Mechanisms underlying the association between obesity and asthma are not well understood. Obesity is characterised by chronic inflammation and adipose tissue, comprising up to 50% pro-inflammatory cells, produces many pro-inflammatory cytokines and hormones (adipokines). Enhanced systemic inflammation might provide the causal link between obesity and asthma. Although there are good mechanistic data that obesity can augment innate immune function and promote immune dysregulation by reducing regulatory T cell (Treg) numbers there is little work in this area in relation to asthma.Methods
A case-control study is being conducted examining six groups of pre-menopausal women (n=120): normal weight (BMI 20–25 kg/m2), overweight (BMI 25–30 kg/m2) and obese individuals (BMI >30 kg/m2) with and without asthma. Asthma diagnosis was physician confirmed, and severity graded. Measures of adiposity, lung function and blood were collected during menstruation. Automated haematology analysis was used to quantify major cell types and chemiluminesence to measure whole blood reactive oxygen species generation following stimulation. Flow cytometry was used to examine major lymphocyte subtypes including Treg cells. A number of circulating cytokines and adipokines will be measured on sample collection completion.Results
Interim analysis of 36 individuals revealed a significant increase in circulating total leucocytes with increasing BMI which is more pronounced in asthmatics compared with controls (p=0.022). This appears to be due to a significant increase in neutrophils (Abstract P208 figure 1, (p=0.018)). In parallel, reactive oxygen species generation increased with each BMI category (p=0.026). Furthermore, the eosinophil count dropped significantly with increasing BMI in the asthma patients (p=0.045).Conclusion
Preliminary data from this study suggests that obesity is associated with systemic inflammation resulting in increasing levels of circulating neutrophils and that this is more marked in asthmatics than controls. This is in keeping with recent work showing increased neutrophils locally in the sputum of obese asthmatics. Our findings could explain the reduced inhaled corticosteroid efficacy observed in this asthma phenotype.