减肥和维生素D改善肥胖哮喘患者对皮质类固醇的低反应性
2022/09/20
摘要
背景和目的：肥胖通过未知机制对吸入皮质类固醇的哮喘反应产生负面影响。目的：证明肥胖哮喘患者对吸入皮质类固醇的不良反应与皮质类固醇抗炎活性受损和维生素D缺乏有关，两者均因体重减轻而改善。
方法：研究入组了23名肥胖性哮喘患者（OA）[18名女性；中位年龄（四分位数范围）56（51-59）岁]，14名非肥胖性哮喘（NOA）[11名女性；53（43-60）岁]，15名肥胖（O）[13名女性；47（45-60）年]和19名健康对照组（HC）[14名女性；43（34-56）岁]。10名OA和11名O患者在基线（V1）和减肥手术后6个月（V2）进行评估。皮质类固醇反应通过地塞米松抑制外周血单个核细胞（PBMC）增殖来测定。在V1和V2时测量肺功能、血清瘦素、脂联素和维生素D水平。
结果：我们发现O型和OA患者的PBMC对地塞米松的反应与NOA和HC受试者相比降低，这与脂联素/瘦素比值和维生素D水平呈负相关。减肥手术改善了O型和OA患者的皮质类固醇反应，并使脂联素/瘦素比率和维生素D水平正常化。PBMC暴露于维生素D可增强皮质类固醇的抗增殖作用。地塞米松和维生素D在O和OA患者中诱导类似的MKP-1表达。
结论：与NOA和HC受试者相比，我们发现O和OA患者PBMC对地塞米松的反应降低，这与脂联素/瘦素比率和维生素D水平呈负相关。减肥手术改善了O型和OA患者的皮质类固醇反应，并使脂联素/瘦素比率和维生素D水平正常化。PBMC暴露于维生素D可增强皮质类固醇的抗增殖作用。地塞米松和维生素D在O和OA患者中诱导类似的MKP-1表达。
Weight loss and vitamin D improve hyporesponsiveness to corticosteroids in obese asthma
M Bantulà, V Tubita, J Roca-Ferrer, J Mullol, A Valero, I Bobolea, M Pascal, A de Hollanda, J Vidal, C Picado, E Arismendi
Abstract
Background and objective: Obesity negatively impacts on asthma response to inhaled corticosteroids by unknown mechanisms. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma is associated with an impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both improved by weight loss.
Methods: 23 obese asthmatics (OA) [18 females; median age (interquartile range) 56 (51-59) years], 14 non-obese asthmatics (NOA) [11 females; 53 (43-60) years], 15 obese (O) [13 females; 47 (45-60) years], and 19 healthy controls (HC) [14 females; 43 (34-56) years] were enrolled. 10 OA and 11 O patients were evaluated at baseline (V1) and six months after (V2) bariatric surgery. Corticosteroid response was measured by dexamethasone inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function, serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2.
Results: We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the diponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients.
Conclusion: We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients.
背景和目的：肥胖通过未知机制对吸入皮质类固醇的哮喘反应产生负面影响。目的：证明肥胖哮喘患者对吸入皮质类固醇的不良反应与皮质类固醇抗炎活性受损和维生素D缺乏有关，两者均因体重减轻而改善。
方法：研究入组了23名肥胖性哮喘患者（OA）[18名女性；中位年龄（四分位数范围）56（51-59）岁]，14名非肥胖性哮喘（NOA）[11名女性；53（43-60）岁]，15名肥胖（O）[13名女性；47（45-60）年]和19名健康对照组（HC）[14名女性；43（34-56）岁]。10名OA和11名O患者在基线（V1）和减肥手术后6个月（V2）进行评估。皮质类固醇反应通过地塞米松抑制外周血单个核细胞（PBMC）增殖来测定。在V1和V2时测量肺功能、血清瘦素、脂联素和维生素D水平。
结果：我们发现O型和OA患者的PBMC对地塞米松的反应与NOA和HC受试者相比降低，这与脂联素/瘦素比值和维生素D水平呈负相关。减肥手术改善了O型和OA患者的皮质类固醇反应，并使脂联素/瘦素比率和维生素D水平正常化。PBMC暴露于维生素D可增强皮质类固醇的抗增殖作用。地塞米松和维生素D在O和OA患者中诱导类似的MKP-1表达。
结论：与NOA和HC受试者相比，我们发现O和OA患者PBMC对地塞米松的反应降低，这与脂联素/瘦素比率和维生素D水平呈负相关。减肥手术改善了O型和OA患者的皮质类固醇反应，并使脂联素/瘦素比率和维生素D水平正常化。PBMC暴露于维生素D可增强皮质类固醇的抗增殖作用。地塞米松和维生素D在O和OA患者中诱导类似的MKP-1表达。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Investig Allergol Clin Immunol. 2022 Sep 8;0. doi: 10.18176/jiaci.0861.)
(J Investig Allergol Clin Immunol. 2022 Sep 8;0. doi: 10.18176/jiaci.0861.)
Weight loss and vitamin D improve hyporesponsiveness to corticosteroids in obese asthma
M Bantulà, V Tubita, J Roca-Ferrer, J Mullol, A Valero, I Bobolea, M Pascal, A de Hollanda, J Vidal, C Picado, E Arismendi
Abstract
Background and objective: Obesity negatively impacts on asthma response to inhaled corticosteroids by unknown mechanisms. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma is associated with an impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both improved by weight loss.
Methods: 23 obese asthmatics (OA) [18 females; median age (interquartile range) 56 (51-59) years], 14 non-obese asthmatics (NOA) [11 females; 53 (43-60) years], 15 obese (O) [13 females; 47 (45-60) years], and 19 healthy controls (HC) [14 females; 43 (34-56) years] were enrolled. 10 OA and 11 O patients were evaluated at baseline (V1) and six months after (V2) bariatric surgery. Corticosteroid response was measured by dexamethasone inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function, serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2.
Results: We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the diponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients.
Conclusion: We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients.
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