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Dr. Hsiao-Yu Yang
Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan, No. 17 Xuzhou Road, Taipei 100, Taiwan

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Research Keywords & Expertise

0 noise-induced hearing loss
0 Occupation and environmental lung diseases
0 Health risk of non-asbestiform asbestos
0 Earlier diagnosis of asbestos-related diseases using GC/MS and sensor-array technology
0 Cancer risk for talc exposure

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Aristolochic acids
noise-induced hearing loss
Occupational kidney disease and urological cancer among Chinese herbalists exposed to herbs containing aristolochic acid

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Journal article
Published: 30 June 2021 in Scientific Reports
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For malignant pleural effusions, pleural fluid cytology is a diagnostic method, but sensitivity is low. The pleural fluid contains metabolites directly released from cancer cells. The objective of this study was to diagnose lung cancer with malignant pleural effusion using the volatilomic profiling method. We recruited lung cancer patients with malignant pleural effusion and patients with nonmalignant diseases with pleural effusion as controls. We analyzed the headspace air of the pleural effusion by gas chromatography-mass spectrometry. We used partial least squares discriminant analysis (PLS-DA) to identify metabolites and the support vector machine (SVM) to establish the prediction model. We split data into a training set (80%) and a testing set (20%) to validate the accuracy. A total of 68 subjects were included in the final analysis. The PLS-DA showed high discrimination with an R2 of 0.95 and Q2 of 0.58. The accuracy of the SVM in the test set was 0.93 (95% CI 0.66, 0.998), the sensitivity was 83%, the specificity was 100%, and kappa was 0.85, and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.86, 1.00). Volatile metabolites of pleural effusion might be used in patients with cytology-negative pleural effusion to rule out malignancy.

ACS Style

Ke-Cheng Chen; Shih-Wei Tsai; Xiang Zhang; Chian Zeng; Hsiao-Yu Yang. The investigation of the volatile metabolites of lung cancer from the microenvironment of malignant pleural effusion. Scientific Reports 2021, 11, 1 -10.

AMA Style

Ke-Cheng Chen, Shih-Wei Tsai, Xiang Zhang, Chian Zeng, Hsiao-Yu Yang. The investigation of the volatile metabolites of lung cancer from the microenvironment of malignant pleural effusion. Scientific Reports. 2021; 11 (1):1-10.

Chicago/Turabian Style

Ke-Cheng Chen; Shih-Wei Tsai; Xiang Zhang; Chian Zeng; Hsiao-Yu Yang. 2021. "The investigation of the volatile metabolites of lung cancer from the microenvironment of malignant pleural effusion." Scientific Reports 11, no. 1: 1-10.

Workplace
Published: 09 June 2021 in Occupational and Environmental Medicine
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Objectives Chronic kidney disease of undetermined or non-traditional aetiology (CKDu or CKDnT) has been reported in Mesoamerica among farmers under heat stress. Epidemiological evidence was lacking in Asian countries with similar climatic conditions. The objective of this study was to investigate the prevalence of CKDu and possible risk factors. Methods We used the data from the Changhua Community-based Integrated Screening programme from 2005 to 2014, which is the annual screening for chronic diseases in Taiwan’s largest rice-farming county since 2005. Our study population included farmers and non-farmers aged 15–60 years. CKDu was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 at age under 60 years without hypertension, diabetes, proteinuria, haematuria or using Chinese herbal medicine. We estimated the adjusted prevalence OR (POR) of CKDu by farmers, age, sex, education, urbanisation, smoking, body mass index, hyperuricaemia, hyperlipidaemia, heart disease and chronic liver disease. Results 5555 farmers and 35 761 non-farmers were included in this study. CKDu accounted for 48.9% of all CKD cases. The prevalence of CKDu was 2.3% in the farmers and 0.9% in the non-farmers. The crude POR of CKDu in farmers compared with non-farmers was 2.73 (2.13–3.50), and the adjusted POR was 1.45 (1.10–1.90). Dehydration (blood urea nitrogen-to-creatinine ratio >20) was found in 22% of the farmers and 14% of the non-farmers. Conclusions Farmers in subtropical Asian countries are at increased risk of CKDu. Governments should take the CKDu epidemics seriously and provide farmers with occupational health education programmes on thermal hazards.

ACS Style

Jerry Che-Jui Chang; Hsiao-Yu Yang. Epidemiology of chronic kidney disease of undetermined aetiology in Taiwanese farmers: a cross-sectional study from Changhua Community-based Integrated Screening programme. Occupational and Environmental Medicine 2021, 1 .

AMA Style

Jerry Che-Jui Chang, Hsiao-Yu Yang. Epidemiology of chronic kidney disease of undetermined aetiology in Taiwanese farmers: a cross-sectional study from Changhua Community-based Integrated Screening programme. Occupational and Environmental Medicine. 2021; ():1.

Chicago/Turabian Style

Jerry Che-Jui Chang; Hsiao-Yu Yang. 2021. "Epidemiology of chronic kidney disease of undetermined aetiology in Taiwanese farmers: a cross-sectional study from Changhua Community-based Integrated Screening programme." Occupational and Environmental Medicine , no. : 1.

Journal article
Published: 12 April 2021 in International Journal of Environmental Research and Public Health
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The current understanding of ambient temperature and its link to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The objective of this study was to explore the environmental and climatic risk factors for SARS-CoV-2. For this study, we analyzed the data at the beginning of the outbreak (from 20 January to 31 March 2020) to avoid the influence of preventive or control measures. We obtained the number of cases and deaths due to SARS-CoV-2, international tourism, population age, universal health coverage, regional factors, the SARS-CoV-2 testing rate, and population density of a country. A total of 154 countries were included in this study. There were high incidence rates and mortality risks in the countries that had an average ambient temperature between 0 and 10 °C. The adjusted incidence rate for temperatures between 0 and 10 °C was 2.91 (95% CI 2.87–2.95). We randomly divided the data into a training set (80% of data) for model derivation and a test set (20% of data) for validation. Using a random forest statistical model, the model had high accuracy for predicting the high epidemic status of a country (ROC = 95.5%, 95% CI 87.9–100.0%) in the test set. Population age, temperature, and international tourism were the most important factors affecting the risk of SARS-CoV-2 in a country. An understanding the determinants of the SARS-CoV-2 outbreak can help to design better strategies for disease control. This study highlights the need to consider thermal effect in the prevention of emerging infectious diseases.

ACS Style

Hsiao-Yu Yang; Jason Lee. The Impact of Temperature on the Risk of COVID-19: A Multinational Study. International Journal of Environmental Research and Public Health 2021, 18, 4052 .

AMA Style

Hsiao-Yu Yang, Jason Lee. The Impact of Temperature on the Risk of COVID-19: A Multinational Study. International Journal of Environmental Research and Public Health. 2021; 18 (8):4052.

Chicago/Turabian Style

Hsiao-Yu Yang; Jason Lee. 2021. "The Impact of Temperature on the Risk of COVID-19: A Multinational Study." International Journal of Environmental Research and Public Health 18, no. 8: 4052.

Journal article
Published: 16 February 2021 in BMJ Open
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Objectives The objective of this study was to explore the impact of Taiwan’s Family Practice Integrated Care Project (FPICP) on hospitalisation. Design A population-based cohort study compared the hospitalisation rates for ambulatory care sensitive conditions (ACSCs) among FPICP participating and non-participating patients during 2011–2015. Setting The study accessed the FPICP reimbursement database of Taiwan’s National Health Insurance (NHI) administration containing all NHI administration-selected patients for FPICP enrolment. Participants The NHI administration-selected candidates from 2011 to 2015 became FPICP participants if their primary care physicians joined the project, otherwise they became non-participants. Interventions The intervention of interest was enrolment in the FPICP or not. The follow-up time interval for calculating the rate of hospitalisation was the year in which the patient was selected for FPICP enrolment or not. Primary outcome measures The study’s primary outcome measures were hospitalisation rates for ACSC, including asthma/chronic obstructive pulmonary disease (COPD), diabetes or its complications and heart failure. Logistic regression was used to calculate the ORs concerning the influence of FPICP participation on the rate of hospitalisation for ACSC. Results The enrolled population for data analysis was between 3.94 and 5.34 million from 2011 to 2015. Compared to non-participants, FPICP participants had lower hospitalisation for COPD/asthma (28.6‰–35.9‰ vs 37.9‰–42.3‰) and for diabetes or its complications (10.8‰–14.9‰ vs 12.7‰–18.1‰) but not for congestive heart failure. After adjusting for age, sex and level of comorbidities by logistic regression, participation in the FPICP was associated with lower hospitalisation for COPD/asthma (OR 0.91, 95% CI 0.87 to 0.94 in 2015) and for diabetes or its complications (OR 0.87, 95% CI 0.83 to 0.92 in 2015). Conclusion Participation in the FPICP is an independent protective factor for preventable ACSC hospitalisation. Team-based community healthcare programs such as the FPICP can strengthen primary healthcare capacity.

ACS Style

Chyi-Feng Jeff Jan; Che-Jui Jerry Chang; Shinn-Jang Hwang; Tzeng-Ji Chen; Hsiao-Yu Yang; Yu-Chun Chen; Cheng-Kuo Huang; Tai-Yuan Chiu. Impact of team-based community healthcare on preventable hospitalisation: a population-based cohort study in Taiwan. BMJ Open 2021, 11, e039986 .

AMA Style

Chyi-Feng Jeff Jan, Che-Jui Jerry Chang, Shinn-Jang Hwang, Tzeng-Ji Chen, Hsiao-Yu Yang, Yu-Chun Chen, Cheng-Kuo Huang, Tai-Yuan Chiu. Impact of team-based community healthcare on preventable hospitalisation: a population-based cohort study in Taiwan. BMJ Open. 2021; 11 (2):e039986.

Chicago/Turabian Style

Chyi-Feng Jeff Jan; Che-Jui Jerry Chang; Shinn-Jang Hwang; Tzeng-Ji Chen; Hsiao-Yu Yang; Yu-Chun Chen; Cheng-Kuo Huang; Tai-Yuan Chiu. 2021. "Impact of team-based community healthcare on preventable hospitalisation: a population-based cohort study in Taiwan." BMJ Open 11, no. 2: e039986.

Preprint content
Published: 18 January 2021
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Lung cancer is the leading cause of cancer death. For malignant pleural effusions, pleural fluid cytology is a diagnostic method, but sensitivity is low. Many patients need to undergo invasive diagnostic tests such as thoracoscopic pleural biopsy. Pleural space is an enclosed microenvironment, and the pleural fluid contains metabolites directly released from cancer cells. The objective of this study was to diagnose lung cancer with malignant pleural effusion using the volatilomic profiling method. We recruited lung cancer patients with malignant pleural effusion and patients with nonmalignant diseases with pleural effusion as controls. We analyzed the headspace air of the pleural effusion by gas chromatography-mass spectrometry. We used partial least squares discriminant analysis (PLS-DA) to identify metabolites and the support vector machine (SVM) to establish the prediction model. We split data into a training set (80%) and a testing set (20%) to validate the accuracy. A total of 68 subjects were included in the final analysis. The PLS-DA showed high discrimination with an R2 of 0.95 and Q2 of 0.58. The accuracy of the SVM in the test set was 0.93 (95% CI: 0.66, 0.998), and kappa was 0.85, and the area under the receiver operating characteristic curve was 0.96 (95% CI: 0.86, 1.00). Pathway analysis revealed disturbances in pyruvate metabolism, the tricarboxylic acid, glycolysis, and lysine degradation. The volatile metabolites identified from malignant pleural effusion of lung cancer were primarily methylated alkanes. The pleural effusion contained volatile metabolites that have high accuracy in diagnosing lung cancer with malignant pleural effusion.

ACS Style

Ke-Cheng Chen; Shih-Wei Tsai; Xiang Zhang; Chian Zeng; Hsiao-Yu Yang. The Investigation of the Volatile Metabolites of Lung Cancer From the Microenvironment of Malignant Pleural Effusion. 2021, 1 .

AMA Style

Ke-Cheng Chen, Shih-Wei Tsai, Xiang Zhang, Chian Zeng, Hsiao-Yu Yang. The Investigation of the Volatile Metabolites of Lung Cancer From the Microenvironment of Malignant Pleural Effusion. . 2021; ():1.

Chicago/Turabian Style

Ke-Cheng Chen; Shih-Wei Tsai; Xiang Zhang; Chian Zeng; Hsiao-Yu Yang. 2021. "The Investigation of the Volatile Metabolites of Lung Cancer From the Microenvironment of Malignant Pleural Effusion." , no. : 1.

Journal article
Published: 24 September 2020 in Scientific Reports
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Quartz can increase oxidative stress, lipid peroxidation, and inflammation. The objective of this study was to explore the volatile biomarkers of quartz-induced lung injury using a lung alveolar cell model. We exposed the human alveolar A549 cell line to 0, 200, and 500 μg/mL quartz particles for 24 h and used gas chromatography–mass spectrometry to measure the volatile metabolites in the headspace air of cells. We identified ten volatile metabolites that had concentration–response relationships with particles exposure, including 1,2,4-oxadiazole, 5-(4-nitrophenyl)-3-phenyl- (CAS: 28825-12-9), 2,6-dimethyl-6-trifluoroacetoxyoctane (CAS: 61986-67-2), 3-buten-1-amine, N,N-dimethyl- (CAS: 55831-89-5), 2-propanol, 2-methyl- (CAS: 75-65-0), glycolaldehyde dimethyl acetal (CAS: 30934-97-5), propanoic acid, 2-oxo-, ethyl ester (CAS: 617-35-6), octane (CAS: 111-65-9), octane, 3,3-dimethyl- (CAS: 4110-44-5), heptane, 2,3-dimethyl- (CAS: 3074-71-3) and ethanedioic acid, bis(trimethylsilyl) ester (CAS: 18294-04-7). The volatile biomarkers are generated through the pathways of propanoate and nitrogen metabolism. The volatile biomarkers of the alkanes and methylated alkanes are related to oxidative and lipid peroxidation of the cell membrane. The lung alveolar cell model has the potential to explore the volatile biomarkers of particulate-induced lung injury.

ACS Style

Hsiao-Chi Chuang; Shih-Wei Tsai; Ruei-Hao Shie; Yi-Chia Lu; Sheng-Rong Song; Sheng-Hsiu Huang; Hsin-Yi Peng; Hsiao-Yu Yang. A novel lung alveolar cell model for exploring volatile biomarkers of particle-induced lung injury. Scientific Reports 2020, 10, 1 -10.

AMA Style

Hsiao-Chi Chuang, Shih-Wei Tsai, Ruei-Hao Shie, Yi-Chia Lu, Sheng-Rong Song, Sheng-Hsiu Huang, Hsin-Yi Peng, Hsiao-Yu Yang. A novel lung alveolar cell model for exploring volatile biomarkers of particle-induced lung injury. Scientific Reports. 2020; 10 (1):1-10.

Chicago/Turabian Style

Hsiao-Chi Chuang; Shih-Wei Tsai; Ruei-Hao Shie; Yi-Chia Lu; Sheng-Rong Song; Sheng-Hsiu Huang; Hsin-Yi Peng; Hsiao-Yu Yang. 2020. "A novel lung alveolar cell model for exploring volatile biomarkers of particle-induced lung injury." Scientific Reports 10, no. 1: 1-10.

Journal article
Published: 07 February 2020 in Respiratory Research
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Background Ventilator-associated pneumonia (VAP) is a significant cause of mortality in the intensive care unit. Early diagnosis of VAP is important to provide appropriate treatment and reduce mortality. Developing a noninvasive and highly accurate diagnostic method is important. The invention of electronic sensors has been applied to analyze the volatile organic compounds in breath to detect VAP using a machine learning technique. However, the process of building an algorithm is usually unclear and prevents physicians from applying the artificial intelligence technique in clinical practice. Clear processes of model building and assessing accuracy are warranted. The objective of this study was to develop a breath test for VAP with a standardized protocol for a machine learning technique. Methods We conducted a case-control study. This study enrolled subjects in an intensive care unit of a hospital in southern Taiwan from February 2017 to June 2019. We recruited patients with VAP as the case group and ventilated patients without pneumonia as the control group. We collected exhaled breath and analyzed the electric resistance changes of 32 sensor arrays of an electronic nose. We split the data into a set for training algorithms and a set for testing. We applied eight machine learning algorithms to build prediction models, improving model performance and providing an estimated diagnostic accuracy. Results A total of 33 cases and 26 controls were used in the final analysis. Using eight machine learning algorithms, the mean accuracy in the testing set was 0.81 ± 0.04, the sensitivity was 0.79 ± 0.08, the specificity was 0.83 ± 0.00, the positive predictive value was 0.85 ± 0.02, the negative predictive value was 0.77 ± 0.06, and the area under the receiver operator characteristic curves was 0.85 ± 0.04. The mean kappa value in the testing set was 0.62 ± 0.08, which suggested good agreement. Conclusions There was good accuracy in detecting VAP by sensor array and machine learning techniques. Artificial intelligence has the potential to assist the physician in making a clinical diagnosis. Clear protocols for data processing and the modeling procedure needed to increase generalizability.

ACS Style

Chung-Yu Chen; Wei-Chi Lin; Hsiao-Yu Yang. Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research. Respiratory Research 2020, 21, 45 -12.

AMA Style

Chung-Yu Chen, Wei-Chi Lin, Hsiao-Yu Yang. Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research. Respiratory Research. 2020; 21 (1):45-12.

Chicago/Turabian Style

Chung-Yu Chen; Wei-Chi Lin; Hsiao-Yu Yang. 2020. "Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research." Respiratory Research 21, no. 1: 45-12.

Research article
Published: 04 April 2019 in PLOS ONE
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Workers processing nephrite, antigorite, or talc may be exposed to paragenetic asbestos minerals. An effective screening method for pneumoconiosis in workers exposed to asbestos-contaminated minerals is still lacking. The objective of this study was to assess the diagnostic accuracy of serum and urinary biomarkers for pneumoconiosis in workers exposed to asbestos-contaminated minerals. We conducted a case-control study in a cohort of stone craft workers in Hualien, where asbestos, nephrite, antigorite, and talc are produced. A total of 140 subjects were screened between March 2013 and July 2014. All subjects received a questionnaire survey and a health examination that included a physical examination; chest X-ray; and tests for standard pulmonary function, fractional exhaled nitric oxide, serum soluble mesothelin-related peptide (SMRP), fibulin-3, carcinoembryonic antigen (CEA), and urinary 8-Oxo-2'-deoxyguanosine (8-OHdG)/creatinine. After excluding subjects with uraemia and chronic obstructive pulmonary disease (COPD), we included 48 subjects with pneumoconiosis and 90 control subjects without pneumoconiosis for analysis. In terms of occupational history, 43/48 (90%) case subjects and 68% (61/90) of the control subjects had processed asbestos-contaminated minerals, including nephrite, antigorite, and talc. The case group had decreased pulmonary function in forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow between 25% and 75% of the FVC. The levels of SMRP, fibulin-3, urinary 8-OHdG/creatinine, and CEA were higher in the case group than in the control group. Subjects exposed to nephrite had significantly higher SMRP levels (0.84 ± 0.52 nM) than subjects exposed to other types of minerals (0.60 ± 0.30 nM). A dose-response relationship was observed between the SMRP level and the severity of pneumoconiosis. Machine learning algorithms, including variables of sex, age, SMRP, fibulin-3, CEA, and 8-OHdG/creatinine, can predict pneumoconiosis with high accuracy. The areas under the receiver operating characteristic curves ranged from 0.7 to 1.0. We suggest that SMRP and fibulin-3 could be used as biomarkers of pneumoconiosis in workers exposed to asbestos-contaminated minerals.

ACS Style

Hsiao-Yu Yang. Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals. PLOS ONE 2019, 14, e0214808 .

AMA Style

Hsiao-Yu Yang. Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals. PLOS ONE. 2019; 14 (4):e0214808.

Chicago/Turabian Style

Hsiao-Yu Yang. 2019. "Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals." PLOS ONE 14, no. 4: e0214808.

Journal article
Published: 28 February 2019 in International Journal of Environmental Research and Public Health
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The present investigation was designed to explore the risk of stomach cancer by oral intake of talc powder without asbestos. We conducted a population-based cohort study on a randomly sampled cohort from Taiwan's health insurance database, with population of 1,000,000. The study participants were followed up through 2013. The outcome event of interest was the diagnosis of stomach cancer. The exposure of interest was the prescription of talc powder. Cox regression analyses were performed respectively. There were 584,077 persons without talc exposure and 21,575 talc users, 1849 diagnosed with stomach cancer. Persons with exposure of talc had a higher hazard ratio of stomach cancer (adjusted hazard ratio, 2.13; 95% confidence interval (CI), 1.54⁻2.94; p < 0.001). Classification by cumulative exposure of talc yielded adjusted hazard ratios of stomach cancer of 1.58 (95% CI, 0.79⁻3.17; p = 0.19) and 2.30 (95% CI, 1.48⁻3.57; p < 0.001) among persons with high (>21 g) and medium (6⁻21 g) exposure of talc, as compared to the low-exposure counterparts. Our data demonstrated positive association between increased risk of stomach cancer and oral intake of talc without asbestos. Despite the absence of dose-response effect, there might be a link between stomach cancer and talc.

ACS Style

Che-Jui Chang; Yao-Hsu Yang; Pau-Chung Chen; Hsin-Yi Peng; Yi-Chia Lu; Sheng-Rong Song; Hsiao-Yu Yang. Stomach Cancer and Exposure to Talc Powder without Asbestos via Chinese Herbal Medicine: A Population-Based Cohort Study. International Journal of Environmental Research and Public Health 2019, 16, 717 .

AMA Style

Che-Jui Chang, Yao-Hsu Yang, Pau-Chung Chen, Hsin-Yi Peng, Yi-Chia Lu, Sheng-Rong Song, Hsiao-Yu Yang. Stomach Cancer and Exposure to Talc Powder without Asbestos via Chinese Herbal Medicine: A Population-Based Cohort Study. International Journal of Environmental Research and Public Health. 2019; 16 (5):717.

Chicago/Turabian Style

Che-Jui Chang; Yao-Hsu Yang; Pau-Chung Chen; Hsin-Yi Peng; Yi-Chia Lu; Sheng-Rong Song; Hsiao-Yu Yang. 2019. "Stomach Cancer and Exposure to Talc Powder without Asbestos via Chinese Herbal Medicine: A Population-Based Cohort Study." International Journal of Environmental Research and Public Health 16, no. 5: 717.

Dataset
Published: 17 February 2019 in protocols.io
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ACS Style

Hsiao-Yu Yang. Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals v1. protocols.io 2019, 1 .

AMA Style

Hsiao-Yu Yang. Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals v1. protocols.io. 2019; ():1.

Chicago/Turabian Style

Hsiao-Yu Yang. 2019. "Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals v1." protocols.io , no. : 1.

Clinical trial
Published: 28 August 2018 in Sensors
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Lung cancer is the leading cause of cancer death around the world, and lung cancer screening remains challenging. This study aimed to develop a breath test for the detection of lung cancer using a chemical sensor array and a machine learning technique. We conducted a prospective study to enroll lung cancer cases and non-tumour controls between 2016 and 2018 and analysed alveolar air samples using carbon nanotube sensor arrays. A total of 117 cases and 199 controls were enrolled in the study of which 72 subjects were excluded due to having cancer at another site, benign lung tumours, metastatic lung cancer, carcinoma in situ, minimally invasive adenocarcinoma, received chemotherapy or other diseases. Subjects enrolled in 2016 and 2017 were used for the model derivation and internal validation. The model was externally validated in subjects recruited in 2018. The diagnostic accuracy was assessed using the pathological reports as the reference standard. In the external validation, the areas under the receiver operating characteristic curve (AUCs) were 0.91 (95% CI = 0.79–1.00) by linear discriminant analysis and 0.90 (95% CI = 0.80–0.99) by the supportive vector machine technique. The combination of the sensor array technique and machine learning can detect lung cancer with high accuracy.

ACS Style

Chi-Hsiang Huang; Chian Zeng; Yi-Chia Wang; Hsin-Yi Peng; Chia-Sheng Lin; Che-Jui Chang; Hsiao-Yu Yang. A Study of Diagnostic Accuracy Using a Chemical Sensor Array and a Machine Learning Technique to Detect Lung Cancer. Sensors 2018, 18, 2845 .

AMA Style

Chi-Hsiang Huang, Chian Zeng, Yi-Chia Wang, Hsin-Yi Peng, Chia-Sheng Lin, Che-Jui Chang, Hsiao-Yu Yang. A Study of Diagnostic Accuracy Using a Chemical Sensor Array and a Machine Learning Technique to Detect Lung Cancer. Sensors. 2018; 18 (9):2845.

Chicago/Turabian Style

Chi-Hsiang Huang; Chian Zeng; Yi-Chia Wang; Hsin-Yi Peng; Chia-Sheng Lin; Che-Jui Chang; Hsiao-Yu Yang. 2018. "A Study of Diagnostic Accuracy Using a Chemical Sensor Array and a Machine Learning Technique to Detect Lung Cancer." Sensors 18, no. 9: 2845.

Review
Published: 09 August 2018 in Journal of the Formosan Medical Association
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Talc powder is widely used in various industries, but the carcinogenic effects associated with talc are not well understood. The objective of this study was to estimate the risk of stomach cancer after occupational talc exposure. We conducted a meta-analysis was performed to calculate the meta-relative risk (mRR) of stomach cancer. We searched the MEDLINE, EMBASE, CNKI and Wanfang Data databases for publications prior to January 1, 2017 using talc, cancer, and mortality as the search terms. Only cohort studies with occupational talc exposure and stomach cancer statistics were included. All pooled analyses were based on random-effects models. We selected 13 observational studies (12 publications) for the meta-analysis, and heterogeneity was observed among studies. Workers exposed to all forms of talc had a significantly increased mRR of 1.21 (95% CI: 1.03–1.42, p = 0.02) for stomach cancer. Workers exposed to talc not containing asbestiform fibers also had an increased mRR of 1.26 (95% CI: 0.97–1.63, p = 0.09). The available data showed a positive association between occupational talc exposure and risk of stomach cancer. The association between talc not containing asbestiform fibers and risk of stomach cancer was not significant. Further epidemiological studies are required to evaluate the safety of talc.

ACS Style

Che-Jui Chang; Yu-Kang Tu; Pau-Chung Chen; Hsiao-Yu Yang. Talc exposure and risk of stomach cancer: Systematic review and meta-analysis of occupational cohort studies. Journal of the Formosan Medical Association 2018, 119, 781 -792.

AMA Style

Che-Jui Chang, Yu-Kang Tu, Pau-Chung Chen, Hsiao-Yu Yang. Talc exposure and risk of stomach cancer: Systematic review and meta-analysis of occupational cohort studies. Journal of the Formosan Medical Association. 2018; 119 (4):781-792.

Chicago/Turabian Style

Che-Jui Chang; Yu-Kang Tu; Pau-Chung Chen; Hsiao-Yu Yang. 2018. "Talc exposure and risk of stomach cancer: Systematic review and meta-analysis of occupational cohort studies." Journal of the Formosan Medical Association 119, no. 4: 781-792.

Research article
Published: 07 May 2018 in International Journal of Cancer
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It was suspected that aristolochic acid‐induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV‐infected patients. We conducted a retrospective, population‐based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV‐infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow‐up period of 11,643,790 person‐years and the overall incidence rate was 291.8 HCCs per 100,000 person‐years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11 to 1.16), 1.21 (95% CI, 1.13 to 1.29), 1.37 (95% CI, 1.24 to 1.50), and 1.61 (95% CI, 1.40 to 1.84) for estimated aristolochic acid of 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose‐response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection; suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC. This article is protected by copyright. All rights reserved.

ACS Style

Chi‐Jen Chen; Yao‐Hsu Yang; Meng-Hung Lin; Chuan‐Pin Lee; Yu‐Tse Tsan; Ming‐Nan Lai; Hsiao‐Yu Yang; Wen‐Chao Ho; Pau‐Chung Chen; and the Health Data Analysis in Taiwan (hDATa) Research Group. Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. International Journal of Cancer 2018, 143, 1578 -1587.

AMA Style

Chi‐Jen Chen, Yao‐Hsu Yang, Meng-Hung Lin, Chuan‐Pin Lee, Yu‐Tse Tsan, Ming‐Nan Lai, Hsiao‐Yu Yang, Wen‐Chao Ho, Pau‐Chung Chen, and the Health Data Analysis in Taiwan (hDATa) Research Group. Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. International Journal of Cancer. 2018; 143 (7):1578-1587.

Chicago/Turabian Style

Chi‐Jen Chen; Yao‐Hsu Yang; Meng-Hung Lin; Chuan‐Pin Lee; Yu‐Tse Tsan; Ming‐Nan Lai; Hsiao‐Yu Yang; Wen‐Chao Ho; Pau‐Chung Chen; and the Health Data Analysis in Taiwan (hDATa) Research Group. 2018. "Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection." International Journal of Cancer 143, no. 7: 1578-1587.

Conference paper
Published: 24 April 2018 in Epidemiology
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Introduction Lung cancer is the leading cause of cancer death in the world. The challenge of screening for early stage lung cancer is still unresolved. The exploration of metabolites in breathe using sensor array technique may become a powerful screening tool to solve the problem. Methods We conducted a prospective study to enrol cases of lung cancer and controls who received surgery for gall bladder stone, hernia, hemorrhoid resection, and thoracoscopic surgery in the same hospital between July 2016 and June 2017. The alveolar air of subjects were collected under the guidance of mainstream carbon dioxide analyzer. An electronic nose composed of 32 carbon nanotubes sensors was used to measure the VOCs of the alveolar air. The diagnostic accuracy was analysed by linear discriminant analysis (LDA) using the pathological reports as the reference standard. Results After excluding 2 subjects with technical problems in sampling, 12 subjects with cancers in other sites, benign lung tumour, or metastatic lung cancer, 5 subjects received chemotherapy, 5 subjects with diabetes, 2 subjects with asthma, and 2 subjects with chronic obstructive pulmonary disease, a total of 17 cases and 105 controls were used in the final analysis. We randomly split the data into 80% for model building (training set) and 20% for validation (test set). By LDA, the accuracy, sensitivity, specificity, false positive rate, false negative rate, and ROC-AUC were 96.9%, 75.0%, 100.0%, 0%, 25%, and 0.98 (95% CI: 0.96 to 1.00) in the training set, and 84.0%, 80.0%, 85.0%, 15.0%, 20.0% and 0.84 (95% CI: 0.62 to 1.00) in the test set. Conclusion The use of sensor array technique to explore the metabolites in breathe may become a powerful tool in the screening for lung cancer. Standardised procedures to eliminate confounding factors are warranted before clinical application.

ACS Style

Chi-Hsiang Huang; Chian Zeng; Che-Jui Chang; Hsin-Yi Peng; Yi-Chia Wang; Hsiao-Yu Yang. 1206 Application of metabolomic science in the detection of lung cancer: a case-control study. Epidemiology 2018, 75, A122 -A122.

AMA Style

Chi-Hsiang Huang, Chian Zeng, Che-Jui Chang, Hsin-Yi Peng, Yi-Chia Wang, Hsiao-Yu Yang. 1206 Application of metabolomic science in the detection of lung cancer: a case-control study. Epidemiology. 2018; 75 ():A122-A122.

Chicago/Turabian Style

Chi-Hsiang Huang; Chian Zeng; Che-Jui Chang; Hsin-Yi Peng; Yi-Chia Wang; Hsiao-Yu Yang. 2018. "1206 Application of metabolomic science in the detection of lung cancer: a case-control study." Epidemiology 75, no. : A122-A122.

Conference paper
Published: 24 April 2018 in Respiratory Disorders
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Introduction Pneumoconiosis resurged in recent years but current medical surveillance programs have flaws that result in low detection rate. Development of new screening tools is warranted. The objective of the study was to develop serum and urinary screening tests for pneumoconiosis. Methods We conducted a cross-sectional study in 140 stone workers between March 2013 and July 2014. We compared serum soluble mesothelin-related peptide (SMRP), fibulin-3, and urinary 8-Oxo-2’-deoxyguanosine (8-OHdG)/Creatinine between cases of pneumoconiosis and control. Using the ILO international classification of radiographs of pneumoconiosis profusion subcategory &x2267;1/0 combined with restrictive type ventilatory impairment in standard pulmonary function test (FVC 70% of predicted) as the reference standard, we calculated sensitivity, specificity, false positive, false negative, and the likelihood ratio of the biomarkers. We created the receiver operating characteristic (ROC), calculated the area under the curve (AUC) and decided the cut-off values using the Youden index. Results After excluding one subject with uremia and one subject with COPD, a total of 138 subjects were enrolled that included 20 cases and 118 controls. The ROC-AUC was 0.7 for SMRP (95% CI: 0.5 to 0.8), 0.5 for Fibulin-3 (95% CI: 0.4 to 0.7), and 0.5 for 8-OHdG/Creatinine (95% CI: 0.4 to 0.6). There was a dose-response relationship between SMRP and the severity of pneumoconiosis. Using SMRP larger than 0.62 nM as the cutoff value, the diagnostic test had the highest positive likelihood ratio followed by using fibulin-3 larger than 43.9 ng/mL as cutoff value, and then101.65 ng/mg for 8-OHdG/Creatinine. In the case group, 65% of subjects processed asbestos-contaminated ores including nephrite, antigorite, or talc. Subjects exposed to nephrite had significantly higher level of SMRP than exposed to other types of stones. Conclusion SMRP might be used in the screening for workers exposed to asbestos contaminated minerals.

ACS Style

Hsiao-Yu Yang; Pau-Chung Chen. 674 Assessment of serum and urinary biomarkers for pneumoconiosis in a cohort of stone workers exposed to asbestos contaminated minerals. Respiratory Disorders 2018, 75, A457 -A457.

AMA Style

Hsiao-Yu Yang, Pau-Chung Chen. 674 Assessment of serum and urinary biomarkers for pneumoconiosis in a cohort of stone workers exposed to asbestos contaminated minerals. Respiratory Disorders. 2018; 75 ():A457-A457.

Chicago/Turabian Style

Hsiao-Yu Yang; Pau-Chung Chen. 2018. "674 Assessment of serum and urinary biomarkers for pneumoconiosis in a cohort of stone workers exposed to asbestos contaminated minerals." Respiratory Disorders 75, no. : A457-A457.

Conference paper
Published: 24 April 2018 in Respiratory Disorders
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Introduction Current medical surveillance program has flaw that may result in poor detection of early pneumoconiosis around the world. Breath analyses have attracted substantial attention in the screening of occupational environmental lung disease. Pneumoconiosis could generate specific volatile organic compounds (VOCs) that may constitute a specific breath print for diagnosis. The objective of this study was to develop a breath test for pneumoconiosis by analysing VOCs using senor array technique. Methods We conducted a case-control study and enrolled study subjects from stone workers in Hualien between October 2016 and November 2016. One litter of breath air was collected after five minutes of tidal breathing through a non-rebreathing valve with inspiratory VOC-filter, and storage by a Tedlar bag. The air was analysed by a 32 nanocomposite sensor array electronic nose within 30 min. Using the ILO/ICRP profusion category ≥1/1 in chest X-ray as the reference standard, we assessed the diagnostic accuracy of the breath test. Data were randomly split into 80% for model building and 20% for validation. Result After excluding three subjects with poorly controlled diabetes mellitus with fasting serum glucose level >200 mg/dl and one subjects of asthma under medication, a total of 98 subjected were used in final analysis that included 34 cases of pneumoconiosis and 64 healthy controls. By linear discriminant analysis, the sensitivity was 88.0%, specificity was 67.9%, accuracy was 80.8%, and ROC-AUC was 0.91 (95% CI: 0.85 to 0.97) in the training set. In the validation set, the sensitivity was 66.7%, specificity was 71.4%, accuracy was 70.0%, and ROC-AUC was 0.86 (95% CI: 0.69 to 1.00). Discussion Breath test may have potential in screening for pneumoconiosis. A multi-centre study is warranted to establish a reliable model and the procedures must be standardised to prevent confounding factors before clinical application.

ACS Style

Hsin-Yi Peng; Che-Jui Chang; Pau-Chung Chen; Hsiao-Yu Yang. 690 Breath test for pneumoconiosis using an electronic nose: a case-control study. Respiratory Disorders 2018, 75, A459 -A460.

AMA Style

Hsin-Yi Peng, Che-Jui Chang, Pau-Chung Chen, Hsiao-Yu Yang. 690 Breath test for pneumoconiosis using an electronic nose: a case-control study. Respiratory Disorders. 2018; 75 ():A459-A460.

Chicago/Turabian Style

Hsin-Yi Peng; Che-Jui Chang; Pau-Chung Chen; Hsiao-Yu Yang. 2018. "690 Breath test for pneumoconiosis using an electronic nose: a case-control study." Respiratory Disorders 75, no. : A459-A460.

Journal article
Published: 29 November 2017 in Journal of Breath Research
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Breath analyses have attracted substantial attention as screens for occupational environmental lung disease. The objective of this study was to develop breath tests for pneumoconiosis by analysing volatile organic compounds using an electronic nose. A case-control study was designed. We screened 102 subjects from a cohort of stone workers. After excluding three subjects with poorly controlled diabetes mellitus and one subject with asthma, 98 subjects were enrolled, including 34 subjects with pneumoconiosis and 64 healthy controls. We analysed the subjects' breath using an electronic nose with 32 nanocomposite sensors. Data were randomly split into 80% for model building and 20% for validation. Using a linear discriminate analysis, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were 67.9%, 88.0%, 80.8%, and 0.91, respectively, in the training set and 66.7%, 71.4%, 70.0%, and 0.86, respectively, in the test set. In subgroup analysis divided by smoking status, the AUROCs for current smokers, former smokers, and subjects who never smoked were 0.94, 0.93, and 0.99, respectively. In subgroup analysis divided by gender, the AUROCs for males and females were 0.95 and 0.99, respectively. Breath tests may have potential as a screen for pneumoconiosis. A multi-centre study is warranted, and the procedures must be standardized before clinical application.

ACS Style

Hsiao-Yu Yang; Hsin-Yi Peng; Che-Jui Chang; Pau-Chung Chen. Diagnostic accuracy of breath tests for pneumoconiosis using an electronic nose. Journal of Breath Research 2017, 12, 016001 .

AMA Style

Hsiao-Yu Yang, Hsin-Yi Peng, Che-Jui Chang, Pau-Chung Chen. Diagnostic accuracy of breath tests for pneumoconiosis using an electronic nose. Journal of Breath Research. 2017; 12 (1):016001.

Chicago/Turabian Style

Hsiao-Yu Yang; Hsin-Yi Peng; Che-Jui Chang; Pau-Chung Chen. 2017. "Diagnostic accuracy of breath tests for pneumoconiosis using an electronic nose." Journal of Breath Research 12, no. 1: 016001.

Journal article
Published: 17 October 2017 in Respiratory Research
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Lipid peroxidation plays an important role in the pathogenesis of pneumoconiosis. Volatile organic compounds (VOCs) generated from lipid peroxidation might be used to detect pneumoconiosis. The objective of this study was to develop a breath test for pneumoconiosis. A case-control study was designed. Breath and ambient air were analysed by gas chromatography/mass spectrometry. After blank correction to prevent contamination from ambient air, we used canonical discriminant analysis (CDA) to assess the discrimination accuracy and principal component analysis (PCA) to generate a prediction score. The prediction accuracy was calculated and validated using the International Classification of Radiographs of the Pneumoconiosis criteria combined with an abnormal pulmonary function test as a reference standard. We generated a receiver operator characteristic (ROC) curve and calculated the area under the ROC curve (AUC) to estimate the screening accuracy of the breath test. We enrolled 200 stone workers. After excluding 5 subjects with asthma and 16 subjects who took steroids or nonsteroidal anti-inflammatory drugs, a total of 179 subjects were used in the final analyses, which included 25 cases and 154 controls. By CDA, 88.8% of subjects were correctly discriminated by their exposure status and the presence of pneumoconiosis. After excluding the VOCs of automobile exhaust and cigarette smoking, pentane and C5-C7 methylated alkanes constituted the major VOCs in the breath of persons with pneumoconiosis. Using the prediction score generated from PCA, the ROC-AUC was 0.88 (95% CI = 0.80—0.95), and the mean ROC-AUC of 5-fold cross-validation was 0.90. The breath test had good accuracy for pneumoconiosis diagnosis. The analysis of breath VOCs has potential in the screening of pneumoconiosis for its non-invasiveness and high accuracy. We suggest that a multi-centre study is warranted and that all procedures must be standardized before clinical application.

ACS Style

Hsiao-Yu Yang; Ruei-Hao Shie; Che-Jui Chang; Pau-Chung Chen. Development of breath test for pneumoconiosis: a case-control study. Respiratory Research 2017, 18, 1 -8.

AMA Style

Hsiao-Yu Yang, Ruei-Hao Shie, Che-Jui Chang, Pau-Chung Chen. Development of breath test for pneumoconiosis: a case-control study. Respiratory Research. 2017; 18 (1):1-8.

Chicago/Turabian Style

Hsiao-Yu Yang; Ruei-Hao Shie; Che-Jui Chang; Pau-Chung Chen. 2017. "Development of breath test for pneumoconiosis: a case-control study." Respiratory Research 18, no. 1: 1-8.

Review
Published: 31 August 2017 in Canadian Respiratory Journal
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Objective. Talc is widely used in industrial applications. Previous meta-analyses of carcinogenic effects associated with inhaled talc included publications before 2004, with a lack of data in China, the largest talc-producing country. The safety of workers exposed to talc was unclear due to limited evidence. The objective of this study was to reevaluate the association between inhaled talc and lung cancer. Setting, Participants, and Outcome Measures. A meta-analysis was performed to calculate the meta-SMR of lung cancer. We searched the MEDLINE, EMBASE, CNKI, and Wanfang Data databases through March 2017. Data from observational studies were pooled using meta-analysis with random effects models. Results. Fourteen observational cohort studies (13 publications) were located via literature search. The heterogeneity of the included data was high ( I -squared = 72.9%). Pooling all the cohorts yielded a meta-SMR of 1.45 (95% CI: 1.22–1.72, p < 0.0001 ) for lung cancer among the study subjects exposed to talc. Subgroup analysis for asbestos contamination showed no significant difference in lung cancer death between subjects exposed to talc with and without asbestos ( p = 0.8680 ) , indicating that this confounding factor may have no significance. Conclusions. This study provides evidence that nonasbestiform talc might still increase the risk of lung cancer. Further epidemiological studies are required to evaluate the safety of workers with occupational talc exposure.

ACS Style

Che-Jui Chang; Yu-Kang Tu; Pau-Chung Chen; Hsiao-Yu Yang. Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies. Canadian Respiratory Journal 2017, 2017, 1 -12.

AMA Style

Che-Jui Chang, Yu-Kang Tu, Pau-Chung Chen, Hsiao-Yu Yang. Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies. Canadian Respiratory Journal. 2017; 2017 ():1-12.

Chicago/Turabian Style

Che-Jui Chang; Yu-Kang Tu; Pau-Chung Chen; Hsiao-Yu Yang. 2017. "Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies." Canadian Respiratory Journal 2017, no. : 1-12.

Conference paper
Published: 21 August 2017 in Poster Presentation
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Breath metabolites could reflect pathogenic events at the respiratory level and might be used to screen for the presence of occupational environmental lung diseases. The objective of this study was to estimate the accuracy of breath analysis for the diagnosis of pneumoconiosis using gas chromatography/mass spectrometry (GC/MS). A prospective study was design. We screened 200 subjects from a cohort of stone workers and their family members. Diagnosis of pneumoconiosis was made based on occupational history, the presence of abnormal pulmonary function, and parenchymal abnormalities consistent with pneumoconiosis on chest X-rays. After excluding subjects with asthma and those using steroids or taking nonsteroidal anti-inflammatory drugs on the examination day, we conducted a case-control study that enrolled 25 cases of pneumoconiosis and 154 controls. Breath and environmental air samples were collected and analysed by GC/MS. After subtraction of environmental volatile organic compounds (VOCs), the concentrations of VOCs in breath were used to discriminate between pneumoconiosis and controls. The discrimination accuracy was validated by both leave-one-out cross-validation and 5-fold cross-validation. The results showed that 94.4% of subjects were accurately classified and the cross-validated accuracy was 88.8%. The area under curve (AUC) for the diagnosis of pneumoconiosis was 0.9 (95% CI=0.8—1.0). Mean AUC of 5-fold cross-validation was 0.9. Breath test might have potential in the screening for pneumoconiosis; however, a multi-centre study is warranted to establish a reliable model and all procedures must be standardised before clinical application.

ACS Style

Hsiao-Yu Yang; Ruei-Hao Shie; Che-Jui Chang; Pau-Chung Chen. 0367 The diagnosis of pneumoconiosis using gas chromatography/mass spectrometry. Poster Presentation 2017, 74, A115 -A115.

AMA Style

Hsiao-Yu Yang, Ruei-Hao Shie, Che-Jui Chang, Pau-Chung Chen. 0367 The diagnosis of pneumoconiosis using gas chromatography/mass spectrometry. Poster Presentation. 2017; 74 ():A115-A115.

Chicago/Turabian Style

Hsiao-Yu Yang; Ruei-Hao Shie; Che-Jui Chang; Pau-Chung Chen. 2017. "0367 The diagnosis of pneumoconiosis using gas chromatography/mass spectrometry." Poster Presentation 74, no. : A115-A115.