囊性纤维化急性加重期的氧化应激和脂质衍生的炎症介质

Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis.

作者信息

Reid David W, Misso Neil, Aggarwal Shashi, Thompson Philip J, Walters E Haydn

机构信息

Cardio-Respiratory Research Group, University of Tasmania Medical School, Hobart, Tasmania, Australia.

出版信息

Respirology. 2007 Jan;12(1):63-9. doi: 10.1111/j.1440-1843.2006.00962.x.

DOI:10.1111/j.1440-1843.2006.00962.x

PMID:17207027

Abstract

BACKGROUND AND OBJECTIVE

In cystic fibrosis (CF) very few studies have assessed sputum 8-iso-PGF2alpha levels during pulmonary exacerbations as a direct measure of airway oxidative stress. The role of other lipid-derived inflammatory mediators, such as the cysteinyl leukotrienes (cys-LTs) and prostaglandin (PG)-E2, during exacerbations is also poorly defined and the effect of conventional antibiotic therapy on these components of the inflammatory process is unclear.

METHODS

Sputum 8-iso-PGF2alpha, total cys-LT and PGE2 levels were measured in 17 CF patients experiencing a pulmonary exacerbation and repeated analysis were performed in 15 of these patients after antibiotic treatment. Eight stable CF and nine healthy subjects provided control data.

RESULTS

Sputum 8-iso-PGF2alpha was significantly elevated in acute, but not stable CF patients versus healthy controls (P < 0.001). Similarly, sputum cys-LT and PGE2 levels were increased in acute compared with stable CF patients and healthy controls (P <or= 0.001). Although substantially lower than in acute patients, sputum cys-LT levels in stable patients were also significantly higher than in normal controls (P = 0.01). There were strong associations between cys-LT levels and sputum total cell counts, and blood neutrophils in acute patients (r2 = 0.53, P = 0.001 and r2 = 0.33, P < 0.05, respectively). Overall in the CF patients, FEV1% predicted was strongly and negatively correlated with sputum 8-iso-PGF2alpha (r2 = 0.34, P = 0.006), cys-LT (r2 = 0.40, P = 0.002) and PGE2 (r2 = 0.52, P < 0.001) levels. Antibiotic treatment reduced sputum total cell count (P = 0.03), but did not affect 8-iso-PGF2alpha, cys-LT or PGE2 levels.

CONCLUSIONS

CF exacerbations are characterized by increased oxidative stress and sputum concentrations of bioactive lipid mediators. Treatment does not modulate these aspects of inflammation and more targeted therapy needs further study.

摘要

背景与目的

在囊性纤维化（CF）中，很少有研究评估肺部加重期痰液中8-异前列腺素F2α（8-iso-PGF2α）水平，以作为气道氧化应激的直接指标。其他脂质衍生的炎症介质，如半胱氨酰白三烯（cys-LTs）和前列腺素（PG）-E2在加重期的作用也尚未明确，传统抗生素治疗对炎症过程中这些成分的影响尚不清楚。

方法

对17例经历肺部加重期的CF患者的痰液8-iso-PGF2α、总cys-LT和PGE2水平进行了检测，并对其中15例患者在抗生素治疗后进行了重复分析。8例病情稳定的CF患者和9名健康受试者提供了对照数据。

结果

与健康对照相比，急性加重期CF患者痰液中的8-iso-PGF2α显著升高，但病情稳定的CF患者则无此现象（P < 0.001）。同样，与病情稳定的CF患者及健康对照相比，急性加重期患者痰液中的cys-LT和PGE2水平升高（P≤0.001）。虽然稳定期患者痰液中的cys-LT水平远低于急性加重期患者，但仍显著高于正常对照（P = 0.01）。急性加重期患者的cys-LT水平与痰液总细胞计数及血液中性粒细胞之间存在强相关性（r2 = 0.53，P = 0.001；r2 = 0.33，P < 0.05）。总体而言，CF患者中，预测的第1秒用力呼气容积（FEV1）百分比与痰液8-iso-PGF2α（r2 = 0.34，P = 0.006）、cys-LT（r2 = 0.40，P = 0.002）和PGE2（r2 = 0.52，P < 0.001）水平呈强负相关。抗生素治疗可降低痰液总细胞计数（P = 0.03），但不影响8-iso-PGF2α、cys-LT或PGE2水平。