Dept of Clinical and Biological Sciences, University of Turin, San Luigi University Hospital, Turin, Italy.
Dept of Veterinary Sciences, University of Turin, Turin, Italy.
Eur Respir J. 2019 Nov 7;54(5). doi: 10.1183/13993003.00068-2019. Print 2019 Nov.
Information on the clinical traits associated with 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 asthma patients was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthma patients (neutrophil count cut-off: 47.17 neutrophils·mm; range: 47.17-198.11 neutrophils·mm; median: 94.34 neutrophils·mm) were further classified as high (≥94.34 neutrophils·mm) or intermediate (47.17- <94.34 neutrophils·mm). The effect of smoking ≥10 pack-years was also assessed.Neutrophilic asthma patients (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, functional residual capacity, inhaled corticosteroid (ICS) dose and exacerbations, and lower forced vital capacity (FVC) % pred and forced expiratory volume in 1 s (FEV) reversibility than non-neutrophilic asthma patients (n=32; 28 eosinophilic and four paucigranulocytic). Neutrophilic asthma patients had similar eosinophil counts, increased bronchial CD8, interleukin (IL)-17-F and IL-22 cells, and decreased mast cells compared with non-neutrophilic asthma patients. FEV 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, oral corticosteroid dependence, and CD4 and IL-17F cells in their bronchial mucosa. Excluding smokers revealed 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-17/22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.
关于与哮喘支气管中性粒细胞增多相关的临床特征的信息很少，这阻碍了对其的识别和适当治疗。我们旨在评估中性粒细胞性哮喘的临床、功能和生物学特征，并确定支气管中性粒细胞增多的可能预测因素。
根据支气管固有层中的嗜酸性粒细胞/中性粒细胞计数，对 70 例轻至重度哮喘患者的炎症表型进行了横断面研究。将患者分为中性粒细胞性或非中性粒细胞性。将中性粒细胞性哮喘患者（中性粒细胞计数截止值：47.17 个中性粒细胞·mm；范围：47.17-198.11 个中性粒细胞·mm；中位数：94.34 个中性粒细胞·mm）进一步分为高（≥94.34 个中性粒细胞·mm）或中（47.17-<94.34 个中性粒细胞·mm）。还评估了吸烟≥10 包年的影响。
中性粒细胞性哮喘患者（n=38；36 例混合嗜酸性粒细胞/中性粒细胞）的疾病严重程度、功能残气量、吸入性皮质类固醇（ICS）剂量和加重程度更高，用力肺活量（FVC）%预计值和 1 秒用力呼气量（FEV）可逆性较低，而非中性粒细胞性哮喘患者（n=32；28 例嗜酸性粒细胞和 4 例少粒细胞性）。与非中性粒细胞性哮喘患者相比，中性粒细胞性哮喘患者的嗜酸性粒细胞计数相似，但支气管 CD8、白细胞介素（IL）-17-F 和 IL-22 细胞增加，而肥大细胞减少。在我们的队列中，FEV 和 FVC 可逆性是支气管中性粒细胞增多的独立预测因子。高中性粒细胞患者（n=21）血清 IgE 水平升高，对常年变应原敏感，加重率高，需要口服皮质类固醇，支气管黏膜 CD4 和 IL-17F 细胞增加。排除吸烟者后，发现高嗜中性粒细胞患者的 IL-17A 和 IL-22 细胞增加。
我们提供了新的证据，将高支气管中性粒细胞增多与与过敏（IgE）和 IL-17/22 细胞因子表达相关的适应性免疫反应联系起来。高支气管中性粒细胞增多可能区分出新的哮喘表型。需要进一步研究支气管可逆性与支气管中性粒细胞增多之间的关系。
