背景:在成人严重治疗抗性哮喘(STRA)中的研究已经证明了异质性病理生理学。儿科年龄组的研究仍然很少,很少包括支气管组织分析。
目的:我们调查了圣保罗6-18岁的STRA患者,巴西,通过表征不同的肺隔室及其与哮喘控制和肺功能的相关性。
方法:使用血液分析了13例确诊为STRA的患者的炎症谱,诱导痰,支气管肺泡灌洗,病毒和细菌筛查和支气管活检。炎症细胞,细胞因子,测试了基底膜增厚与哮喘控制测试(ACT),肺活量测定和体积描记术参数的相关性。
结果:11例患者的支气管内活检标本可用于分析。所有活检均显示嗜酸性粒细胞浸润。粘膜下(SM)嗜酸性粒细胞和中性粒细胞与肺功能较差(前BDFEV1)相关,和SM中性粒细胞与固定梗阻(后BDFEV1)相关。上皮内(IE)中性粒细胞与肺功能(前BDsGaw)呈正相关。CD8+T细胞在IE和SM层密度最高,与ACT呈正相关,与细胞因子IL1β呈负相关,IL2,IL5,IL7,IL10,IL12,IL17,GCSF,MCP-1,INF-δ,和痰上清液中的TNFα。ASM糜蛋白酶+肥大细胞密度与生活质量评分(pAQLQ)和ACT呈正相关。
结论:嗜酸性粒细胞和SM中性粒细胞与肺功能恶化相关,而IE中性粒细胞与较好的肺功能相关。最重要的是,CD8+T细胞在STRA患者的支气管活检中丰富,并显示出保护性关联,食糜酶+肥大细胞也是如此。
BACKGROUND: Studies in adult severe treatment-resistant asthma (STRA) have demonstrated heterogeneous pathophysiology. Studies in the pediatric age group are still scarce, and few include bronchial tissue analysis.
OBJECTIVE: We investigated 6-18-year-old patients diagnosed with STRA in Sao Paulo, Brazil, by characterizing the different lung compartments and their correlations with asthma control and lung function.
METHODS: Inflammatory profiles of 13 patients with a confirmed diagnosis of STRA were analyzed using blood, induced sputum, bronchoalveolar lavage, viral and bacterial screens and endobronchial biopsy. Inflammatory cells, cytokines, and basement membrane thickening were tested for correlations with the asthma control test (ACT) and spirometry and plethysmography parameters.
RESULTS: Endobronchial biopsy specimens from 11 patients were viable for analysis. All biopsies showed eosinophilic infiltration. Submucosal (SM) eosinophils and neutrophils were correlated with worse lung function (pre-BD FEV1), and SM neutrophils were correlated with fixed obstruction (post-BD FEV1). Intraepithelial (IE) neutrophils were positively correlated with lung function (pre-BD sGaw). CD8 + T cells had the highest density in the IE and SM layers and were positively correlated with ACT and negatively correlated with the cytokines IL1β, IL2, IL5, IL7, IL10, IL12, IL17, GCSF, MCP-1, INF-δ, and TNFα in sputum supernatant. The ASM chymase + mast cell density correlated positively with quality-of-life score (pAQLQ) and ACT.
CONCLUSIONS: Eosinophils and SM neutrophils correlated with worse lung function, while IE neutrophils correlated with better lung function. Most importantly, CD8 + T cells were abundant in bronchial biopsies of STRA patients and showed protective associations, as did chymase + mast cells.