Heterogeneity of airway inflammation in persistent asthma - Evidence of neutrophilic inflammation and increased sputum interleukin-8
Heterogeneity of airway inflammation in persistent asthma - Evidence of neutrophilic inflammation and increased sputum interleukin-8
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DOI：
10.1378/chest.119.5.1329
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发表时间：
2001-05-01
期刊：
影响因子：
9.6
通讯作者：
Saltos, N
中科院分区：
文献类型：
--
作者：
Gibson, PG;Simpson, JL;Saltos, N
研究目的：目的：探讨持续性哮喘患者气道炎症的特点及嗜酸性粒细胞性炎症在非嗜酸性粒细胞性持续性哮喘中的作用。方法：对56例持续性哮喘的非吸烟成年患者和8例健康对照者进行高渗盐水激发和诱导痰试验。选择痰液部分用二硫苏糖醇分散，并测定总细胞计数、细胞分类、上清液嗜酸性粒细胞阳离子蛋白（ECP）、髓过氧化物酶和白细胞介素（IL-8）。41%的受试者发生典型的嗜酸性粒细胞性炎症，而其余受试者表现为非嗜酸性粒细胞性哮喘（59%）。与嗜酸性粒细胞哮喘受试者（14%，41 x 10 6/mL）和对照受试者（34%，49 x 10 6/mL; p = 0.0001）相比，非嗜酸性粒细胞哮喘受试者（64%，283 x 10 6/mL）的中性粒细胞百分比和中性粒细胞绝对计数均升高。髓过氧化物酶在非嗜酸性粒细胞和非嗜酸性粒细胞中均升高，（280 ng/mL）和嗜酸性粒细胞组（254 ng/mL）与对照受试者相比（82 ng/mL; p = 0.002），非嗜酸性粒细胞性哮喘受试者的痰液IL-8水平最高与嗜酸性粒细胞性哮喘（9.6 ng/mL）和对照受试者（3.5 ng/mL; p = 0.0001）相比，嗜中性粒细胞与IL-8水平相关（r = 0.72）。嗜酸性粒细胞性哮喘受试者的ECP最高（2，685 ng/mL），与非嗜酸性粒细胞性哮喘（1，081 ng/mL）和对照受试者（110 ng/mL; p = 0.0001）相比，结论：诱导痰分析在持续性哮喘中识别出两种不同的炎症模式。最常见的模式是非嗜酸性粒细胞，与嗜中性粒细胞流入和活化有关，这可能是由IL-8分泌介导的。在持续性哮喘中存在气道炎症的异质性，这表明不同的机制并可能影响治疗反应。
Study objectives: To identify the characteristics of airway inflammation in persistent asthma and to examine the role of neutrophilic inflammation in noneosinophilic persistent asthma.Methods: Nonsmoking adults (n = 56) with persistent asthma and healthy control subjects (n = 8) underwent hypertonic saline solution challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for total cell count, cellular differential, supernatant eosinophil cationic protein (ECP), myeloperoxidase, and interleukin (IL)-8.Results: We identified two distinct inflammatory patterns. Typical eosinophilic inflammation occurred in 41% of subjects, whereas the remainder exhibited noneosinophilic asthma (59%). Both neutrophil percentage and absolute neutrophil counts were increased in subjects with noneosinophilic asthma (64%, 283 x 10(6)/mL) compared to eosinophilic asthma (14%, 41 x 10(6)/mL) and control subjects (34%, 49 x 10(6)/mL; p = 0.0001). Myeloperoxidase was elevated in both noneosinophilic (280 ng/mL) and eosinophilic groups (254 ng/mL) compared with control subjects (82 ng/mL; p = 0.002), Sputum IL-8 levels were highest in subjects with noneosinophilic asthma (45 ng/mL) compared to eosinophilic asthma (9.6 ng/mL) and control subjects (3.5 ng/mL; p = 0.0001), Neutrophils correlated with IL-8 levels (r = 0.72). ECP was highest in subjects with eosinophilic asthma (2,685 ng/mL) compared with noneosinophilic asthma (1,081 ng/mL) and control subjects (110 ng/mL; p = 0.0001),Conclusion: Induced-sputum analysis in persistent asthma identifies two different inflammatory patterns. The most common pattern is noneosinophilic, associated with a neutrophil influx and activation, which may be mediated by IL-8 secretion. There is heterogeneity of airway inflammation in persistent asthma, which indicates differing mechanisms and may impact on treatment responses.