Does leptin play a role in obesity–asthma relationship? The increase of asthma has paralleled the emerging obesity during the past decades (1). Several recent review articles have concluded that there is a positive association between obesity and asthma (2–4), but the underlying mecha- nisms have not yet been established. Several mechanisms have been postulated (3, 5). Firstly, obesity and asthma may share common genetic and environmental etiologies. Genetic and envi- ronmental factors may increase the risk of obesity concurrently with asthma (6, 7). Sec- ondly, obesity may increase the risk of asthma through its effects on other disease process, e.g. obesity is a risk factor for sleeping-disordered breathing and gastro-esophageal reflux disease (8, 9), and these two diseases are associated with an increased risk for asthma (10, 11). Thirdly, morbid obesity can reduce lung volume and airway diameter and increase asthma via mechanical mechanisms (2, 12). Last but not the least appealing hypothesis, obesity is charac- terized by increases in the serum concentrations of cytokines, chemokines, acute phase proteins and energy regulating hormones including leptin (13, 14). These mediators are produced by adipo- cytes and in general called adipokines. Although the precise mechanisms need to be determined, adipokines may alter T helper 1 (Th1)–T helper 2 (Th2) balance, immune tolerance, lung develop- ment, airway smooth muscle and airway respon- siveness (2, 15), which are associated with asthma development. Leptin is one of the adipose-derived energy regulating hormones and an obesity gene product (16). Circulating leptin is positively correlated with body fat percentage and body fat mass (17–19). In addition to its primary effects on energy regulation of inhibiting food intake and increasing energy expenditure, leptin has recently been identified to have pro-inflam- matory properties via the stimulation of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) from the adipose tissue (20, 21), and via the modulation of immunity to promote Th1 immune responses with increased production of interferon-c (IFN-c) (16, 22) (Fig. 1). Leptin has been correlated with the production of pro- inflammatory mediators, such as TNF-a, IL-6 Mai XM, Chen Y, Krewski D. Does leptin play a role in obesity– asthma relationship? Pediatr Allergy Immunol 2009: 20: 207–212. Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard The increase of asthma has paralleled the rising obesity during the past decades. Obesity is characterized by the increase of leptin in the circu- lation. Leptin is an obesity gene product, and it can stimulate the production of pro-inflammatory mediators, such as tumor necrosis factor (TNF)-a, interleukin (IL)-6 and interferon (IFN)-c. There is a link between leptin and asthma, especially in children. It remains un- clear however, if leptin is in the pathway of obesity–asthma relationship and if it plays a distinctive role in asthma in obese vs. non-obese sub- jects. Since leptin is in a positive feedback loop with the pro-inflam- matory cytokines such as TNF-a, there is a possibility that leptin is involved as a regulatory rather than an etiologic mechanism of asthma development. Weight loss is associated with decreased circulating leptin concentration in children. Weight control program may need to be considered in the treatment of asthma in obese children. Xiao-Mei Mai 1,2 , Yue Chen 3 and Daniel Krewski 1 1 McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada, 2 Department of Epidemiology, SINTEF Health, Trondheim, Norway, 3 Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada Key words: asthma; body mass index; leptin; obesity Dr Xiao-Mei Mai, PhD, Research Scientist, SINTEF Health, 7465 Trondheim, Norway Tel.: +4798245151 Fax: +4793070500 E-mail: xiao-mei.mai@sintef.no Accepted 3 September 2008 Abbreviations: BMI, body mass index; IFN-c, interferon-gam- ma; IL-6, interleukin-6; Th1, T helper 1; Th2, T helper 2; TNF- a, tumor necrosis factor-alpha. Pediatr Allergy Immunol 2009: 20: 207–212 DOI: 10.1111/j.1399-3038.2008.00812.x Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard PEDIATRIC ALLERGY AND IMMUNOLOGY 207