Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Respirology. 2018 Nov;23(11):1023-1031. doi: 10.1111/resp.13312. Epub 2018 Apr 26.
Inflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers for clinical response to inhaled corticosteroids (ICS).
In total, 114 steroid-naïve COPD patients of the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study using ICS or placebo during 30-month follow-up were included. Cell counts in blood, sputum, biopsies and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV ), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated.
Cross-sectional analyses at baseline showed that higher blood eosinophils were significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV changes. Higher baseline biopsy eosinophils were associated with an increase in symptoms during 6- and 30-month ICS treatment. In addition, higher biopsy neutrophils were associated with a more marked reduction in hyperinflation during 6-month ICS treatment compared with placebo.
Our findings indicate that blood eosinophils reflect eosinophils in other compartments, in contrast to neutrophils, in ICS-naïve COPD patients. Both baseline eosinophils and neutrophils do not predict ICS-induced lung function changes over a period of 6-30 months. The associations of biopsy eosinophils with worsening respiratory symptoms and biopsy neutrophils with improvement in hyperinflation during ICS treatment deserve further investigation.
在 COPD 患者中，炎症存在不同程度和组成。本研究调查了血液、痰、气道壁活检和支气管肺泡灌洗（BAL）中嗜酸性粒细胞和中性粒细胞之间的关联及其作为吸入皮质类固醇（ICS）临床反应生物标志物的潜在用途。
共纳入 114 名来自格罗宁根莱顿大学皮质类固醇在阻塞性肺病（GLUCOLD）研究的ICS 或安慰剂治疗 30 个月的初治 COPD 患者。在基线时评估血液、痰、活检和 BAL 中的细胞计数。此外，在基线、6 个月和 30 个月时评估 1 秒用力呼气量（FEV ）、残气量/总肺容量（过度充气）和临床 COPD 问卷。
基线时的横断面分析显示，较高的血液嗜酸性粒细胞与痰、活检和 BAL 中的嗜酸性粒细胞计数显著相关。然而，血液中性粒细胞与其他部位的中性粒细胞计数无显著相关性。无论在哪个部位测量，基线嗜酸性粒细胞和中性粒细胞均不能预测 FEV 的纵向变化。较高的基线活检嗜酸性粒细胞与 6 个月和 30 个月 ICS 治疗期间症状的增加相关。此外，与安慰剂相比，较高的基线活检中性粒细胞与 6 个月 ICS 治疗期间过度充气的更显著减少相关。
我们的研究结果表明，与中性粒细胞相比，ICS 初治 COPD 患者血液中的嗜酸性粒细胞反映了其他部位的嗜酸性粒细胞。基线嗜酸性粒细胞和中性粒细胞均不能预测 6-30 个月期间 ICS 诱导的肺功能变化。活检嗜酸性粒细胞与呼吸症状恶化的关联以及活检中性粒细胞与 ICS 治疗期间过度充气改善的关联值得进一步研究。
