囊性纤维化稳定期患者临床及炎症标志物与预后的关系

The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis.

作者信息

Downey Damian G, Martin S Lorraine, Dempster Martin, Moore John E, Keogan Mary T, Starcher Barry, Edgar Julia, Bilton Diana, Elborn J Stuart

机构信息

Adult Cystic Fibrosis Centre, Belfast City Hospital and Queens University, Belfast, Northern Ireland.

出版信息

Pediatr Pulmonol. 2007 Mar;42(3):216-20. doi: 10.1002/ppul.20553.

DOI:10.1002/ppul.20553

PMID:17238189

Abstract

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation. Pre-treatment measurements were used in this study. Demographics, sputum microbiology, heart rate, oxygen saturation, lung function were recorded. Blood samples were obtained for white blood count (WBC), C-Reactive Protein (CRP), and plasma neutrophil elastase/AAT complexes (pNEC). Neutrophil elastase (NE), neutrophil elastase/AAT complexes (sNEC), interleukin-8 (IL-8), TNF-receptor 1 (sTNFr), and myeloperoxidase (MPO) were measured in sputum and urinary desmosine concentration determined. Patients with Bc had significantly higher levels of pNEC, 332 +/- 91.4 ng/ml (mean +/- SEM) versus 106 +/- 18.2 ng/ml (P = 0.0005) and sNEC, 369 +/- 76.6 ng/ml versus 197 +/- 36.0 ng/ml compared to those who were not. Five deaths were reported at the end of 1 year, (four with Bc) (P = 0.011). Patients who subsequently died had significantly lower lung function FEV1, 1.2 +/- 0.2 L versus 2.0 +/- 0.1 L (P = 0.03) and FVC, 2 +/- 0.3 L versus 3.1 +/- 0.2 L (P = 0.01), compared to those that survived. There was significantly higher NE activity, 3.6 +/- 1.6 U/ml versus 1.5 +/- 0.6 U/ml (P = 0.03), pNEC, 274 +/- 99 ng/ml versus 142 +/- 30 ng/ml (P = 0.05), MPO, 163 +/- 62 mcg/ml versus 54 +/- 6.9 mcg/ml (P = 0.03), and urinary desmosines 108 +/- 19.9 pM/mg creatinine versus 51.1 +/- 3.3 pM/mg creatinine (P = 0.001), in those patients who subsequently died compared to those that survived. These data suggest there is increased neutrophil degranulation in patients infected with Bc and these patients have a poor outcome.

摘要

囊性纤维化患者生存率降低与第一秒用力呼气量（FEV1）、体重指数（BMI）以及洋葱伯克霍尔德菌复合体（BCC）感染有关。我们评估了血液、痰液和尿液中的炎症标志物与肺功能、BMI、洋葱伯克霍尔德菌（Bc）定植以及患者生存率之间的关系。39名病情稳定的囊性纤维化（CF）患者（其中10名感染Bc）参与了一项关于α-1抗胰蛋白酶对气道炎症影响的研究。本研究采用治疗前测量数据。记录了人口统计学信息、痰液微生物学、心率、血氧饱和度和肺功能。采集血样检测白细胞计数（WBC）、C反应蛋白（CRP）和血浆中性粒细胞弹性蛋白酶/AAT复合物（pNEC）。检测痰液中的中性粒细胞弹性蛋白酶（NE）、中性粒细胞弹性蛋白酶/AAT复合物（sNEC）、白细胞介素-8（IL-8）、肿瘤坏死因子受体1（sTNFr）以及髓过氧化物酶（MPO），并测定尿液中的锁链素浓度。与未感染Bc的患者相比，感染Bc的患者pNEC水平显著更高，分别为332±91.4 ng/ml（平均值±标准误）和106±18.2 ng/ml（P = 0.0005），sNEC水平分别为369±76.6 ng/ml和197±36.0 ng/ml。1年后报告了5例死亡病例（4例感染Bc）（P = 0.011）。与存活患者相比，随后死亡的患者肺功能FEV1显著更低，分别为1.2±0.2 L和2.0±0.1 L（P = 0.03），用力肺活量（FVC）分别为2±0.3 L和3.1±0.2 L（P = 0.01）。与存活患者相比，随后死亡的患者NE活性显著更高，分别为3.6±1.6 U/ml和1.5±0.6 U/ml（P = 0.03），pNEC分别为274±99 ng/ml和142±30 ng/ml（P = 0.05），MPO分别为163±62 mcg/ml和54±6.9 mcg/ml（P = 0.03），尿液锁链素分别为108±19.9 pM/mg肌酐和51.1±3.3 pM/mg肌酐（P = 0.001）。这些数据表明，感染Bc的患者中性粒细胞脱颗粒增加，且这些患者预后较差。