Rytilä Paula, Rehn Tiina, Ilumets Helen, Rouhos Annamari, Sovijärvi Anssi, Myllärniemi Marjukka, Kinnula Vuokko L
Division of Allergology, University of Helsinki, Helsinki, Finland.
Respir Res. 2006 Apr 28;7(1):69. doi: 10.1186/1465-9921-7-69.
Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.
Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry. Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.
FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.
Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD.
慢性阻塞性肺疾病（COPD）与氧化应激和亚硝化应激增加有关。我们研究的目的是评估这些因素在健康吸烟者和无气道阻塞的有症状吸烟者（即GOLD 0期COPD个体）气道中的重要性。
收集了22名当前吸烟者（13名无任何呼吸道症状的健康吸烟者和9名有症状即0期COPD患者）以及22名年龄匹配的健康非吸烟者（11名从不吸烟者和11名既往吸烟者）的呼出一氧化氮（FENO）和诱导痰样本。通过免疫细胞化学分析细胞涂片上的痰液细胞分类计数以及诱导型一氧化氮合酶（iNOS）、髓过氧化物酶（MPO）、硝基酪氨酸和4-羟基壬烯醛（4-HNE）的表达。通过ELISA法检测痰液上清液中的嗜酸性粒细胞阳离子蛋白（ECP）和乳铁蛋白。
与非吸烟者相比，吸烟者的FENO显著降低，平均值（标准差）为11.0（6.7）ppb，而非吸烟者为22.9（10.0），p<0.0001。与非吸烟者相比，诱导痰显示吸烟者的中性粒细胞水平升高（p = 0.01）以及iNOS（p = 0.004）、MPO（p = 0.003）、硝基酪氨酸（p = 0.003）和4-HNE（p = 0.03）阳性细胞数量增加。吸烟者痰液中的乳铁蛋白水平也高于非吸烟者（p = 0.02）。此外，我们注意到FENO与1）总中性粒细胞（r = -0.367，p = 0.02）、2）iNOS阳性细胞（r = -0.503，p = 0.005）、3）MPO（r = -0.547，p = 0.008）和4）硝基酪氨酸（r = -0.424，p = 0.03）之间存在四个负相关。然而，从不吸烟者和既往吸烟者之间或健康吸烟者和0期COPD患者之间未发现主要差异。
我们的结果清楚地表明，与非吸烟者相比，当前吸烟者中氧化/亚硝化应激的几种标志物增加，并且在无症状吸烟者和GOLD 0期COPD受试者之间这些生物标志物未观察到主要差异。
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