Maclennan Carolyn, Hutchinson Paul, Holdsworth Stephen, Bardin Philip G, Freezer Nicholas J
Department of Respiratory and Sleep Medicine, Monash Medical Centre, Monash University, Melbourne, Victoria, Australia.
Pediatr Pulmonol. 2006 Jun;41(6):577-83. doi: 10.1002/ppul.20415.
Airway pathologies have been comprehensively researched in adult asthma, but in children, the extent of airway inflammation associated with episodic wheeze, often diagnosed as asthma, has not been fully characterized. It is not clear whether persistent airway inflammation is present in the absence of wheezing symptoms, and there is controversy regarding the role of age and atopy. This study assessed cellular and cytokine markers of airway inflammation in asymptomatic children with a history of episodic wheeze. Children with a history of episodic wheeze and cough (study group) and nonasthmatic patients requiring elective surgery (control group) were recruited. All subjects in the study group had a history of significant episodic wheezing (>2 episodes per year), and used only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control group). Differential cell counts of BAL and flow cytometry were performed to identify T-lymphocyte phenotypes, and intracellular cytokine profiles were measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T-cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and 21 nonasthmatic subjects without respiratory symptoms were recruited. Study and control subjects were matched for age (median age, 5 years) and demographic characteristics. Study subjects had higher IgE levels, but their measurements were still within normal range. No significant differences in BAL differential cell counts were noted, and in both groups, the majority of T-cells were CD3+ CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4, IL-5, and IL-10. The results of this study suggest that significant T-cell-driven airway inflammation is absent in mild or nonatopic, asymptomatic children of this age group who have episodic wheeze. Our findings support asthma management guidelines that do not recommend long-term treatment of this group of patients with anti-inflammatory medications.
气道病变在成人哮喘中已得到全面研究,但在儿童中,与发作性喘息(常被诊断为哮喘)相关的气道炎症程度尚未完全明确。尚不清楚在无喘息症状的情况下是否存在持续性气道炎症,而且关于年龄和特应性的作用也存在争议。本研究评估了有发作性喘息病史的无症状儿童气道炎症的细胞和细胞因子标志物。招募了有发作性喘息和咳嗽病史的儿童(研究组)以及需要择期手术的非哮喘患者(对照组)。研究组的所有受试者都有明显的发作性喘息病史(每年>2次发作),且仅按需使用β-激动剂治疗。通过支气管镜灌洗(研究组)和非支气管镜灌洗(对照组)获取支气管肺泡灌洗(BAL)样本。对BAL进行细胞分类计数并通过流式细胞术鉴定T淋巴细胞表型,在用佛波醇-12-肉豆蔻酸酯13-乙酸酯(PMA)刺激BAL液T细胞后测量细胞内细胞因子谱。招募了21名每年有2 - 12次喘息发作病史的儿童和21名无呼吸道症状的非哮喘受试者。研究组和对照组在年龄(中位年龄5岁)和人口统计学特征方面相匹配。研究对象的IgE水平较高,但仍在正常范围内。BAL细胞分类计数未发现显著差异,且两组中大多数T细胞为CD3 + CD8 +,CD4:CD8比值中位数为0.6。活化标志物HLA - DR和CD25(IL - 2受体)的T细胞表达,或PMA诱导的细胞内细胞因子IFN - γ、IL - 2、IL - 4、IL - 5和IL - 10的产生均无显著差异。本研究结果表明,在这个年龄组中,有发作性喘息的轻度或非特应性无症状儿童不存在显著的T细胞驱动的气道炎症。我们的研究结果支持哮喘管理指南,该指南不建议对这组患者长期使用抗炎药物治疗。