Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization The Fungal Asthma Sensitization Trial (FAST) Study
Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization The Fungal Asthma Sensitization Trial (FAST) Study
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DOI：
10.1164/rccm.200805-737oc
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发表时间：
2009-01-01
影响因子：
24.7
通讯作者：
Niven, Robert M.
中科院分区：
文献类型：
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作者：
Denning, David W.;O'Driscoll, B. Ronan;Niven, Robert M.
理由：一些严重哮喘患者对一种或多种真菌具有免疫敏感性，这种临床实体被归类为真菌致敏性严重哮喘（SAFS）。目前尚不清楚 SAFS 是否对抗真菌治疗有反应。目的：评估 SAFS 对口服伊曲康唑的反应。方法：招募通过皮肤点刺或特异性 IgE 检测对七种真菌中的至少一种敏感的严重哮喘患者。所有患者的总 IgE 均低于 1,000 IU/ml，且曲霉沉淀素均为阴性。他们接受口服伊曲康唑（200 mg，每日两次）或安慰剂治疗，持续 32 周，随访 16 周。 测量和主要结果：主要终点是哮喘生活质量问卷 (AQLQ) 评分的变化，鼻炎评分、总 IgE 和呼吸功能作为次要终点。共有 58 名患者入组，其中 41% 在前一年住院过。基线平均 AQLQ 得分为 4.13（范围，1-7）。 32 周时，抗真菌组的 AQLQ 评分改善（95% 置信区间）为 +0.85（0.28，1.41），而安慰剂组的变化为 -0.01（-0.43，0.42）（P = 0.014）。抗真菌药物组的鼻炎评分有所改善（-0.43），而安慰剂组的鼻炎评分则恶化（+0.17）（P = 0.013）。抗真菌组的早晨峰值流量有所改善（20.8 升/分钟，P = 0.028）。抗真菌组血清总 IgE 降低（-51 IU/ml），但安慰剂组升高（+30 IU/ml）（P = 0.001）。未观察到严重不良事件，但 7 名患者出现需要停药的不良事件，其中 5 名患者属于抗真菌组。结论：根据约 60% 患者生活质量的大幅改善来判断，SAFS 对口服抗真菌治疗有反应。临床试验已在 www.controlled-tfials.com 注册 (ISRCTN61552714)。
Rationale: Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy.Objectives: To evaluate the response of SAFS to oral itraconazole.Methods: Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testing were recruited. All had total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks.Measurements and Main Results: The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. Baseline mean AQLQ score was 4.13 (range, 1-7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a -0.01 (-0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (-0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group (-51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group.Conclusions: SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients. Clinical trial registered with www.controlled-tfials.com (ISRCTN61552714).