Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Lao PDR.
National Aspergillosis Centre, Wythenshawe Hospital, Manchester University Foundation Trust, Manchester, United Kingdom.
Semin Respir Crit Care Med. 2024 Feb;45(1):88-101. doi: 10.1055/s-0043-1776914. Epub 2023 Dec 28.
Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of adaptation in the lung environment, the contribution of non- species, and the role of new antifungal agents, immunotherapy, and combination therapy.
慢性肺曲霉病（CPA）是指在慢性肺部疾病患者的肺部存在和局部增殖的生物体引起的多种临床综合征。与二十年前相比，CPA 更为常见。尽管许多国家的最近研究强调了高危人群中的高患病率，但对其的认识仍然很差。在中低收入国家，CPA 可能被误诊为结核病（TB）并进行治疗。此外，CPA 也可能在成功治疗 TB 后发生。冠状病毒病大流行导致结核病护理的提供受到严重干扰，可能导致更广泛的肺部损伤，从而增加 CPA 的风险。虽然 CPA 是指各种综合征，但典型表现为慢性空洞性肺曲霉病，其表现为一个或多个进行性空洞，伴有或不伴有真菌球，并伴有全身和呼吸系统症状至少 3 个月。诊断依赖于血清中的免疫球蛋白 G，因为痰培养缺乏敏感性。鉴别诊断包括分枝杆菌感染、细菌性肺脓肿或坏死性肺炎、肺癌和地方性真菌。CPA 中抗真菌治疗的目的是改善症状和生活质量，阻止进展，并可能逆转影像学变化。目前的建议是治疗 6 个月，尽管在实践中，许多患者仍需要长期治疗。改善可能表现为体重增加和症状改善，如咳痰、咯血和疲劳。在诊断不确定、大量咯血以及担心对治疗无反应时，应考虑手术治疗。伊曲康唑和伏立康唑是一线唑类药物，现在积累了更多关于泊沙康唑和伊曲康唑的经验。副作用频繁，需要仔细监测，包括治疗药物监测。在唑类药物不耐受或耐药时，如治疗后常发生，使用棘白菌素类和两性霉素 B 等静脉用抗真菌药物。在大约 20%的病例中，在完成抗真菌治疗后会出现复发，主要是在双侧、高负荷疾病中。已经确定了一些研究重点，包括对与 CPA 相关的免疫缺陷和遗传变异、肺部环境中适应的发病机制、非物种的贡献以及新型抗真菌药物、免疫疗法和联合疗法的作用的特征描述。
