To Masako, Arimoto Yoshihito, Honda Natsue, Furusho Naho, Kinouchi Toru, Takeshita Yuichiro, Haruki Kosuke, To Yasuo
Department of Laboratory Medicine, Dokkyo Medical University, Saitama Medical Center, Saitama, Japan; Department of Respiratory Medicine, The Fraternity Memorial Hospital, Tokyo, Japan.
Department of Laboratory Medicine, Dokkyo Medical University, Saitama Medical Center, Saitama, Japan.
Ann Allergy Asthma Immunol. 2025 Jun;134(6):664-670. doi: 10.1016/j.anai.2025.03.009. Epub 2025 Mar 15.
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 (IC-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 IC-Dex values than the control group. In the HBF group, IC-Dex correlated with the number of acute exacerbations per year and serum oxidative stress marker levels. Treatment with metformin significantly reduced both IC-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.
肥胖是哮喘控制不佳的一个风险因素。先前的研究表明，哮喘合并肥胖患者对皮质类固醇的反应性降低。近期研究表明，与体重指数相比，体脂百分比可能与肥胖相关疾病的关联更为密切。然而，体脂百分比与哮喘之间的关系，尤其是在类固醇敏感性方面，仍不明确。
探讨哮喘患者体脂百分比与类固醇敏感性之间的关联，并阐明这种关联潜在的机制。
纳入成年哮喘患者，分为高体脂百分比（HBF）患者组和对照组。从血样中分离外周血单个核细胞。这些细胞用地塞米松培养，随后用肿瘤坏死因子-α刺激，以评估地塞米松的半数最大抑制浓度（IC-Dex）。还检测了血清脂肪细胞因子和氧化应激标志物。在体外评估二甲双胍对外周血单个核细胞中类固醇敏感性和氧化应激的影响。
HBF组的IC-Dex值显著高于对照组。在HBF组中，IC-Dex与每年急性加重次数及血清氧化应激标志物水平相关。二甲双胍治疗显著降低了HBF组的IC-Dex和氧化应激标志物水平。
与体脂增加相关的氧化应激可能导致哮喘患者类固醇敏感性受损。二甲双胍可能通过降低氧化应激来改善类固醇敏感性，提示这可能是该患者群体的一种潜在治疗方法。
