title: Betel chewing and arecoline affects eotaxin-1, asthma and lung function.
abstract: BACKGROUND
  Betel nut is commonly used in many countries. Despite evidence suggesting an association with asthma, few studies have investigated the connection between betel nut use and asthma; thus, the underlying mechanism for the association with asthma is also unclear. The aim of this study was to investigate the association between betel chewing and asthma as well as the associations of plasma arecoline (a biomarker for exposure) and eotaxin-1 (a potential mediator) with asthma and lung function.
  
  
  METHODS
  We recruited 600 hospital-based asthmatic patients and 1200 age- and gender-matched community controls in southern Taiwan. To clarify the mechanism of action for eotaxin-1 in the association between betel chewing and asthma, we also designed an in vitro experiment to study the functional associations between arecoline exposure and eotaxin-1 levels.
  
  
  RESULTS
  A significant association was found between asthma and current betel chewing (adjusted odds ratio 2.05, 95% CI = 1.12-3.76), which was independent of potential confounders but was attenuated following adjustment for eotaxin-1. Arecoline and eotaxin-1 levels were positively correlated (Spearman r = 0.303, p = 0.02), while arecoline and arecaidine were negatively correlated with lung function. Functionally, arecoline alone does not induce eotaxin-1 release in vitro from dermal and gingival fibroblasts. However, in the presence of IL-4 and TNF-alpha, arecoline at 100 μg/ml induced more eotaxin-1 release than arecoline at 0 μg/ml (2700±98 pg/ml vs 1850±142 pg/ml, p = 0.01 in dermal fibroblast cells, and 1489±78 pg/ml vs 1044±95 pg/ml, p = 0.03 in gingival fibroblast cells, respectively).
  
  
  CONCLUSIONS
  Betel chewing is associated with asthma in this population, with arecoline induction of eotaxin-1 supported as a plausible causal pathway.
authors.affiliation: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsu-Nai
authors.initials: TN
authors.lastname: Wang
authors.affiliation: Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine and Geriatric Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsai-Hui
authors.initials: TH
authors.lastname: Duh
authors.affiliation: Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ping-Ho
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chau-Chyun
authors.initials: CC
authors.lastname: Sheu
authors.affiliation: Department of Psychiatry, School of Medicine, Institute of Medicine, Chung Shan Medical University, The Department of Psychiatry, Chung Shan Medical University Hospital, Taichung. Taiwan; King's College London, Institute of Psychiatry, London, United Kingdom.
authors.forename: Vincent Chin-Hung
authors.initials: VC
authors.lastname: Chen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Universidade Federal de São Paulo - Psychobiology Department, São Paulo, Brazil.
authors.forename: Cleusa P
authors.initials: CP
authors.lastname: Ferri
authors.affiliation: King's College London, Institute of Psychiatry, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000378:metabolism*; D001249:Asthma / Q000209:etiology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008409:Mastication; D012129:Respiratory Function Tests
chemical_list: D054413:Chemokine CCL11; D001115:Arecoline