Voriconazole and Posaconazole Improve Asthma Severity in Allergic Bronchopulmonary Aspergillosis and Severe Asthma with Fungal Sensitization
Voriconazole and Posaconazole Improve Asthma Severity in Allergic Bronchopulmonary Aspergillosis and Severe Asthma with Fungal Sensitization
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DOI：
10.3109/02770903.2012.662568
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发表时间：
2012-05-01
影响因子：
1.9
通讯作者：
Denning, David W.
中科院分区：
文献类型：
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作者：
Chishimba, Livingstone;Niven, Robert M.;Denning, David W.
理论基础和目标。重症哮喘合并真菌致敏(SAFS)和过敏性支气管肺曲霉菌病(ABPA)是进行性变态反应性真菌性肺部疾病，其有效治疗方法尚不清楚。目前伊曲康唑的治疗与40%的失败率和不良事件(AEs)相关。我们评估了伏立康唑或泊沙康唑作为二线和三线治疗的效果。方法：研究方法。我们对使用伏立康唑或泊沙康唑治疗ABPA或SAFS的成人哮喘患者进行了回顾。临床、放射学和免疫学评估用于评估疗效。结果。其中ABPA(20例)或SAFS(5例)25例，男性10例，中位年龄58岁。所有患者均未用伊曲康唑(n=14)或发生AEs(n=11)。分析了33个疗程，其中伏立康唑24个疗程，泊沙康唑9个疗程。伏立康唑在3个月、6个月和12个月的临床反应分别为17/24(70%)、15/20(75%)和12/16(75%)，而泊沙康唑在3、6和12个月时分别为7/9(78%)和7/9(78%)。24例患者中有18例(75%)停用糖皮质激素(OCS)，其中12例在治疗后3个月内停用。在24例哮喘患者中，9例(38%)哮喘严重程度从重度降至中度(N 8)，中度至轻度(N 1)。OCS和短效β-2激动剂的使用、哮喘引起的医疗保健利用以及整体健康状况的改善都有显著减少。此外，9个月时总IgE和12个月时烟曲霉菌放射过敏吸附试验IgE的免疫学标志物均有显著下降(p=0.0056)。服用伏立康唑的23名患者中有6名(26%)的不良反应需要在6个月前停药，而服用泊沙康唑的患者中没有一人需要停药(p=.15)。4例复发(57%)，1例在停药后3个月复发，3例在停药后12个月复发。结论。伏立康唑和泊沙康唑都是治疗SAFS和ABPA的潜在有效的替代治疗方案，可能会改善哮喘控制并降低严重性，尽管需要更大规模的前瞻性研究来支持这些回顾性研究结果。
Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n 8) and moderate to mild (n 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.