Department of Infectious Diseases and Imperial Fungal Science Network, Imperial College London, London.
Manchester Fungal Infection Group, University of Manchester, Manchester, UK.
Curr Opin Infect Dis. 2023 Apr 1;36(2):146-151. doi: 10.1097/QCO.0000000000000913.
Chronic pulmonary aspergillosis is a major global infection in individuals with preexisting structural lung diseases and those with immunodeficiencies, in particular cytokine defects. Current treatment options are confined to just three drug classes, the triazoles, the echinocandins and amphotericin B. However, antifungal resistance is rapidly emerging for the triazoles, the only available oral therapy for this chronic condition.
Fortunately, there are now a number of novel antifungals in the development pipeline, mostly now in Phase 3 studies, with a potential for the treatment of chronic pulmonary aspergillosis. However, almost all current randomized triazoles of novel antifungals are primarily undertaken in patients with invasive candidiasis or invasive mould infections. Given the poor outcomes from treatment with antifungals in chronic pulmonary aspergillosis, in part associated with triazole resistance, we urgently need clinical trials of novel agents either as monotherapy or in combination for this disease. In addition, there is an emerging understanding of the role of immunotherapies for the treatment of chronic pulmonary aspergillosis, especially in the context of cytokine defects. Therefore, better understanding of the role of adjunctive immunotherapies such as interferon-gamma is also required.
In this review, we give an overview of current management of chronic pulmonary aspergillosis, and novel antifungals and immunotherapies for the future.
慢性肺曲霉病是一种主要的全球性感染,发生于存在结构性肺病和免疫缺陷的个体,特别是细胞因子缺陷的个体。目前的治疗方案仅限于三类药物,即三唑类、棘白菌素类和两性霉素 B。然而,抗真菌耐药性正在迅速出现,三唑类是这种慢性疾病唯一可用的口服治疗药物。
幸运的是,目前有许多新型抗真菌药物正在研发中,其中大多数目前处于 3 期研究阶段,有可能用于治疗慢性肺曲霉病。然而,几乎所有目前正在进行的新型抗真菌药物的随机三唑类药物试验主要是在侵袭性念珠菌病或侵袭性霉菌感染患者中进行的。鉴于抗真菌药物在慢性肺曲霉病中的治疗效果不佳,部分原因与三唑类耐药性有关,我们迫切需要针对这种疾病进行新型药物的临床试验,无论是单药治疗还是联合治疗。此外,人们越来越了解免疫疗法在治疗慢性肺曲霉病中的作用,特别是在细胞因子缺陷的情况下。因此,还需要更好地了解辅助免疫疗法(如干扰素-γ)的作用。
在这篇综述中,我们概述了慢性肺曲霉病的当前治疗方法,以及未来的新型抗真菌药物和免疫疗法。