哮喘联盟

   摘要
   基本原理：胰岛素抵抗和低水平高密度脂蛋白（HDL）与包括哮喘在内的肺部疾病相关，但其内在机制尚不明确。
   目的：探索在城市青少年中，全身炎症反应是否影响代谢异常与肺功能之间的关系。
   方法：该研究纳入了42例肥胖哮喘患者、42例正常体重哮喘患者、40例肥胖非哮喘患者及42例健康对照受试者在内的168例青少年，并对他们的辅助T淋巴细胞（Th）应答、单核细胞亚群及两者与血清稳态模型评估的胰岛素抵抗（HOMA-IR）和HDL水平的关系进行了检测，同时进行了肺功能测试。采用流式细胞计数定量分析植物血凝素、瘦素、尘螨刺激后的辅助T淋巴细胞应答（Th1细胞 [CD4+IFNγ+] 和Th2细胞 [CD4+IL4+]）。同样定量分析经典单核细胞（CD14+CD16-）、定植单核细胞（CD14+CD16+）、游走单核细胞（CD14dimCD16+）以及它们的2型C-C趋化因子受体（CCR2）表达。
   测量和主要结果：对3种刺激物的刺激，Th1/Th2比值在肥胖哮喘组均高于正常体重哮喘组，并且与HOMA-IR呈正相关。经典单核细胞与植物血凝素刺激后Th1/Th2比值呈负相关（r =20.43; P = 0.01），与哮喘控制测试（ACT）得分呈正相关（β = 1.09; P = 0.04），仅在肥胖哮喘组，游走单核细胞与哮喘严重程度综合指数（CASI）得分相关（β = 1.11; P = 0.04）。HDL 与游走单核细胞呈负相关，与定植单核细胞表面CCR2表达呈正相关。在校正HDL水平后，游走单核细胞表面CCR2表达可预测残气量（RV）、残气量/肺总量比值（RV/TLC）和功能残气量（FRC），但是在校正体重指数影响后，这一关系不具有统计学意义。校正HOMA-IR因素，减弱了Th1/Th2比值与RV、FRV和深吸气量之间的联系。
   结论：在肥胖哮喘患者中，Th1极化及单核细胞活化与代谢异常相关。体重指数介导了单核细胞活化与肺功能之间的联系，而Th1极化与肺功能之间的联系由胰岛素抵抗所介导。
 

(张丽 张红萍 王刚  四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med. 2015; 191: 54–62.）

 

Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

Rastogi D, Fraser S, Oh J, Huber AM, Schulman Y, Bhagtani RH, Khan ZS, Tesfa L, Hall CB, and Macian F
Am J Respir Crit Care Med. 2015; 191: 54–62.

ABSTRACT
Rationale: Insulin resistance and low high-density lipoprotein (HDL) are associated with pulmonary morbidity, including asthma, but the underlying mechanisms are not well elucidated.
Objectives: To investigate whether systemic inflammation underlies the association of metabolic abnormalities with pulmonary function among urban adolescents.
Methods: Th-cell responses and monocyte subsets, and their association with serum homeostatic model assessment of insulin resistance (HOMA-IR) and HDL, and pulmonary function were quantified in 168 adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects. Th-cell responses (Th1 [CD41IFNg1] and Th2 [CD41IL41] cells) to stimulation with phytohemagglutinin, leptin, and dust mite,
and classical (CD141CD162), resident (CD141CD161), and patrolling (CD14dimCD161) monocytes, and their C-C chemokine receptor type-2 (CCR2) expression were quantified by flow cytometry.
Measurements and Main Results: Th1/Th2 ratio to all three stimuli was higher in obese subjects with asthma than normal-weight subjects with asthma and directly correlated with HOMA-IR. Classical monocytes inversely associated with Th1/Th2 ratio to phytohemagglutinin (r =20.43; P = 0.01) and directly with Asthma Control Test score (β = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (β = 1.11; P = 0.04) only among obese subjects with asthma. HDL was inversely associated with patrolling monocytes and directly associated with CCR2 expression on resident monocytes. CCR2 expression on patrolling monocytes predicted residual volume (RV), RV/TLC ratio, and FRC, after adjusting for HDL, but not after adjusting for body mass index. Association of Th1/Th2 ratio with RV, FRC, and inspiratory capacity was attenuated after adjusting for HOMA-IR.
Conclusions: Th1 polarization and monocyte activation among obese subjects with asthma correlates with metabolic abnormalities. Association of monocyte activation with pulmonary function is mediated by body mass index, whereas that of Th1 polarization is mediated by insulin resistance.
Keywords: obesity; asthma; metabolic dysregulation; inflammation; pulmonary function