Elevated oxidative stress and steroid insensitivity in patients with asthma and high body fat percentage

Obesity is a risk factor for poor asthma control. Previous research suggests that patients with asthma and obesity have reduced responsiveness to corticosteroids. Recent studies indicate that body fat percentage may be more strongly associated with obesity-related diseases compared with body mass index. However, the relationship between body fat percentage and asthma, particularly regarding steroid sensitivity, remains unclear.

To investigate the association between body fat percentage and steroid sensitivity in patients with asthma and elucidate the potential mechanisms underlying this association.

Adult patients with asthma were enrolled and categorized into patients with high body fat percentage (HBF) and control groups. Peripheral blood mononuclear cells were isolated from the blood samples. These cells were cultured with dexamethasone followed by stimulation with tumor necrosis factor-α to assess the half-maximal inhibitory concentration of dexamethasone (IC₅₀-Dex). Serum adipocytokines and oxidative stress markers were also measured. The effects of metformin on steroid sensitivity and oxidative stress in peripheral blood mononuclear cells were evaluated ex vivo.

The HBF group exhibited significantly higher IC₅₀-Dex values than the control group. In the HBF group, IC₅₀-Dex correlated with the number of acute exacerbations per year and serum oxidative stress marker levels. Treatment with metformin significantly reduced both IC₅₀-Dex and oxidative stress marker levels in the HBF group.

Oxidative stress associated with increased body fat may contribute to impaired steroid sensitivity in patients with asthma. Metformin may improve steroid sensitivity by reducing oxidative stress, suggesting a potential therapeutic approach in this patient population.