Department of Pediatrics, Albert Einstein College of Medicine, Bronx.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Chest. 2012 Apr;141(4):895-905. doi: 10.1378/chest.11-0930. Epub 2011 Oct 6.
Obesity-associated asthma has been proposed to be a distinct entity, differing in immune pathogenesis from atopic asthma. Both obesity-mediated inflammation and increase in adiposity are potential mechanistic factors that are poorly defined among children. We hypothesized that pediatric obesity-associated asthma would be characterized by T helper (Th) 1, rather than the Th2 polarization associated with atopic asthma. Moreover, we speculated that Th1 biomarkers and anthropometric measures would correlate with pulmonary function tests (PFTs) in obese asthmatic children.
We recruited 120 children, with 30 in each of the four study groups: obese asthmatic children, nonobese asthmatic children, obese nonasthmatic children, and nonobese nonasthmatic children. All children underwent pulmonary function testing. Blood was collected for measurement of serum cytokines. T-cell responses to mitogen, phorbol 12-myristate 13-acetate (PMA), or antigens tetanus toxoid or Dermatophagoides farinae were obtained by flow cytometric analysis of intracellular cytokine staining for interferon-γ (IFN-γ) (Th1) or IL-4 (Th2) within the CD4 population.
Obese asthmatic children had significantly higher Th1 responses to PMA (P < .01) and tetanus toxoid (P < .05) and lower Th2 responses to PMA (P < .05) and D farinae (P < .01) compared with nonobese asthmatic children. Th-cell patterns did not differ between obese asthmatic children and obese nonasthmatic children. Obese asthmatic children had lower FEV(1)/FVC (P < .01) and residual volume/total lung capacity ratios (P < .005) compared with the other study groups, which negatively correlated with serum interferon-inducible protein 10 and IFN-γ levels, respectively. PFTs, however, did not correlate with BMI z score or waist to hip ratio.
We found that pediatric obesity-associated asthma differed from atopic asthma and was characterized by Th1 polarization. The altered immune environment inversely correlated with PFTs in obese asthmatic children.
肥胖相关性哮喘被认为是一种独特的实体，其免疫发病机制与特应性哮喘不同。肥胖引起的炎症和脂肪量增加都是潜在的机制因素，但在儿童中尚未明确。我们假设，与特应性哮喘相关的 Th2 极化不同，儿科肥胖相关性哮喘的特点是 Th1。此外，我们推测 Th1 生物标志物和人体测量指标与肥胖哮喘儿童的肺功能测试（PFT）相关。
我们招募了 120 名儿童，每组 30 名，分为 4 个研究组：肥胖哮喘儿童、非肥胖哮喘儿童、肥胖非哮喘儿童和非肥胖非哮喘儿童。所有儿童均进行了肺功能测试。采集血液用于测量血清细胞因子。通过流式细胞术分析细胞内细胞因子染色，获得对丝裂原、佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）或破伤风类毒素或屋尘螨抗原的 T 细胞反应，以获得 IFN-γ（Th1）或白细胞介素 4（Th2）在 CD4 群体内。
与非肥胖哮喘儿童相比，肥胖哮喘儿童对 PMA（P<0.01）和破伤风类毒素（P<0.05）的 Th1 反应显著升高，而对 PMA（P<0.05）和 D 远房（P<0.01）的 Th2 反应降低。肥胖哮喘儿童与肥胖非哮喘儿童之间的 Th 细胞模式没有差异。与其他研究组相比，肥胖哮喘儿童的 FEV1/FVC（P<0.01）和残气量/总肺容量比（P<0.005）较低，这与血清干扰素诱导蛋白 10 和 IFN-γ水平分别呈负相关。然而，PFT 与 BMI z 评分或腰臀比无关。
我们发现儿科肥胖相关性哮喘与特应性哮喘不同，其特点是 Th1 极化。改变的免疫环境与肥胖哮喘儿童的 PFT 呈负相关。
