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伏立康唑和泊沙康唑可改善变应性支气管肺曲霉病和伴有真菌致敏的重度哮喘的哮喘严重程度。

Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization.

作者信息

Chishimba Livingstone, Niven Robert M, Cooley John, Denning David W

机构信息

Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.

出版信息

J Asthma. 2012 May;49(4):423-33. doi: 10.3109/02770903.2012.662568. Epub 2012 Mar 2.

Abstract

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.

摘要

原理与目的。伴有真菌致敏的重度哮喘(SAFS)和变应性支气管肺曲霉病(ABPA)是进展性变应性真菌性肺部疾病,其有效治疗方法仍有待确立。目前使用伊曲康唑治疗的失败率为40%,且伴有不良事件(AE)。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。我们对接受伏立康唑或泊沙康唑治疗的ABPA或SAFS成年哮喘患者进行了回顾性研究。采用临床、影像学和免疫学评估来评估疗效。结果。共有25例患者,其中ABPA(n = 20)或SAFS(n = 5),男性10例,中位年龄 = 58岁。所有患者伊曲康唑治疗失败(n = 14)或出现AE(n = 11)。共分析了33个疗程的治疗,其中24个疗程使用伏立康唑,9个疗程使用泊沙康唑。伏立康唑治疗的患者在3个月时临床有效率为17/24(70%),6个月时为15/20(75%),12个月时为12/16(75%);泊沙康唑治疗的患者在3、6和12个月时的有效率分别为7/9(78%)。24例患者中有18例(75%)停用了口服糖皮质激素(OCS),其中12例在治疗3个月内停用。24例哮喘患者中有9例(38%)的哮喘严重程度从重度降至中度(n = 8),从中度降至轻度(n = 1)。OCS和短效β2激动剂的使用显著减少,因哮喘导致的医疗保健利用减少,总体健康状况得到改善。此外,总IgE在9个月时(p = .008)以及烟曲霉的放射变应原吸附试验IgE在12个月时(p = .0056)的免疫学标志物有统计学显著降低。接受伏立康唑治疗的23例患者中有6例(26%)在6个月前出现需要停药的AE,而接受泊沙康唑治疗的患者无一例出现(p = .15)。4例复发(57%),1例在停药后3个月复发,3例在12个月复发。结论。伏立康唑和泊沙康唑均可能是SAFS和ABPA潜在有效的替代治疗选择,可能改善哮喘控制并降低严重程度,不过需要更大规模的前瞻性研究来支持这些回顾性研究结果。

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