Deykin A, Belostotsky O, Hong C, Massaro A F, Lilly C M, Israel E
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Respir Crit Care Med. 2000 Nov;162(5):1685-9. doi: 10.1164/ajrccm.162.5.9911081.
Nitric oxide (NO) is a molecular gas that can be recovered in higher levels from the exhaled gas of subjects with asthma than from subjects without asthma. However, the precise mechanisms responsible of promoting increased fraction of expired nitric oxide (FE(NO)) in asthma are unknown. As leukotriene antagonism has been shown to reduce FE(NO) in patients with asthma, we hypothesized that leukotrienes mediate the increased FE(NO) encountered in this condition. Furthermore, because leukotriene antagonism stabilizes serum eosinophil markers during reductions in inhaled corticosteroid doses, and FE(NO) has been shown to correlate with sputum eosinophils in asthma, we reasoned that the effect of leukotrienes on FE(NO) might be mediated by eosinophils recruited to the airway by leukotrienes. To test this hypothesis, we performed methacholine and leukotriene (LT) E(4) bronchoprovocation challenges in 16 subjects with atopic asthma and measured FE(NO) and sputum differential counts before and after bronchoprovocation. We then compared FE(NO) in the seven subjects who developed increased sputum eosinophils following LTE(4) inhalation with values measured after methacholine inhalation in these seven subjects. Following LTE(4) inhalation, eosinophils rose from 4.01 +/- 0.89% pre-LTE(4) to 8.33 +/- 1.52% post-LTE(4). The mean change in sputum eosinophils from baseline after LTE(4) inhalation was larger than that after methacholine inhalation (+4.31 +/- 1.25% versus -1.14 +/- 0.93%). After LTE(4) inhalation, FE(NO) levels did not differ from prechallenge baseline or from levels following methacholine inhalation (ANOVA p > 0.05). These data indicate that neither LTE(4) nor recruitment of eosinophils into the airway by LTE(4) is a sufficient stimulus to acutely increase FE(NO) in subjects with asthma.
一氧化氮（NO）是一种分子气体，与无哮喘的受试者相比，哮喘患者呼出气体中可检测到更高水平的NO。然而，哮喘患者呼出一氧化氮分数（FE(NO)）升高的确切机制尚不清楚。由于白三烯拮抗剂已被证明可降低哮喘患者的FE(NO)，我们推测白三烯介导了这种情况下FE(NO)的升高。此外，由于白三烯拮抗剂在吸入性糖皮质激素剂量减少期间可稳定血清嗜酸性粒细胞标志物，并且FE(NO)已被证明与哮喘患者痰液中的嗜酸性粒细胞相关，我们推断白三烯对FE(NO)的影响可能由白三烯募集到气道的嗜酸性粒细胞介导。为了验证这一假设，我们对16名特应性哮喘患者进行了乙酰甲胆碱和白三烯（LT）E(4)支气管激发试验，并在支气管激发试验前后测量了FE(NO)和痰液分类计数。然后，我们将7名吸入LTE(4)后痰液嗜酸性粒细胞增加的受试者的FE(NO)值与这7名受试者吸入乙酰甲胆碱后的测量值进行了比较。吸入LTE(4)后，嗜酸性粒细胞从LTE(4)前的4.01±0.89%升至LTE(4)后的8.33±1.52%。吸入LTE(4)后痰液嗜酸性粒细胞相对于基线的平均变化大于吸入乙酰甲胆碱后的变化（+4.31±1.25%对-1.14±0.93%）。吸入LTE(4)后，FE(NO)水平与激发前基线或吸入乙酰甲胆碱后的水平无差异（方差分析p>0.05）。这些数据表明，LTE(4)以及LTE(4)将嗜酸性粒细胞募集到气道中均不足以急性增加哮喘患者的FE(NO)。
