Alam Rafeul, Good James, Rollins Donald, Verma Mukesh, Chu HongWei, Pham Tuyet-Hang, Martin Richard J
Department of Medicine, National Jewish Health, Denver, Colo.
Department of Medicine, National Jewish Health, Denver, Colo.
J Allergy Clin Immunol. 2017 Oct;140(4):1004-1014.e13. doi: 10.1016/j.jaci.2016.12.963. Epub 2017 Feb 3.
Despite progress in the diagnosis and management of asthma, many patients have poorly controlled or refractory asthma (RA). The mechanism of this RA is not well understood.
We sought to explore the relationship between neutrophils and other biomarkers of RA.
Sixty patients with RA, 30 patients with nonrefractory asthma (NRA), and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest computed tomography, and bronchoscopy with bronchoalveolar lavage (BAL). We analyzed BAL fluid and serum for a total of 244 biomolecules using a multiplex assay and correlated them with clinical and other laboratory parameters.
RA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL fluid neutrophil and lymphocyte counts but not eosinophil counts. BAL fluid neutrophil counts negatively and positively correlated with forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL fluid and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL fluid neutrophil counts. BAL fluid from 40% of patients with RA was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in levels of select biomarkers of inflammation in the serum, suggesting the presence of systemic inflammation.
RA was associated with increased numbers of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of patients with RA, which likely contributed to neutrophilic inflammation. A subgroup of patients with noninfected neutrophilic RA was associated with systemic inflammation.
尽管哮喘的诊断和管理取得了进展，但许多患者的哮喘控制不佳或为难治性哮喘（RA）。这种RA的机制尚未完全明确。
我们试图探讨中性粒细胞与RA其他生物标志物之间的关系。
纳入60例RA患者、30例非难治性哮喘（NRA）患者和20名健康受试者。我们对这些研究对象进行了全面的特征分析，包括实验室检查和肺功能研究、胸部计算机断层扫描以及支气管镜检查和支气管肺泡灌洗（BAL）。我们使用多重分析方法分析了BAL液和血清中的总共244种生物分子，并将它们与临床和其他实验室参数相关联。
RA在肺功能指标、支气管基底膜厚度以及BAL液中性粒细胞和淋巴细胞计数方面与NRA有显著差异，但嗜酸性粒细胞计数无差异。BAL液中性粒细胞计数分别与用力肺活量和年龄呈负相关和正相关。在研究的244种生物分子中，BAL液中的52种和血清中的14种生物分子在研究组之间有显著差异。这52种分子中的13种与BAL液中性粒细胞计数相关。40%的RA患者的BAL液中有一种致病微生物呈阳性。感染阴性的嗜中性粒细胞性RA与血清中某些炎症生物标志物水平的升高有关，提示存在全身炎症。
RA与气道中中性粒细胞和嗜中性粒细胞生物分子数量增加有关。40%的RA患者存在亚临床感染，这可能导致嗜中性粒细胞炎症。非感染性嗜中性粒细胞性RA患者亚组与全身炎症有关。
