哮喘联盟

    理论基础：哮喘治疗指南指出，上呼吸道感染是哮喘失控的一个危险因素。亲离子性核苷酸受体P2X(7)调节划分急性炎症的局限化和对气道病原体的免疫反应。
    目的：假设感冒期间，P2X(7)功能的变异引起嗜中性粒细胞性气道炎症，导致急性哮喘。
    方法：选取自然感冒初期的哮喘志愿者，对其进行观察至恢复期，评价其症状、肺功能和气道炎症。血液样本中P2X(7)孔活性通过遗传学验证的流式细胞分析检测。
    检测主要结果：35名轻-中度过敏性哮喘患者参与该研究，31名患者完成所有试验。P2X(7)功能与感冒期间鼻腔灌洗液中性粒细胞计数变化有关（R(s) = 0.514, P = 0.004），与哮喘症状变化负相关（R(s) = -0.486, P = 0.009）。记录的呼气流量峰值变化、感冒前激素的使用以及P2X(7)孔功能是哮喘症状的多因素预测因子（P 分别为= 0.001, < 0.001及= 0.003）。P2X(7)活性下降与哮喘失控增加相关（OR：11.0; 95% CI, 1.1-106.4），对吸入激素和鼻病毒进行校正不能改变这一的结果（OR，15.0）。
    结论：全血P2X(7)孔分析能鉴别丧失功能基因型的患者，可在流行病学研究中采用该分析。P2X(7)孔活性降低可能为病毒诱导哮喘失控的一个新的生物标记物。

（苏楠审 校）
Denlinger LC, et al. Am J Respir Crit Care Med. 2009 Feb 15;179(4):265-270.

Attenuated P2X7 pore function as a risk factor for virus-induced loss of asthma control.

RATIONALE: Upper respiratory tract infection is a guideline accepted risk domain for the loss of asthma control. The ionotrophic nucleotide receptor P2X(7) regulates compartmentalized acute inflammation and the immune response to airway pathogens.
OBJECTIVES: We hypothesized that variability in P2X(7) function contributes to neutrophilic airway inflammation during a cold and thereby is linked to acute asthma.
METHODS: Research volunteers with asthma were enrolled at the onset of a naturally occurring cold and monitored through convalescence, assessing symptoms, lung function, and airway inflammation. P2X(7) pore activity in whole blood samples was measured using a genomically validated flow cytometric assay.
MEASUREMENTS AND MAIN RESULTS: Thirty-five participants with mild to moderate allergic asthma were enrolled and 31 completed all visits. P2X(7) pore function correlated with the change in nasal lavage neutrophil counts during the cold (R(s) = 0.514, P = 0.004) and was inversely related to the change in asthma symptoms (R(s) = -0.486, P = 0.009). The change in peak expiratory flow recordings, precold use of inhaled corticosteroids, and P2X(7) pore function were multivariate predictors of asthma symptoms (P = 0.001, < 0.001 and = 0.003 respectively). Attenuated P2X(7) activity was associated with the risk of losing asthma control (crude odds ratio, 11.0; 95% confidence interval, 1.1-106.4) even after adjustment for inhaled corticosteroids and rhinovirus (odds ratio, 15.0).
CONCLUSIONS: A whole blood P2X(7) pore assay robustly identifies participants with loss-of-function genotypes. Using this assay as an epidemiologic tool, attenuated P2X(7) pore activity may be a novel biomarker of virus-induced loss of asthma control.