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Abstract
BackgroundBetel 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.MethodsWe 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.ResultsA 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).ConclusionBetel chewing is associated with asthma in this population, with arecoline induction of eotaxin-1 supported as a plausible causal pathway.
Highlights
Betel nut is a common substance used by an estimated 600 million people worldwide [1], in India, the SouthPacific Islands and Southeast Asia
Alcohol consumption behavior was not different between the two groups, but smoking and betel chewing were more common in the case group
BMI, smoking, betel chewing and eotaxin-1 levels were associated with asthma
Summary
Betel nut is a common substance used by an estimated 600 million people worldwide [1], in India, the SouthPacific Islands and Southeast Asia. The main alkaloids contained in areca nut are arecoline and arecaidine, which have been supported as exposure biomarkers for a the habit of betel chewing [8]. Considering the widespread exposure and potential risk, few studies have investigated the relationship between betel chewing and asthma. Taylor et al reported that two patients hospitalized with asthma had been chewing betel nut immediately before the attacks, and they performed a double-blind challenge test of arecoline inhalation, which was found to cause bronchoconstriction in six of seven people with asthma and one of six healthy controls [10]. 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
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