Caram Laura Miranda de Oliveira, Ferrari R, Nogueira D L, Oliveira Mrm, Francisqueti F V, Tanni S E, Corrêa C R, Godoy I
Department of Internal Medicine.
Department of Pathology, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu Campus, Botucatu-São Paulo, Brazil.
Int J Chron Obstruct Pulmon Dis. 2017 Jul 7;12:2015-2021. doi: 10.2147/COPD.S138558. eCollection 2017.
Oxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients.
We evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6, TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were measured in serum.
There were higher CRP and AGEs concentrations in smokers and in patients with COPD (<0.001 and =0.01, respectively) compared to controls, without statistical difference between smokers and patients with COPD. Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups. TNFR2 was significantly higher in patients with COPD than in smokers (=0.004) and controls (=0.004), and the presence of COPD (=0.02) and CRP (=0.001) showed a positive association with TNFR2. Positive associations for smoking (=0.04), CRP (=0.03), and IL-6 (=0.03) with AGEs were also found. The interaction variable (smoking × COPD) showed a positive association with IL-6.
Our data suggest that TNFR2 may be a possible marker of COPD in asymptomatic smokers and ex-smokers. Although smokers and patients with early COPD presented other increased systemic inflammation markers (eg, CRP) and oxidative stress (measured by AGEs), they did not differentiate smokers from COPD.
吸烟者和慢性阻塞性肺疾病(COPD)患者的氧化应激和全身炎症水平较高;然而,尚未发现有助于区分吸烟者和COPD患者的标志物。我们假设肿瘤坏死因子-α受体(TNFR)和晚期糖基化终产物受体的可溶性形式(sRAGE)可作为无症状患者COPD的指标。
我们评估了32名吸烟者(吸烟史>10包年)、32名轻度/中度COPD患者(吸烟者和已戒烟者)以及32名从不吸烟者。测定血清中C反应蛋白(CRP)、白细胞介素(IL)-6、TNFR1和TNFR2、晚期糖基化终产物(AGEs)以及sRAGE的浓度。
与对照组相比,吸烟者和COPD患者的CRP和AGEs浓度更高(分别<0.001和=0.01),吸烟者和COPD患者之间无统计学差异。研究组之间sRAGE、IL-6和TNFR1的浓度无差异。COPD患者的TNFR2显著高于吸烟者(=0.004)和对照组(=0.004),COPD的存在(=0.02)和CRP(=0.001)与TNFR2呈正相关。还发现吸烟(=0.04)、CRP(=0.03)和IL-6(=0.03)与AGEs呈正相关。交互变量(吸烟×COPD)与IL-6呈正相关。
我们的数据表明,TNFR2可能是无症状吸烟者和已戒烟者COPD的一个可能标志物。尽管吸烟者和早期COPD患者呈现出其他全身炎症标志物(如CRP)和氧化应激(通过AGEs测量)升高,但它们并不能区分吸烟者和COPD患者。