Rouhani Farshid N, Meitin Catherine A, Kaler Maryann, Miskinis-Hilligoss Dianne, Stylianou Mario, Levine Stewart J
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590, USA.
Respir Med. 2005 Sep;99(9):1175-82. doi: 10.1016/j.rmed.2005.02.031. Epub 2005 Mar 23.
To assess whether tumor necrosis factor (TNF) antagonism can attenuate eosinophilic airway inflammation in patients with mild-to-moderate allergic asthma.
Randomized, double-blind, placebo-controlled trial.
National Institutes of Health (NIH) Clinical Center.
Twenty-six patients with mild-to-moderate allergic asthma, receiving only inhaled beta-2-agonists, who demonstrated both an early and late phase response to inhalational allergen challenge.
Injection of a soluble TNF receptor (TNFR:Fc, etanercept, Enbrel) or placebo, 25mg subcutaneously, twice weekly for 2 weeks, followed by a bronchoscopic segmental allergen challenge.
The primary outcome measure was whether TNFR:Fc can access the lung and inhibit TNF bioactivity. Secondary outcome measures included pulmonary eosinophilia, Th2-type cytokines, and airway hyperresponsiveness.
Anti-TNF therapy was associated with transient hemiplegia in one patient, which resulted in suspension of the study. Data from the 21 participants who completed the study were analyzed. Following treatment, patients receiving anti-TNF therapy had significantly increased TNFR2 levels in epithelial lining fluid (ELF) (P<0.001), consistent with delivery of TNFR:Fc to the lung. TNF antagonism did not attenuate pulmonary eosinophilia and was associated with an increase in ELF IL-4 levels (P=0.033) at 24h following segmental allergen challenge. TNF antagonism was not associated with a change in airway hyperresponsiveness to methacholine.
TNF antagonism may not be effective for preventing allergen-mediated eosinophilic airway inflammation in mild-to-moderate asthmatics. Transient hemiplegia, which may mimic an evolving stroke, may be a potential toxicity of anti-TNF therapy.
评估肿瘤坏死因子（TNF）拮抗剂是否能减轻轻至中度过敏性哮喘患者的嗜酸性气道炎症。
随机、双盲、安慰剂对照试验。
美国国立卫生研究院（NIH）临床中心。
26例轻至中度过敏性哮喘患者，仅接受吸入性β2激动剂治疗，对吸入性过敏原激发试验表现出早期和晚期反应。
皮下注射可溶性TNF受体（TNFR:Fc，依那西普，恩利）或安慰剂，25mg，每周两次，共2周，随后进行支气管镜节段性过敏原激发试验。
主要结局指标是TNFR:Fc是否能进入肺部并抑制TNF生物活性。次要结局指标包括肺部嗜酸性粒细胞增多、Th2型细胞因子和气道高反应性。
一名患者接受抗TNF治疗后出现短暂性偏瘫，导致研究中止。对完成研究的21名参与者的数据进行了分析。治疗后，接受抗TNF治疗的患者上皮衬液（ELF）中的TNFR2水平显著升高（P<0.001），这与TNFR:Fc进入肺部一致。TNF拮抗作用并未减轻肺部嗜酸性粒细胞增多，且在节段性过敏原激发试验后24小时，与ELF中IL-4水平升高相关（P=0.033）。TNF拮抗作用与对乙酰甲胆碱的气道高反应性变化无关。
TNF拮抗作用可能对预防轻至中度哮喘患者过敏原介导的嗜酸性气道炎症无效。可能类似于进展性中风的短暂性偏瘫可能是抗TNF治疗的潜在毒性。
