迟发型哮喘崭新的危险因素：一项关于宿主抗氧化防御的巢式病例对照研究
2015/06/10
摘要
理由：宿主抗氧化防御，包括酶的抗氧化活性与非酶抗氧化的营养素，均与哮喘发病机制相关。有关抗氧化防御与发生成人哮喘的关系的研究要么使用问卷调查来检测抗氧化剂，要么不考虑宿主防御酶方面。
目标：我们设计了第一项并有足够检验效能的研究，来探索抗氧化防御与成人哮喘发生的相关性。
方法：此研究为巢式病例对照研究，随访了8年在基线时无哮喘的上海女性（年龄40～70岁）。对有哮喘症状的女性采用金标准测试来前瞻性的确诊哮喘，同时匹配2例无哮喘症状的对照受试者。
测量和主要结果：基线尿F2-异前列腺素，血浆抗氧化营养素浓度（维生素E，黄嘌呤，胡萝卜素，番茄红素），和抗氧化酶活性（血小板活化因子乙酰水解酶[platelet-activating factor acetylhydrolase：PAF-AH]和超氧化物歧化酶（superoxide dismutase：SOD））从疾病发病前采集的血浆样本中进行检测。在65,372名妇女中，150例（0.24％）发展为哮喘。哮喘发病前F2-异前列腺素水平在病例组与对照组之间无显著差异。双倍的α-生育酚浓度与PAF-AH活性分别降低了50%和37％哮喘发生的风险（α-生育酚的风险：校正后的比值比=0.52; 95％置信区间：0.32-0.84; PAF-AH：校正后的比值比= 0.63; 95％置信区间：0.42-0.93）。
结论：在这项前瞻性研究中，正常参考范围的α-生育酚，和PAF-AH酶活性均可降低哮喘的发生。这些可干预的危险因素，可以作为一种有效的策略来预防哮喘的发生。
(张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med. 2015; 191: 45–53.）
New Risk Factors for Adult-Onset Incident Asthma
A Nested Case– Control Study of Host Antioxidant Defense
Larkin EK, Gao YT, Gebretsadik T, Hartman TJ, Wu PS, Wen WQ, Yang G, Chunxue Bai CX, Jin ML, Roberts II LJ, Gross M, Shu XO, Hartert TV.
Am J Respir Crit Care Med. 2015; 191: 45–53.
ABSTRACT
RATIONALE: Host antioxidant defense, consisting of enzymatic antioxidant activity and nonenzymatic antioxidant micronutrients, is implicated in asthma pathogenesis. Studies of antioxidant defense and adult incident asthma have either used measures of antioxidants estimated from questionnaires or not considered enzymatic aspects of host defense.
OBJECTIVES: We conducted the first study designed and powered to investigate the association of antioxidant defenses on adult incident asthma.
METHODS: In a nested case–control study, we followed Shanghai women (aged 40–70 years) without prevalent asthma at baseline, over 8 years. Subjects with incident asthma were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic control subjects.
MEASUREMENTS AND MAIN RESULTS: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthines, carotenes, and lycopene), and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected before disease onset. Among 65,372 women, 150 (0.24%) developed asthma. F2- isoprostane levels before asthma onset were not different between cases and control subjects. Doubling of α-tocopherol concentrations and PAF-AH activity was associated with 50 and 37% decreased risk of incident asthma (α-tocopherol: adjusted odds ratio = 0.52; 95% confidence interval, 0.32–0.84; PAF-AH: adjusted odds ratio = 0.63; 95% confidence interval, 0.42–0.93).
CONCLUSIONS: In this prospective study, α-tocopherol, within normal reference ranges, and PAF-AH enzymatic activity were associated with decreased asthma development. These modifiable risk factors may be an effective strategy to test for primary asthma prevention.
