Systemic inflammation mediates the detrimental effects of obesity on asthma control
Systemic inflammation mediates the detrimental effects of obesity on asthma control
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全身炎症介导肥胖对哮喘控制的有害影响
DOI：
10.2500/aap.2018.39.4096
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Wang, Gang
中科院分区：
文献类型：
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作者：
Zhang, Xin;Zheng, Jing;Wang, Gang
背景资料：肥胖对哮喘控制有负面影响，但炎症机制知之甚少。目的：探讨哪些全身炎症介质介导肥胖对哮喘控制的影响。方法：对108例稳定期哮喘患者进行临床特征评估，包括使用哮喘控制问卷（ACQ）-6。肥胖定义为体重指数（BMI）≥ 30 kg/m2，超重定义为BMI在25至29.9 kg/m2之间，瘦体重定义为BMI < 25 kg/m2。采用生物阻抗法分析了体成分，包括脂肪量（FM）、内脏脂肪面积（VFA）和体脂百分比（PBF）。采用ELISA法检测血清白细胞介素（IL）4、IL-5、IL-8、IL-13、IL-17、趋化因子（C-C基序）配体（CCL）17、CCL 22、瘦素、脂联素、C反应蛋白（CRP）和干扰素（IFN）γ。根据Baron和Kenny程序拟合线性回归模型进行中介分析。（12.73 ± 3.95 vs 18.59 ± 2.95 vs 27.82 ± 5.17 kg; p = 0.0001），VFA（65.99 ± 23.17 vs 93.96 ± 10.28 vs 123.10 ± 18.34 cm（2）; p = 0.0001），PBF（23.86 +/- 7.46 vs 30.74 +/- 5.08 vs 36.21 +/-6.28%; p = 0.0003）和ACQ-6值（0.83 [0，1.17]）与1.15 [0.50，1.75]与1.33 [0.83，1.83]评分; p = 0.002）在瘦（n = 52）、超重（n = 37）和肥胖（n = 19）受试者中存在差异。肥胖组的瘦素、IL-5、IL-13、IL-17、CCL 17、CRP和IFN-γ的血清水平与瘦或超重的受试者相比显著升高（所有p = 0.05）。中介分析发现，肥胖对ACQ-6的影响（通过BMI评估）通过IL-13和CCL 17显著介导。此外，IL-13和CCL 17介导了身体成分（FM、VFA和PBF）对ACQ-6的影响。肥胖的影响评估身体成分，但不是通过使用BMI，ACQ-6介导的leptin.Conclusion：我们的调解分析证实，全身炎症生物标志物，如瘦素，CCL 17，IL-4，IL-13，介导的肥胖对哮喘控制的影响。这保证了未来在这种独特的哮喘表型中的前瞻性探索。
Background: Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood.Objective: To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control.Methods: The subjects with stable asthma (n = 108) underwent assessment of clinical characteristics, which included using The Asthma Control Questionnaire (ACQ)-6. Obesity was defined as a body mass index (BMI) of >= 30 kg/m(2), overweight was defined as BMI between 25 to 29.9 kg/m(2), and lean weight was defined as BMI < 25 kg/m(2). Body composition, including fat mass (FM), visceral fat area (VFA), and percentage body fat (PBF) was analyzed by bioimpedance. Serum interleukin (IL) 4, IL-5, IL-8, IL-13, IL-17, chemokine (C-C motif) ligand (CCL) 17, CCL22, leptin, adiponectin, C-reactive protein (CRP), and interferon (IFN) gamma were measured by using ELISA. Linear regression models were fitted according to the Baron and Kenny procedures for mediation analysis.Results: FM (12.73 +/- 3.95 versus 18.59 +/- 2.95 versus 27.82 +/- 5.17 kg; p = 0.0001), VFA (65.99 +/- 23.17 versus 93.96 +/- 10.28 versus 123.10 +/- 18.34 cm(2); p = 0.0001), PBF (23.86 +/- 7.46 versus 30.74 +/- 5.08 versus 36.21 +/- 6.28 %; p = 0.0003) and ACQ-6 values (0.83 [0, 1.17]) versus 1.15 [0.50, 1.75] versus 1.33 [0.83, 1.83] score; p = 0.002) were different among lean (n = 52), overweight (n = 37), and obese (n = 19) subjects. Serum levels of leptin, IL-5, IL-13, IL-17, CCL17, CRP, and IFN-gamma in the obese group were significantly elevated compared with the subjects who were lean or overweight (all p = 0.05). The mediation analyses found that the effect of obesity, assessed by BMI, on ACQ-6 was significantly mediated through IL-13 and CCL17. Furthermore, IL-13 and CCL17 mediated the effects of body composition (FM, VFA and PBF) on ACQ-6. The effects of obesity assessed by body composition, but not by using BMI, on ACQ-6 were mediated by leptin.Conclusion: Our mediation analysis confirmed that systemic inflammation biomarkers, such as leptin, CCL17, IL-4, and IL-13, mediated the effects of obesity on asthma control. This warrants prospective exploration in this distinct asthma phenotype in the future.