高度中性粒细胞性哮喘患者血清IgE升高，OCS依赖性和IL-17/22表达升高
2020/02/11
摘要
有关支气管嗜中性粒细胞性哮喘的临床特征的资料很少，这不利于对其的识别和充分的治疗。我们的目的是评估嗜中性粒细胞哮喘的临床、功能和生物学特征，并确定可能的支气管嗜中性粒细胞增多症的预测因子。根据70例轻度至重度哮喘患者的支气管固有层嗜酸性/中性粒细胞计数，对其炎症表型进行横断面研究。嗜中性哮喘患者(中性粒细胞计数截断值：: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(≥47.17 <94.34中性粒细胞·mm-2)。吸烟≥10累计吸烟量的效应也进行了评估。中性粒细胞哮喘患者(n = 38; 36例嗜酸性/中性粒细胞性哮喘混合)，哮喘患者的病情严重程度、FRC、ICS剂量及病情加重程度均高于非嗜中性哮喘患者(n=32;28例嗜酸性粒细胞型，4例粒细胞缺乏型)，且FVC%和FEV1可逆性均低于非嗜中性哮喘患者。嗜中性粒细胞性哮喘患者与非嗜中性粒细胞性哮喘患者相比，嗜酸性粒细胞计数相似，支气管CD8+、IL17-F+、IL-22+细胞增多，肥大细胞减少。FEV1和FVC的可逆性是本研究中支气管嗜中性粒细胞增多的独立预测因子。高嗜中性粒细胞患者(n=21)在支气管粘膜中增加了血清IgE水平，对常年变应原敏感性，加重率，ocs依赖性，CD4+和IL-17F+细胞。除吸烟者外，高中性粒细胞患者的IL-17A+和IL-22+细胞也增加。我们提供了新的证据，表明哮喘中支气管嗜中性粒细胞增多对适应性免疫反应与过敏(IgE)和IL-17/IL-22细胞因子表达有关。支气管嗜中性粒细胞增多可鉴别一种新的哮喘内型。支气管可逆性与支气管嗜中性粒细胞之间的关系有待进一步研究。
Elevated serum IgE, OCS-dependence and IL-17/22 expression in highly neutrophilic asthma.
Bullone M.et al. Eur Respir J. 2019 Aug 22.
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.
有关支气管嗜中性粒细胞性哮喘的临床特征的资料很少，这不利于对其的识别和充分的治疗。我们的目的是评估嗜中性粒细胞哮喘的临床、功能和生物学特征，并确定可能的支气管嗜中性粒细胞增多症的预测因子。根据70例轻度至重度哮喘患者的支气管固有层嗜酸性/中性粒细胞计数，对其炎症表型进行横断面研究。嗜中性哮喘患者(中性粒细胞计数截断值：: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(≥47.17 <94.34中性粒细胞·mm-2)。吸烟≥10累计吸烟量的效应也进行了评估。中性粒细胞哮喘患者(n = 38; 36例嗜酸性/中性粒细胞性哮喘混合)，哮喘患者的病情严重程度、FRC、ICS剂量及病情加重程度均高于非嗜中性哮喘患者(n=32;28例嗜酸性粒细胞型，4例粒细胞缺乏型)，且FVC%和FEV1可逆性均低于非嗜中性哮喘患者。嗜中性粒细胞性哮喘患者与非嗜中性粒细胞性哮喘患者相比，嗜酸性粒细胞计数相似，支气管CD8+、IL17-F+、IL-22+细胞增多，肥大细胞减少。FEV1和FVC的可逆性是本研究中支气管嗜中性粒细胞增多的独立预测因子。高嗜中性粒细胞患者(n=21)在支气管粘膜中增加了血清IgE水平，对常年变应原敏感性，加重率，ocs依赖性，CD4+和IL-17F+细胞。除吸烟者外，高中性粒细胞患者的IL-17A+和IL-22+细胞也增加。我们提供了新的证据，表明哮喘中支气管嗜中性粒细胞增多对适应性免疫反应与过敏(IgE)和IL-17/IL-22细胞因子表达有关。支气管嗜中性粒细胞增多可鉴别一种新的哮喘内型。支气管可逆性与支气管嗜中性粒细胞之间的关系有待进一步研究。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Bullone M.et al. Eur Respir J. 2019 Aug 22.）
（Bullone M.et al. Eur Respir J. 2019 Aug 22.）
Elevated serum IgE, OCS-dependence and IL-17/22 expression in highly neutrophilic asthma.
Bullone M.et al. Eur Respir J. 2019 Aug 22.
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.
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临床中利用电子鼻分析呼出气体以评估难控制哮喘症状
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呼出的挥发性有机化合物能够区分嗜中性粒细胞和嗜酸性哮喘
