Association of antieosinophil therapy with decreased body mass index in patients with severe asthma

Abstract

The type 2 high endotype of asthma with adult onset is often characterized by severe, persistent, steroid-refractory eosinophilic inflammation. Interleukin 5 (IL-5) is a pivotal cytokine for eosinophil survival. The amelioration of eosinophilic inflammation through anti-IL-5 therapies (mepolizumab, reslizumab, and ben-ralizumab) reduces exacerbations and improves control is and well tolerated overall.

Unraveling the connection between eosinophils and obesity

“…In humans, reducing or depleting eosinophils in asthma reduced body weight in thin and overweight asthma subjects 25,26 . Although these studies were not designed to test the role of eosinophils, this data does not support a protective role for eosinophils in obesity in humans.…”

“…Kuruvilla et al. found in a small study, over 6 months, that anti‐IL‐5 therapy was associated with a mild but significant decrease in BMI in patients with severe asthma 25 . However, this particular study was not randomized or placebo controlled and lacked other measurements related to obesity including body fat and glucose tolerance 25 .…”

“…The decrease in body weight on anti‐IL‐5 or anti‐IL‐5 receptor treatment may, therefore, be due to a reduction in steroid use or an increase in physical activity. Additionally, eosinophils were only measured in blood, not in body fat 25,26 . This is important because, animal studies have demonstrated that adipose eosinophils, rather than circulating eosinophils, promote leanness 9 .…”

Obesity-associated asthma in childhood

“…The macrolide azithromycin could reduce the rate of exacerbation in adult patients with non-eosinophilic asthma [ 52 , 80 ]. Interestingly, a reduction in BMI was observed in asthma under anti-IL-5 therapy, which was associated with the role of eosinophils in the homeostasis of these cells in adipose tissue [ 83 ].…”

“…Initial data in adults have shown that metformin may also improve asthma exacerbations in patients with metabolic syndrome [ 86 ]. The role of anti-IL-5 therapy needs further evaluation [ 53 , 83 ], and an anti-IL-1 antibody is still being investigated in clinical trials [ 52 ]. Anti-thymic stromal lymphopoietin (TSLP) therapy, for example with tezepelumab, is also a possible approach [ 87 ].…”