Ishikawa Nobuhisa, Hattori Noboru, Kohno Nobuoki, Kobayashi Akihiro, Hayamizu Tomoyuki, Johnson Malcolm
Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan.
Department of Molecular and Internal Medicine, Hiroshima University, Hiroshima, Japan.
Int J Chron Obstruct Pulmon Dis. 2015 Jan 23;10:185-92. doi: 10.2147/COPD.S74557. eCollection 2015.
To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups.
This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures.
The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum.
These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan.
通过测量日本慢性阻塞性肺疾病(COPD)患者及相关对照组的气道和全身炎症生物标志物,评估炎症在COPD中的重要性。
这是日本COPD患者中的首例此类研究。这是一项非治疗性研究,100名参与者被纳入三个组之一:非吸烟对照组、现吸烟者或既往吸烟者对照组以及COPD患者。所有参与者均接受标准肺功能评估,并提供痰液和血液样本,使用标准程序测量其中炎症细胞数量和生物标志物浓度。
COPD患者痰液和血液中炎症细胞及生物标志物水平的总体趋势与西方研究中的既往报道一致。与非COPD对照参与者相比,日本COPD患者痰液中的中性粒细胞、白细胞介素8(IL-8)、表面活性蛋白D(SP-D)和克雷伯氏肺表面活性蛋白6(KL-6)水平升高,血清和血浆纤维蛋白原中的克拉拉细胞16(CC-16)、高敏C反应蛋白(hs-CRP)和KL-6水平升高。在痰液中,总细胞计数与基质金属蛋白酶9(MMP-9;P<0.001)、中性粒细胞与MMP-9(P<0.001)、巨噬细胞与KL-6(P<0.01)、总细胞计数与IL-8(P<0.05)、中性粒细胞与IL-8(P<0.05)以及巨噬细胞与MMP-9(P<0.05)之间存在显著相关性。痰液中的一些炎症细胞与血清中的生物标志物之间也观察到显著相关性,其中血清CC-16与痰液中的总细胞计数(P<0.005)和中性粒细胞(P<0.005)之间的相关性最为显著。
这些结果首次提供了证据,表明日本患者的COPD是一种多成分疾病,除气道阻塞外,还涉及气道和全身炎症。因此,抗炎治疗干预可能会给日本COPD疾病管理带来额外益处。