Zhang Xin, Zheng Jing, Zhang Li, Liu Ying, Chen Gai Ping, Zhang Hong Ping, Wang Lei, Kang De Ying, Wood Lisa G, Wang Gang
Allergy Asthma Proc. 2018 Jan 2;39(1):43-50. doi: 10.2500/aap.2018.39.4096.
Obesity negatively impacts asthma control, but the inflammatory mechanisms are poorly understood.
To explore which systemic inflammatory mediators mediate the effects of obesity on asthma control.
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/m2, overweight was defined as BMI between 25 to 29.9 kg/m2, and lean weight was defined as BMI < 25 kg/m2. 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.
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 cm2; 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.
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.
肥胖对哮喘控制有负面影响，但其炎症机制尚不清楚。
探讨哪些全身炎症介质介导肥胖对哮喘控制的影响。
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）≥30kg/m²，超重定义为BMI在25至29.9kg/m²之间，瘦体重定义为BMI<25kg/m²。通过生物电阻抗分析身体成分，包括脂肪量（FM）、内脏脂肪面积（VFA）和体脂百分比（PBF）。采用酶联免疫吸附测定法（ELISA）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、CCL22、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。
瘦（n=52）、超重（n=37）和肥胖（n=19）受试者的FM（12.73±3.95对18.59±2.95对27.82±5.17kg；p<0.0001）、VFA（65.99±23.17对93.96±10.28对123.10±18.34cm²；p<0.0001）、PBF（23.86±7.46对30.74±5.08对36.21±6.28%；p=0.0003）和ACQ-6值（0.83[0，1.17]对1.15[0.50，1.75]对1.33[0.83，1.83]分；p=0.002）存在差异。与瘦或超重受试者相比，肥胖组血清瘦素、IL-5、IL-13、IL-17、CCL17、CRP和IFN-γ水平显著升高（均p<0.05）。中介分析发现，以BMI评估的肥胖对ACQ-6的影响通过IL-13和CCL17显著介导。此外，IL-13和CCL17介导身体成分（FM、VFA和PBF）对ACQ-6的影响。以身体成分而非BMI评估的肥胖对ACQ-6的影响由瘦素介导。
我们的中介分析证实，瘦素、CCL17、IL-4和IL-13等全身炎症生物标志物介导了肥胖对哮喘控制的影响。这值得在未来对这种独特的哮喘表型进行前瞻性探索。
