Laboratory of Cellular and Molecular Immunology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Neuroimmunomodulation. 2011;18(2):98-102. doi: 10.1159/000320343. Epub 2010 Oct 22.
Persistent asthma in children is a chronic inflammatory disease and glucocorticoids (GCs) are currently recognized as the mainstay of therapy. Clinical and in vitro steroid resistance has been demonstrated in severe asthma. However, GC insensitivity has not been studied in children with controlled persistent asthma.
To analyze peripheral blood mononuclear cell (PBMC) sensitivity to GC in children (6-15 years) with persistent asthma and healthy controls.
Children with persistent asthma were selected and lung function and skin-prick tests were performed in all studied asthmatic children. PBMCs were isolated and cultured in vitro to assess mitogen-induced proliferation and cellular sensitivity to dexamethasone.
Fifty-seven children with persistent and controlled asthma (mean age 10 years) were recruited and divided into 3 groups (severe, moderate and mild), and compared to healthy children (n = 18). Children with asthma, regardless of the severity of disease, presented similar sensitivity to GCs when compared to healthy children. Patients with mild asthma showed significantly less sensitivity to dexamethasone and children with severe asthma had similar sensitivity to dexamethasone when compared to controls.
In vitro insensitivity to GCs was not demonstrated in children with controlled persistent asthma, even in those with severe disease. Our findings suggest that resistance to GCs in older patients with severe asthma might be an acquired process. However, future longitudinal studies are necessary to confirm this hypothesis.
儿童持续性哮喘是一种慢性炎症性疾病，目前糖皮质激素（GCs）被认为是主要的治疗方法。在严重哮喘中已经证明了临床和体外类固醇耐药性。然而，尚未研究过控制良好的持续性哮喘儿童的 GC 不敏感性。
分析儿童（6-15 岁）持续性哮喘患者外周血单个核细胞（PBMC）对 GC 的敏感性。
选择持续性哮喘患儿，并对所有研究性哮喘患儿进行肺功能和皮肤点刺试验。分离 PBMC 并在体外培养以评估有丝分裂原诱导的增殖和细胞对地塞米松的敏感性。
招募了 57 名患有持续性和控制良好的哮喘的儿童（平均年龄 10 岁），并将他们分为 3 组（严重、中度和轻度），并与健康儿童（n=18）进行比较。无论疾病严重程度如何，哮喘儿童对 GCs 的敏感性与健康儿童相似。轻度哮喘患儿对地塞米松的敏感性明显降低，而重度哮喘患儿对地塞米松的敏感性与对照组相似。
在控制良好的持续性哮喘儿童中，未显示体外对 GCs 的不敏感性，即使在患有严重疾病的儿童中也是如此。我们的发现表明，严重哮喘老年患者对 GCs 的耐药性可能是一个获得性过程。然而，需要进一步的纵向研究来证实这一假设。
