Maneechotesuwan Kittipong, Essilfie-Quaye Sarah, Kharitonov Sergei A, Adcock Ian M, Barnes Peter J
Airways Disease Section, Dovehouse St, London, SW3 6LY, UK.
Chest. 2007 Jul;132(1):98-105. doi: 10.1378/chest.06-2982. Epub 2007 Jun 5.
The role of neutrophils in exacerbations of asthma is poorly understood. We examined the effect of withdrawal of inhaled corticosteroids on sputum inflammatory indexes in a double-blind study in patients with moderate, stable asthma.
Following a 2-week run in period, 24 subjects were randomized to receive either budesonide (400 microg bid) or placebo, and the study was continued for another 10 weeks.
Loss of asthma control developed in 8 of 12 patients over the 10-week period of steroid withdrawal, whereas only 1 of 10 patients with budesonide treatment had exacerbations. Those with an exacerbation had increased sputum interleukin (IL)-8 (p < 0.0001) and increased sputum neutrophil numbers (p < 0.0001) compared to those without an exacerbation. The significant elevation in sputum IL-8 and neutrophil counts initially occurred 2 weeks prior to an exacerbation. Sputum neutrophilia correlated positively with changes in IL-8 levels (r(2) = 0.76, p = 0.01).
Rapid withdrawal of inhaled corticosteroids results in an exacerbation of asthma that is preceded by an increase in sputum neutrophils and IL-8 concentrations, in contrast to an increase in eosinophils reported in previous studies in which inhaled steroids are slowly tapered.
中性粒细胞在哮喘急性发作中的作用尚不清楚。我们在一项针对中度稳定哮喘患者的双盲研究中，研究了停用吸入性糖皮质激素对痰液炎症指标的影响。
在为期2周的导入期后，24名受试者被随机分为接受布地奈德（400微克，每日两次）或安慰剂治疗，研究持续另外10周。
在停用类固醇的10周期间，12名患者中有8名出现哮喘控制不佳，而接受布地奈德治疗的10名患者中只有1名出现急性发作。与未发作的患者相比，发作的患者痰液白细胞介素（IL）-8升高（p<0.0001），痰液中性粒细胞数量增加（p<0.0001）。痰液IL-8和中性粒细胞计数的显著升高最初在发作前2周出现。痰液中性粒细胞增多与IL-8水平变化呈正相关（r²=0.76，p=0.01）。
与之前吸入性类固醇缓慢减量的研究中报道的嗜酸性粒细胞增加相反，快速停用吸入性糖皮质激素会导致哮喘急性发作，且发作前痰液中性粒细胞和IL-8浓度会升高。
