Martin Richard J, Szefler Stanley J, King Tonya S, Kraft Monica, Boushey Homer A, Chinchilli Vernon M, Craig Timothy J, Dimango Emily A, Deykin Aaron, Fahy John V, Israel Elliot, Lazarus Stephen C, Lemanske Robert F, Leone Frank T, Pesola Gene R, Peters Stephen P, Sorkness Christine A, Szwejbka Lisa A, Wechsler Michael E
National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2007 Jan;119(1):73-80. doi: 10.1016/j.jaci.2006.10.035.
Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids.
To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks).
Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control.
Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (<or=5%) determined the longer-term need for steroids. For the nonresponders, asthma control remained unchanged whether inhaled corticosteroids were continued or were substituted with a placebo (P = .99). The good short-term responders maintained asthma control longer-term only if maintained on inhaled steroids (P = .007).
The short-term response to inhaled corticosteroids with regard to FEV(1) improvement predicts long-term asthma control.
The decision to use long-term inhaled steroids could be based on a short-term trial. Different therapeutic strategies would need to be established for nonresponders.
尽管指南推荐对持续性哮喘进行抗炎治疗，但最近的研究表明，25%至35%的哮喘患者使用吸入性糖皮质激素后肺功能可能并无改善。
评估预测吸入性糖皮质激素短期（6周）反应的潜在生物标志物，并随后在更长时间段（额外16周）评估哮喘控制的反应者和无反应者。
83名未使用类固醇的哮喘患者参与了这项多中心研究。在为期6周的试验中，评估生物标志物和哮喘特征作为吸入性糖皮质激素反应的预测指标，以观察第一秒用力呼气容积（FEV₁）和乙酰甲胆碱激发试验浓度（PC₂₀）的变化。在此之后，进行额外的4个月试验以评估哮喘控制情况。
尽管多个基线预测指标与短期吸入性类固醇治疗成功后的改善存在显著相关性，但唯一强相关性（r≥±0.6）的指标是沙丁胺醇可逆性（r = 0.83；P <.001）、FEV₁/用力肺活量（r = -0.75；P <.001）以及预测的FEV₁百分比（r = -0.71；P <.001）。将短期吸入性类固醇试验中的受试者分为反应者（FEV₁改善>5%）和无反应者（≤5%），可确定长期类固醇治疗需求。对于无反应者，无论继续使用吸入性糖皮质激素还是用安慰剂替代，哮喘控制情况均无变化（P = 0.99）。良好的短期反应者只有在持续使用吸入性类固醇时才能长期维持哮喘控制（P = 0.007）。
吸入性糖皮质激素在FEV₁改善方面的短期反应可预测长期哮喘控制情况。
长期使用吸入性类固醇的决策可基于短期试验结果。对于无反应者，需要制定不同的治疗策略。
