高中性粒细胞哮喘患者血清IgE、OCS依赖性和IL-17／22表达水平升高
2019/09/09
摘要
支气管中性粒细胞增多的哮喘相关临床特征的研究较少，导致其识别和治疗上的困难。我们旨在评估嗜中性粒细胞性哮喘的临床、功能和生物学特征，并寻找支气管中性粒细胞哮喘的预测因子。对70例轻度至重度哮喘患者的炎症表型进行了横断面研究，根据支气管固有层切片嗜酸性粒细胞/嗜中性粒细胞计数，将患者分为中性粒细胞型和非中性粒细胞型。中性粒细胞性哮喘（中性粒细胞计数临界值：47.17中性粒细胞·mm-2；范围：47.17-198.11中性粒细胞·mm-2；中位数：94.34中性粒细胞·mm-2）进一步分为高（≥94.34中性粒细胞·mm-2）或中等（≥47.17 <94.34中性粒细胞·mm-2）。吸烟10包年以上的患者效果也被评估，嗜中性粒细胞性哮喘（n=38；36例混合嗜酸性粒细胞/中性粒细胞型）较非中性粒细胞性哮喘（n=32；28例嗜酸性粒细胞型，4例寡细胞型）疾病严重程度更重，功能残气量（FRC）、ICS剂量、急性发作次数更多，FVC%和FEV1可逆性较低。与非中性粒细胞性哮喘相比，中性粒细胞性哮喘患者嗜酸性粒细胞计数相似，支气管CD8+、IL17-F+和IL-22+细胞增多，肥大细胞减少。在我们的队列中，FEV1和FVC可逆性是中性粒细胞性哮喘的独立预测因子。中性粒细胞增多患者（n＝21）的血清IgE水平、对变应原的敏感性、急性发作率升高，对口服激素（OCS）依赖性、支气管粘膜中CD4+和IL-17F+细胞数增加。排除吸烟患者后，高中性粒细胞患者的IL-17A+和IL-22+细胞也增加了。该研究提供了新的证据，证明哮喘中存在的高支气管中性粒细胞与过敏（IgE）和IL-17/IL-22细胞因子表达相关的适应性免疫反应有关。高支气管中性粒细胞增多可鉴别新的哮喘内型。支气管可逆性与支气管中性粒细胞的关系需进一步研究。
Elevated serum IgE, OCS-dependence and IL-17/22 expression in highly neutrophilic asthma.
Bullone M, Carriero V, Bertolini F, Folino A, Mannelli A, Di Stefano A, Gnemmi I, Torchio R, Ricciardolo FLM.
Abstract
Information on the clinical traits associated to bronchial neutrophilia in asthma is scant, preventing its recognition and adequate treatment. We aimed to assess the clinical, functional and biological features of neutrophilic asthma and identify possible predictors of bronchial neutrophilia. The inflammatory phenotype of 70 mild-to-severe asthmatics was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthmatics (neutrophil count cutoff: 47.17 neutrophils·mm-2; range: 47.17-198.11 neutrophils·mm-2; median: 94.34 neutrophils·mm-2) were further classified as high (≥94.34 neutrophils·mm-2) or intermediate (≥47.17 <94.34 neutrophils·mm-2). The effect of smoking ≥10 pack-years was also assessed. Neutrophilic asthmatics (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, FRC, ICS dose and exacerbations, and lower FVC% and FEV1 reversibility than non-neutrophilic asthmatics (n=32; 28 eosinophilic, 4 paucigranulocytic). Neutrophilic asthmatics had similar eosinophil counts, increased bronchial CD8+, IL17-F+, and IL-22+ cells, and decreased mast cells compared to non-neutrophilic asthmatics. FEV1 and FVC reversibility were independent predictors of bronchial neutrophilia in our cohort. High neutrophilic patients (n=21) had increased serum IgE levels, sensitivity to perennial allergens, exacerbation rate, OCS-dependence, CD4+ and IL-17F+ cells in their bronchial mucosa. Excluding smokers revealed also increased IL-17A+ and IL-22+ cells in highly neutrophilic patients. We provide new evidence linking the presence of high bronchial neutrophilia in asthma to an adaptive immune response associated with allergy (IgE) and IL-17/IL-22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.
支气管中性粒细胞增多的哮喘相关临床特征的研究较少，导致其识别和治疗上的困难。我们旨在评估嗜中性粒细胞性哮喘的临床、功能和生物学特征，并寻找支气管中性粒细胞哮喘的预测因子。对70例轻度至重度哮喘患者的炎症表型进行了横断面研究，根据支气管固有层切片嗜酸性粒细胞/嗜中性粒细胞计数，将患者分为中性粒细胞型和非中性粒细胞型。中性粒细胞性哮喘（中性粒细胞计数临界值：47.17中性粒细胞·mm-2；范围：47.17-198.11中性粒细胞·mm-2；中位数：94.34中性粒细胞·mm-2）进一步分为高（≥94.34中性粒细胞·mm-2）或中等（≥47.17 <94.34中性粒细胞·mm-2）。吸烟10包年以上的患者效果也被评估，嗜中性粒细胞性哮喘（n=38；36例混合嗜酸性粒细胞/中性粒细胞型）较非中性粒细胞性哮喘（n=32；28例嗜酸性粒细胞型，4例寡细胞型）疾病严重程度更重，功能残气量（FRC）、ICS剂量、急性发作次数更多，FVC%和FEV1可逆性较低。与非中性粒细胞性哮喘相比，中性粒细胞性哮喘患者嗜酸性粒细胞计数相似，支气管CD8+、IL17-F+和IL-22+细胞增多，肥大细胞减少。在我们的队列中，FEV1和FVC可逆性是中性粒细胞性哮喘的独立预测因子。中性粒细胞增多患者（n＝21）的血清IgE水平、对变应原的敏感性、急性发作率升高，对口服激素（OCS）依赖性、支气管粘膜中CD4+和IL-17F+细胞数增加。排除吸烟患者后，高中性粒细胞患者的IL-17A+和IL-22+细胞也增加了。该研究提供了新的证据，证明哮喘中存在的高支气管中性粒细胞与过敏（IgE）和IL-17/IL-22细胞因子表达相关的适应性免疫反应有关。高支气管中性粒细胞增多可鉴别新的哮喘内型。支气管可逆性与支气管中性粒细胞的关系需进一步研究。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Eur Respir J. 2019 Aug 22. pii: 1900068. doi: 10.1183/13993003.00068-2019.)
(Eur Respir J. 2019 Aug 22. pii: 1900068. doi: 10.1183/13993003.00068-2019.)
Elevated serum IgE, OCS-dependence and IL-17/22 expression in highly neutrophilic asthma.
Bullone M, Carriero V, Bertolini F, Folino A, Mannelli A, Di Stefano A, Gnemmi I, Torchio R, Ricciardolo FLM.
Abstract
Information on the clinical traits associated to bronchial neutrophilia in asthma is scant, preventing its recognition and adequate treatment. We aimed to assess the clinical, functional and biological features of neutrophilic asthma and identify possible predictors of bronchial neutrophilia. The inflammatory phenotype of 70 mild-to-severe asthmatics was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthmatics (neutrophil count cutoff: 47.17 neutrophils·mm-2; range: 47.17-198.11 neutrophils·mm-2; median: 94.34 neutrophils·mm-2) were further classified as high (≥94.34 neutrophils·mm-2) or intermediate (≥47.17 <94.34 neutrophils·mm-2). The effect of smoking ≥10 pack-years was also assessed. Neutrophilic asthmatics (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, FRC, ICS dose and exacerbations, and lower FVC% and FEV1 reversibility than non-neutrophilic asthmatics (n=32; 28 eosinophilic, 4 paucigranulocytic). Neutrophilic asthmatics had similar eosinophil counts, increased bronchial CD8+, IL17-F+, and IL-22+ cells, and decreased mast cells compared to non-neutrophilic asthmatics. FEV1 and FVC reversibility were independent predictors of bronchial neutrophilia in our cohort. High neutrophilic patients (n=21) had increased serum IgE levels, sensitivity to perennial allergens, exacerbation rate, OCS-dependence, CD4+ and IL-17F+ cells in their bronchial mucosa. Excluding smokers revealed also increased IL-17A+ and IL-22+ cells in highly neutrophilic patients. We provide new evidence linking the presence of high bronchial neutrophilia in asthma to an adaptive immune response associated with allergy (IgE) and IL-17/IL-22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.
上一篇：
人肺单细胞测序首次揭示健康人和哮喘患者中细胞状态差异
下一篇：
肥大细胞移位浸润气道上皮通过IL-33调节哮喘炎症
