Betel Chewing and Arecoline Affects Eotaxin-1, Asthma and Lung Function

National Health Research Institutes National Science Council, Taiwan National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust King's College London 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 mg/ml induced more eotaxin-1 release than arecoline at 0 mu g/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).Conclusion: Betel chewing is associated with asthma in this population, with arecoline induction of eotaxin-1 supported as a plausible causal pathway. Kaohsiung Med Univ, Coll Hlth Sci, Dept Publ Hlth, Kaohsiung, Taiwan Kaohsiung Med Univ, Ctr Excellence Environm Med, Kaohsiung, Taiwan Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Coll Med, Dept Internal Med,Div Pulm & Crit Care Med & Geri, Kaohsiung, Taiwan Chang Gung Univ, Chang Gung Mem Hospital, Coll Med, Med Ctr,Dept Med,Div Pulm & Critical Care Med, Kaohsiung, Taiwan Kaohsiung Med Univ, Dept Med & Appl Chem, Kaohsiung, Taiwan Kaohsiung Chang Gung Mem Hosp, Dept Dermatol, Kaohsiung, Taiwan Chang Gung Univ, Coll Med, Kaohsiung, Taiwan Kaohsiung Med Univ, Coll Dent Med, Sch Dent, Kaohsiung, Taiwan China Med Univ Hosp, Environment Omics Dis Res Ctr, Taichung, Taiwan China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Coll Med, Fac Med,Dept Internal Med,Div Pulm & Crit Care Me, Kaohsiung, Taiwan Chung Shan Med Univ, Chung Shan Med Univ Hosp, Sch Med, Inst Med,Dept Psychiat, Taichung, Taiwan Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil Kings Coll London, Inst Psychiat, London, England Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil National Health Research Institutes: NHRI-CN-PD9611P National Science Council, Taiwan: NSC96-2314-B-037-040-MY3 National Science Council, Taiwan: NSC100-2314-B-037-025-MY3 Web of Science