive care unit of the hospital. Severe hypothyroidism was diagnosed after repeated failure of weaning mechanical ventilator. Respiratory arrest and weaning failures were considered to be associated with hypoventilation due to hypothyroidism. She was recovered and weaned from mechanical ventilation after replacement of thyroid hormone. Severe hypothyroidism may be a cause of respiratory failure or weaning failure.

Empyema caused by Clostridium perfringens / 영남의대학술지

Pleuropulmonary diseases caused by Clostridial species infections are rare, but have a mortality rate of up to 30%. Furthermore, older people are at greater risk of developing invasive clostridium infections, and the majority of reported cases of clostridium empyema have been attributed to iatrogenic trauma or aspiration. The authors report a case of spontaneous empyema caused by Clostridium perfringens. A 72-year-old woman was admitted to Kangwon National University Hospital for empyema. The patient had no history of trauma, a dental procedure, or aspiration, and was treated using empirical antibiotics and by drainage of pleural fluid. Bacteria species that cause empyema are usually not detected, but on the 4th day of admission, C. perfringens was isolated from the pleural space. The patient was continuously treated with antibiotics for C. perfringens and drainage, and was discharged 25 days after admission with almost a fully recovered status. Increased awareness of Clostrium species infection in the elderly is needed to ensure appropriate treatment.

The Influence of Asian Dust, Haze, Mist, and Fog on Hospital Visits for Airway Diseases / 결핵및호흡기질환

BACKGROUND: Asian dust is known to have harmful effects on the respiratory system. Respiratory conditions are also influenced by environmental conditions regardless of the presence of pollutants. The same pollutant can have different effects on the airway when the air is dry compared with when it is humid. We investigated hospital visits for chronic obstructive pulmonary disease (COPD) and asthma in relation to the environmental conditions. METHODS: We conducted a retrospective study using the Korean National Health Insurance Service claims database of patients who visited hospitals in Chuncheon between January 2006 and April 2012. Asian dust, haze, mist, and fog days were determined using reports from the Korea Meteorological Administration. Hospital visits for asthma or COPD on the index days were compared with the comparison days. We used two-way case-crossover techniques with one to two matching. RESULTS: The mean hospital visits for asthma and COPD were 59.37 +/- 34.01 and 10.04 +/- 6.18 per day, respectively. Hospital visits for asthma significantly increased at lag0 and lag1 for Asian dust (relative risk [RR], 1.10; 95% confidence interval [CI], 1.01-1.19; p<0.05) and haze (RR, 1.13; 95% CI, 1.06-1.22; p<0.05), but were significantly lower on misty (RR, 0.89; 95% CI, 0.80-0.99; p<0.05) and foggy (RR, 0.89; 95% CI, 0.84-0.93; p<0.05) days than on control days. The hospital visits for COPD also significantly increased on days with Asian dust (RR, 1.29; 95% CI, 1.05-1.59; p<0.05), and were significantly lower at lag4 for foggy days, compared with days without fog (RR, 0.85; 95% CI, 0.75-0.97; p<0.05). CONCLUSION: Asian dust showed an association with airway diseases and had effects for several days after the exposure. In contrast to Asian dust, mist and fog, which occur in humid air conditions, showed the opposite effects on airway diseases, after adjusting to the pollutants. It would require more research to investigate the effects of various air conditions on airway diseases.

A Case of Interventional Lung Assist Application in a Patient with Pulmonary Arteriovenous Malformation Complicating Massive Hemoptysis / 계명의대학술지

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.

Influence of Environmental Exposures on Patients with Chronic Obstructive Pulmonary Disease in Korea / 결핵및호흡기질환

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. METHODS: The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. RESULTS: Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. CONCLUSION: COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

Study Design and Outcomes of Korean Obstructive Lung Disease (KOLD) Cohort Study / 결핵및호흡기질환

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.