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Analysis Of Heterocyclic Amines In Meat Products By Liquid Chromatography – Tandem Mass Spectrometry, S.-H. Jian, P.-J. Yeh, C.-H. Wang, H.-C. Chen, S.-F. Chen 2020 Taiwan Food and Drug Administration

Analysis Of Heterocyclic Amines In Meat Products By Liquid Chromatography – Tandem Mass Spectrometry, S.-H. Jian, P.-J. Yeh, C.-H. Wang, H.-C. Chen, S.-F. Chen

Journal of Food and Drug Analysis

Heterocyclic amines (HCAs), a class made up of more than 25 compounds, are unintended hazardous substances that are generated by the heating or processing of proteinaceous foods at high temperatures. The International Agency for Research on Cancer (IARC) has classified four such HCAs (IQ, MeIQ, MeIQx, and PhIP) as being probable or possible human carcinogens. In this study, two sample preparation strategies, liquid–liquid extraction (LLE) with solid-phase extraction (SPE) and a rapid, easy, cheap, effective, rugged, and safe extraction (QuEChERS) method, were investigated for the determination of 11 types of HCAs in meat products by LC-MS/MS. The HCAs in the …


Development Of Biomarkers Of Genitourinary Cancer Using Mass Spectrometry-Based Clinical Proteomics, Y.-T. Chen, C.-H. Tsai, C.-L. Chen, J.-S. Yu, Y.-H. Chang 2020 Taiwan Food and Drug Administration

Development Of Biomarkers Of Genitourinary Cancer Using Mass Spectrometry-Based Clinical Proteomics, Y.-T. Chen, C.-H. Tsai, C.-L. Chen, J.-S. Yu, Y.-H. Chang

Journal of Food and Drug Analysis

Prostate, bladder and kidney cancer are the three most common types of genitourinary cancer in the world. Of these, prostate and bladder cancers are within the top 10 most common cancers in men. Notably, kidney cancer causes no obvious symptoms in the early stages. To satisfy clinical-management requirements, researchers have developed numerous biomarkers by applying proteomic approaches using clinical serum, urine and tissue specimens, as well as cell and animal models. Through application of biomarker pipeline protocols, including discovery, verification and validation phases, and mass-spectrometric based proteomic platforms coupled with multiplexed quantification assays, these studies have led to recent rapid …


Using Ambient Mass Spectrometry And Lc–Ms/Ms For The Rapid Detection And Identification Of Multiple Illicit Street Drugs, C.-H. Chiang, H.-H. Lee, B.-H. Chen, Y.-C. Lin, Y.-Y. Chao, Y.-L. Huang 2020 Taiwan Food and Drug Administration

Using Ambient Mass Spectrometry And Lc–Ms/Ms For The Rapid Detection And Identification Of Multiple Illicit Street Drugs, C.-H. Chiang, H.-H. Lee, B.-H. Chen, Y.-C. Lin, Y.-Y. Chao, Y.-L. Huang

Journal of Food and Drug Analysis

In this study the recently developed technique of thermal desorption electrospray ionization/mass spectrometry (TD–ESI/MS) was applied to the rapid analysis of multiple controlled substances. With the reallocation of mass spectral resources [from a standard ESI source coupled with liquid chromatography (LC) to an ambient TD–ESI source], this direct-analysis technique allows the identification of a wider range of illicit drugs through a dual-working mode (pretreatment-free qualitative screening/conventional quantitative confirmation). Through 60-MRM (multiple reaction monitoring) analysis—in which the MS/MS process was programmed to sequentially scan 60 precursor ion/product ion transitions and, thereby, identify 30 compounds (two precursor/product ion transitions per compound)—of a …


Measuring Serum Total And Free Indoxyl Sulfate And P-Cresyl Sulfate In Chronic Kidney Disease Using Uplc-Ms/Ms, C.-N. Lin, I.-W. Wu, Y.-F. Huang, S.-Y. Peng, Y.-C. Huang, H.-C. Ning 2020 Taiwan Food and Drug Administration

Measuring Serum Total And Free Indoxyl Sulfate And P-Cresyl Sulfate In Chronic Kidney Disease Using Uplc-Ms/Ms, C.-N. Lin, I.-W. Wu, Y.-F. Huang, S.-Y. Peng, Y.-C. Huang, H.-C. Ning

Journal of Food and Drug Analysis

Chronic kidney disease (CKD) is a complex disorder that affects multiple organs and increases the risk of cardiovascular complications. CKD affects approximately 12% of the population in Taiwan. Loss of kidney function leads to accumulation of potentially toxic compounds such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS), two protein-bound uremic solutes that can stimulate the progression of CKD. The aim of this study was to assess whether IS and pCS levels were correlated with CKD stage. We developed and validated a method for quantitating total and free IS and pCS in serum by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). …


Exposure Marker Discovery Of Di-2(Propylheptyl) Phthalate Using Ultra-Performance Liquid Chromatography-Mass Spectrometry And A Rat Model, C.-L. Shih, J.-Y. Hsu, C.-P. Tien, Y.-N. Chung, V.G. Zgoda, P.-C. Liao 2020 Taiwan Food and Drug Administration

Exposure Marker Discovery Of Di-2(Propylheptyl) Phthalate Using Ultra-Performance Liquid Chromatography-Mass Spectrometry And A Rat Model, C.-L. Shih, J.-Y. Hsu, C.-P. Tien, Y.-N. Chung, V.G. Zgoda, P.-C. Liao

Journal of Food and Drug Analysis

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite …


Chemical Isotope Labeling Liquid Chromatography Mass Spectrometry For Investigating Acute Dietary Effects Of Cow Milk Consumption On Human Urine Metabolome, D. Mung, L. Li 2020 Taiwan Food and Drug Administration

Chemical Isotope Labeling Liquid Chromatography Mass Spectrometry For Investigating Acute Dietary Effects Of Cow Milk Consumption On Human Urine Metabolome, D. Mung, L. Li

Journal of Food and Drug Analysis

Biomarker discovery has been increasingly important in the field of metabolomics for the detection and understanding of diseases. Of the many biofluids available for metabolomics, urine is a preferred option as it is non-invasive to collect and contains a wide range of metabolites reflective of the health status of the testing individual. However, urine also contains many exogenous metabolites which are introduced through various sources such as diet. This complicates the data interpretation when searching the metabolome for disease-related endogenous metabolites. Since diet is difficult to control, this work aims to study the acute effects of diet (particularly cow milk) …


Quantitation Of Serum 25(Oh)D2 And 25(Oh)D3 Concentrations By Liquid Chromatography Tandem Mass Spectrometry In Patients With Diabetes Mellitus, Y.-C. Lin, H.-H. Lee, S.-C. Tseng, K.-D. Lin, L.-P. Tseng, J.-F. Lee, Y.-H. Lee, B.-H. Chen 2020 Taiwan Food and Drug Administration

Quantitation Of Serum 25(Oh)D2 And 25(Oh)D3 Concentrations By Liquid Chromatography Tandem Mass Spectrometry In Patients With Diabetes Mellitus, Y.-C. Lin, H.-H. Lee, S.-C. Tseng, K.-D. Lin, L.-P. Tseng, J.-F. Lee, Y.-H. Lee, B.-H. Chen

Journal of Food and Drug Analysis

Vitamin D has been considered to regulate calcium and phosphorus homeostasis and to preserve skeletal integrity. Serum 25-hydroxyvitamin D (25(OH)D) is the best indicator of vitamin D levels. The association of serum 25(OH)D deficiency with increased risk of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) is controversial. We investigated serum 25(OH)D 2 and 25(OH)D 3 levels in diabetes patients by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum 25(OH)D2 and 25(OH)D3 levels were measured with liquid chromatography tandem mass spectrometry in electrospray ionization positive mode. Chromatograms were separated using an ACE5 C18 column on a gradient of methanol. …


Rapid Identification Of Herbal Toxins Using Electrospray Laser Desorption Ionization Mass Spectrometry For Emergency Care, H. Su, K.-T. Liu, B.-H. Chen, Y.-P. Lin, Y.-M. Jiang, Y.-H. Tsai, F.-R. Chang, J. Shiea, C.-W. Lee 2020 Taiwan Food and Drug Administration

Rapid Identification Of Herbal Toxins Using Electrospray Laser Desorption Ionization Mass Spectrometry For Emergency Care, H. Su, K.-T. Liu, B.-H. Chen, Y.-P. Lin, Y.-M. Jiang, Y.-H. Tsai, F.-R. Chang, J. Shiea, C.-W. Lee

Journal of Food and Drug Analysis

The unintentional ingestion of toxic compounds in herbs is not uncommon in many parts of the world. To provide timely and life-saving care in the emergency department, it is essential to develop a point-of-care analytical method that can rapidly identify these toxins in herbs. Since electrospray laser desorption ionization mass spectrometry (ELDI/MS) has been successfully used to characterize non-volatile chemical compounds without sample preparation, it was used to identify toxic herbal compounds in this study. The herbal toxins were collected either by sweeping a metallic probe across the surface of a freshly cut herb section or by directly sampling extracts …


Complete Mapping Of Disulfide Linkages For Etanercept Products By Multi-Enzyme Digestion Coupled With Lc-Ms/Ms Using Multi-Fragmentations Including Cid And Etd, L.-J. Huang, C.-W. Chiang, S.-L. Chen, S.-Y. Wei, S.-H. Chen 2020 Taiwan Food and Drug Administration

Complete Mapping Of Disulfide Linkages For Etanercept Products By Multi-Enzyme Digestion Coupled With Lc-Ms/Ms Using Multi-Fragmentations Including Cid And Etd, L.-J. Huang, C.-W. Chiang, S.-L. Chen, S.-Y. Wei, S.-H. Chen

Journal of Food and Drug Analysis

The disulfide linkages of two etanercept products, Enbrel® (innovator drug) and TuNEX®, were characterized and compared using a multi-fragmentation approach consisting of electron transfer dissociation (ETD) and collision induced dissociation (CID) in combination with multi-enzyme digestion protocols (from Lys-C, trypsin, Glu-C, and PNGase F). Multi-fragmentation approach allowed multi-disulfide linkages contained in a peptide to be un-ambiguously assigned based on the cleavage of both the disulfide and the backbone linkages in a MS 3 schedule. New insights gained using this approach were discussed. A total of 29 disulfides, Cys18-Cys31, Cys32-Cys45, Cys35-Cys53, Cys56-Cys71, Cys74-Cys88, Cys78-Cys-96, Cys98-Cys104, Cys112-Cys121, Cys115-Cys139, Cys-142-Cys157, Cys163-Cys178 in TNFR …


Targeting Amine- And Phenol-Containing Metabolites In Urine By Dansylation Isotope Labeling And Liquid Chromatography Mass Spectrometry For Evaluation Of Bladder Cancer Biomarkers, Y.-T. Chen, H.-C. Huang, Y.-J. Hsieh, S.-H. Fu, L. Li, C.-L. Chen, L.J. Chu, J.-S. Yu 2020 Taiwan Food and Drug Administration

Targeting Amine- And Phenol-Containing Metabolites In Urine By Dansylation Isotope Labeling And Liquid Chromatography Mass Spectrometry For Evaluation Of Bladder Cancer Biomarkers, Y.-T. Chen, H.-C. Huang, Y.-J. Hsieh, S.-H. Fu, L. Li, C.-L. Chen, L.J. Chu, J.-S. Yu

Journal of Food and Drug Analysis

Metabolomics is considered an effective approach for understanding metabolic responses in complex biological systems. Accordingly, it has attracted increasing attention for biomarker discovery, especially in cancer. In this study, we used a non-invasive method to evaluate four urine metabolite biomarker candidates—o-phosphoethanolamine, 3-amio-2-piperidone, uridine and 5-hydroxyindoleactic acid—for their potential as bladder cancer diagnostic biomarkers. To analyze these targeted amine- and phenol-containing metabolites, we used differential 12 C 2 -/ 13 C 2 -dansylation labeling coupled with liquid chromatography/tandem mass spectrometry, which has previously been demonstrated to exhibit high sensitivity and reproducibility. Specifically, we used ultra-performance liquid chromatography (UPLC) coupled with high-resolution …


Glycoproteomic Identification Of Novel Plasma Biomarkers For Oral Cancer, S.-C. Chang, W.-L. Lin, Y.-F. Chang, C.-T. Lee, J.-S. Wu, P.-H. Hsu, C.-F. Chang 2020 Taiwan Food and Drug Administration

Glycoproteomic Identification Of Novel Plasma Biomarkers For Oral Cancer, S.-C. Chang, W.-L. Lin, Y.-F. Chang, C.-T. Lee, J.-S. Wu, P.-H. Hsu, C.-F. Chang

Journal of Food and Drug Analysis

Oral cancer with high incidence rates is occurring in many countries including in India, Pakistan, Bangladesh, Sri Lanka and Taiwan. Smoking, alcoholism, and betel nut chewing are considered to be the main risk factors for oral cancer. Further, deaths from oral cancer have increased year by year. Although several oral cancer-associated biomarkers have been reported, very few useful biomarkers have been applied for early diagnosis. Therefore, the investigation of oral cancer-specific biomarkers is urgently needed. We previously investigated N-glycomes of oral cancer cells and patient plasma. We found that both mRNA levels of FUT8 and core-fucosylated glycoproteins increase in cases …


Reduction Of Aluminum Ion Neurotoxicity Through A Small Peptide Application – Nap Treatment Of Alzheimer's Disease, M.-H. Yang, S.-C. Chen, Y.-F. Lin, Y.-C. Lee, M.-Y. Huang, K.-C. Chen, H.-Y. Wu, P.-C. Lin, I. Gozes, Y.-C. Tyan 2020 Taiwan Food and Drug Administration

Reduction Of Aluminum Ion Neurotoxicity Through A Small Peptide Application – Nap Treatment Of Alzheimer's Disease, M.-H. Yang, S.-C. Chen, Y.-F. Lin, Y.-C. Lee, M.-Y. Huang, K.-C. Chen, H.-Y. Wu, P.-C. Lin, I. Gozes, Y.-C. Tyan

Journal of Food and Drug Analysis

Alzheimer's disease (AD) is the most common cause of dementia in late life. It is difficult to precisely diagnose AD at early stages, making biomarker search essential for further developments. The objective of this study was to identify protein biomarkers associated with aluminum ions toxicity (AD-like toxicity) in a human neuroblastoma cell model, SH-SY5Y and assess potential prevention by NAP (NAPVSIPQ). Complete proteomic techniques were implemented. Four proteins were identified as up-regulated with aluminum ion treatment, CBP80/20-dependent translation initiation factor (CTIF), Early endosome antigen 1 (EEA1), Leucine-rich repeat neuronal protein 4 (LRRN4) and Phosphatidylinositol 3-kinase regulatory subunit beta (PI3KR2). Of …


Direct And Rapid Characterization Of Illicit Drugs In Adulterated Samples Using Thermal Desorption Electrospray Ionization Mass Spectrometry, S.-C. Cheng, Y.-D. Tsai, C.-W. Lee, B.-H. Chen, J. Shiea 2020 Taiwan Food and Drug Administration

Direct And Rapid Characterization Of Illicit Drugs In Adulterated Samples Using Thermal Desorption Electrospray Ionization Mass Spectrometry, S.-C. Cheng, Y.-D. Tsai, C.-W. Lee, B.-H. Chen, J. Shiea

Journal of Food and Drug Analysis

Foods and drinks have been adulterated with illicit drugs to facilitate criminal activities. Unfortunately, conventional analytical methods are incapable of rapidly characterizing these drugs in samples, as serious interferences from sample matrices must be removed through tedious and time-consuming pretreatment. Ambient ionization mass spectrometry (AMS) generally does not require sample pretreatment and is thus a suitable tool for directly and rapidly detecting illicit drugs in samples in different physical states. In this study, thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS), an AMS technique, was utilized to efficiently characterize illicit drugs spiked in samples including drinks, powders, and jelly candies. To …


Using Gas Chromatography And Mass Spectrometry To Determine 25-Hydroxyvitamin D Levels For Clinical Assessment Of Vitamin D Deficiency, M.-Y. Yang, C.-Y. Huang, T.H.T. Chiu, K.-C. Chang, M.-N. Lin, L.-Y. Chen, A. Hu 2020 Taiwan Food and Drug Administration

Using Gas Chromatography And Mass Spectrometry To Determine 25-Hydroxyvitamin D Levels For Clinical Assessment Of Vitamin D Deficiency, M.-Y. Yang, C.-Y. Huang, T.H.T. Chiu, K.-C. Chang, M.-N. Lin, L.-Y. Chen, A. Hu

Journal of Food and Drug Analysis

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out …


Current Status Of Maldi-Tof Mass Spectrometry In Clinical Microbiology, T.-Y. Hou, C. Chiang-Ni, S.-H. Teng 2020 Taiwan Food and Drug Administration

Current Status Of Maldi-Tof Mass Spectrometry In Clinical Microbiology, T.-Y. Hou, C. Chiang-Ni, S.-H. Teng

Journal of Food and Drug Analysis

Mass spectrometry (MS) is a type of analysis used to determine what molecules make up a sample, based on the mass spectrum that are created by the ions. Mass spectrometers are able to perform traditional target analyte identification and quantitation; however, they may also be used within a clinical setting for the rapid identification of bacteria. The causative agent in sepsis is changed over time, and clinical decisions affecting the management of infections are often based on the outcomes of bacterial identification. Therefore, it is essential that such identifications are performed quickly and interpreted correctly. Matrix-assisted laser desorption/ionization-time of flight …


Utilizing Proteomic Approach To Identify Nuclear Translocation Related Serine Kinase Phosphorylation Site Of Gnmt As Downstream Effector For Benzo[A]Pyrene, M.-H. Yang, C.-C. Liao, J.-H. Hung, X.-T. Lai, C.-H. Yen, Y.-M.A. Chen 2020 Taiwan Food and Drug Administration

Utilizing Proteomic Approach To Identify Nuclear Translocation Related Serine Kinase Phosphorylation Site Of Gnmt As Downstream Effector For Benzo[A]Pyrene, M.-H. Yang, C.-C. Liao, J.-H. Hung, X.-T. Lai, C.-H. Yen, Y.-M.A. Chen

Journal of Food and Drug Analysis

Glycine N-methyltransferase (GNMT) protein is highly expressed in certain tissues, such as liver, pancreas, and prostate. GNMT serves multiple roles which include a methyl group transfer enzyme and a liver tumor suppressor. Benzo(a)pyrene (BaP), a family member of polycyclic aromatic hydrocarbon (PAH), is a known environmental carcinogen found in coal tar, tobacco smoke, barbecued food and incomplete combustion of auto fuel. BaP recruits cytochrome P450 to transform itself into benzo(a)pyrene-7,8-diol-9,10-epoxide (B(a)PDE), which covalently interacts with DNA causing tumorigenesis. BaP can be detoxified through GNMT and induces GNMT translocation into the cellular nucleus. GNMT translocation is accompanied by phosphorylation, but the …


Detection Of Bpde-Dna Adducts In Human Umbilical Cord Blood By Lc-Ms/Ms Analysis, L. Guo, X. Jiang, H.-Y. Tian, S.-J. Yao, B.-Y. Li, R.-J. Zhang, S.-S. Zhang, X. Sun 2020 Taiwan Food and Drug Administration

Detection Of Bpde-Dna Adducts In Human Umbilical Cord Blood By Lc-Ms/Ms Analysis, L. Guo, X. Jiang, H.-Y. Tian, S.-J. Yao, B.-Y. Li, R.-J. Zhang, S.-S. Zhang, X. Sun

Journal of Food and Drug Analysis

Benzo [a]pyrene (BaP) is a model compound for the study of polycyclic aromatic hydrocarbon (PAH) carcinogenesis. Upon metabolism, BaP is metabolized to the ultimate metabolite, BaP trans-7,8-diol-anti-9,10-epoxide (BPDE), that reacts with cellular DNA to form BPDE-dG adducts responsible for BaP-induced mutagenicity, carcinogenicity, and teratogenicity. In this study, we employed our developed LC-MS/MS method to detect and quantity BPDE-dG adducts present in 42 normal human umbilical cord blood samples and 42 birth defect cases. We determined that there is no significant difference in the level of BPDE-dG formation between the normal and birth defect groups. This represents the first time to …


A Highly Sensitive Ultra-High Performance Liquid Chromatography/Tandem Mass Spectrometry Method With In-Source Fragmentation For Rapid Quantification Of Raspberry Ketone, B. Yuan, D. Zhao, R. Du, D. Kshatriya, N.T. Bello, J.E. Simon, Q. Wu 2020 Taiwan Food and Drug Administration

A Highly Sensitive Ultra-High Performance Liquid Chromatography/Tandem Mass Spectrometry Method With In-Source Fragmentation For Rapid Quantification Of Raspberry Ketone, B. Yuan, D. Zhao, R. Du, D. Kshatriya, N.T. Bello, J.E. Simon, Q. Wu

Journal of Food and Drug Analysis

Raspberry ketone (RK) is the characteristic aromatic compound in raspberry (Rubus idaeus L.) with wide applications as food additive and anti-obesity agent. However, quantification of RK has presented difficulties in MS detection and reliable LC-MS method for RK analysis in literature is in limit to date. In order to facilitate quality control of raspberry derived products and RK metabolomics study, this study aimed to develop a validated and sensitive UHPLC-MS/MS method. Strong in-source fragmentation was noted and the fragmental ion of 107 m/z produced was selected as the precursor ion for MRM detection, and as such the electrospray ionization performance …


Nelumbo Nucifera Leaves Extract Attenuate The Pathological Progression Of Diabetic Nephropathy In High-Fat Diet-Fed And Streptozotocin-Induced Diabetic Rats, H.-W. Chen, M.-Y. Yang, T.-W. Hung, Y.-C. Chang, C.-J. Wang 2020 Taiwan Food and Drug Administration

Nelumbo Nucifera Leaves Extract Attenuate The Pathological Progression Of Diabetic Nephropathy In High-Fat Diet-Fed And Streptozotocin-Induced Diabetic Rats, H.-W. Chen, M.-Y. Yang, T.-W. Hung, Y.-C. Chang, C.-J. Wang

Journal of Food and Drug Analysis

Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Lotus (Nelumbo nucifera) possesses antioxidative and anticancer properties. The present study aimed to investigate the antidiabetic and renoprotective effects of N. nucifera leaf extract (NLE) in a rat model of type 2 diabetic mellitus. Male Sprague–Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with NLE at dosages of 0.5% and 1% (w/w) daily for 6 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and …


Risk Of Adverse Cardiovascular Events With Use Of Inhaled Long-Acting Bronchodilators In Management Of Chronic Obstructive Pulmonary Disease, M.-T. Wang, J.-H. Lai, C.-L. Tsai, J.-T. Liou 2020 Taiwan Food and Drug Administration

Risk Of Adverse Cardiovascular Events With Use Of Inhaled Long-Acting Bronchodilators In Management Of Chronic Obstructive Pulmonary Disease, M.-T. Wang, J.-H. Lai, C.-L. Tsai, J.-T. Liou

Journal of Food and Drug Analysis

Inhaled long-acting bronchodilators, including long-acting β2 agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are the mainstay therapy in the treatment of chronic obstructive pulmonary disease (COPD), a disease that poses a heavy burden on morbidity and mortality worldwide. Use of LABAs and LAMAs in patients with COPD, however, has been concerned about an increased risk of adverse cardiovascular events, despite inconsistent findings reported from randomized controlled trials (RCTs) and observational studies. In this review, we detailed the relevant evidence generated from RCTs and observational studies with respect to the risk of cardiovascular disease with use of LABAs and LAMAs in …


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