The role of circulating serotonin in the development of chronic obstructive pulmonary disease

Kwok Wai LAU, Moira M. W. CHAN-YEUNG, Benjamin H. K. YIP, Amy H. K. CHEUNG, Mary S. M. IP, Judith C. W. Mak, COPD Study Group of the Hong Kong Thoracic Society

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Background: Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age. 

Methods: The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA). 

Results: The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108). 

Conclusion: Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease. Copyright © 2012 Lau et al.

Original languageEnglish
Article numbere31617
JournalPLoS One
Issue number2
Publication statusPublished - 03 Feb 2012


Pulmonary diseases
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
Tobacco Products
smoking (habit)
Serotonin Plasma Membrane Transport Proteins
Healthy Volunteers
risk factors


Lau, W. K. W., Chan-Yeung, M. M. W., Yip, B. H. K., Cheung, A. H. K., Ip, M. S. M., Mak, J. C. W., & COPD Study Group of the Hong Kong Thoracic Society (2012). The role of circulating serotonin in the development of chronic obstructive pulmonary disease. PLoS One, 7(2). Retrieved from