Background

Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA.

Methods

A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023. We included clinical studies, observational studies, controlled trials, and abstracts. Case reports, animal studies, letters, news, and literature reviews were excluded. Authors of studies published since 2016 were also contacted to obtain anonymised individual patient data (IPD); for other studies, summary estimates were extracted. Subgroup analysis was done for differences in overall 1-year and 5-year mortality, data source, study design, risk of bias, country, Human Development Index, age groups, and the underlying lung disease. We used random-effects meta-analyses to estimate pooled mortality rates. Subgroup analyses and meta-regression were done to explore sources of heterogeneity. One-stage meta-analysis with a stratified Cox proportional hazards model was used to estimate the univariable and hazards for mortality, adjusting for age, sex, type of CPA, treatment, and underlying pulmonary comorbidities. This study was registered with PROSPERO (CRD42023453447).

Findings

We included 79 studies involving 8778 patients in the overall pooled analysis and 15 studies involving 1859 patients in the IPD meta-analysis. Pooled mortality (from 70 studies) was estimated at 27% overall (95% CI 22–32; I² =95·4%), 15% at 1 year (11–19; I² =91·6%), and 32% at 5 years (25–39; I² =94·3%). Overall mortality in patients with CPA with pulmonary tuberculosis as the predominant predisposing condition was 25% (16–35; I² =87·5%; 20 studies) and with chronic obstructive pulmonary disease was 35% (22–49; I² =89·7%; 14 studies). Mortality in cohorts of patients who underwent surgical resection was low at 3% (2–4). In the multivariable analysis, among predisposing respiratory conditions, pulmonary tuberculosis history had the lowest mortality hazard (relative to an absence of the disease at baseline), whereas worse outcomes were seen with underlying malignancy; subacute invasive pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis subtypes of CPA were also significantly associated with increased mortality relative to simple aspergilloma on multivariable analysis. Mortality hazard increased by 25% with each decade of age (adjusted hazard ratio 1·25 [95% CI 1·14–1·36], p<0·0001).

Interpretation

CPA is associated with substantial mortality. Advancing age, CPA subtype, and underlying comorbidities are important predictors of mortality. Future studies should focus on identifying appropriate treatment strategies tailored to different risk groups.

Funding

None.

中文翻译：

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慢性肺曲霉菌病的死亡率：系统评价和个体患者数据荟萃分析

 背景

尽管接受了抗真菌治疗，但慢性肺曲霉病 （CPA） 与较高的发病率和死亡率相关。我们进行了系统评价和荟萃分析，以评估 CPA 的死亡率及其预测因素。

 方法

在 MEDLINE （PubMed）、Scopus、Embase 和 Web of Science 中进行了系统文献检索，以确定从数据库建库到 2023 年 8 月 15 日的英文研究，报告 CPA 死亡率。我们纳入了临床研究、观察性研究、对照试验和摘要。病例报告、动物研究、信件、新闻和文献综述被排除在外。还联系了自 2016 年以来发表的研究的作者以获取匿名的个体患者数据 （IPD）;对于其他研究，提取了汇总估计值。对总体 1 年和 5 年死亡率、数据来源、研究设计、偏倚风险、国家、人类发展指数、年龄组和潜在肺部疾病的差异进行亚组分析。我们使用随机效应meta分析来估计合并死亡率。进行亚组分析和 meta 回归以探索异质性的来源。采用分层 Cox 比例风险模型的一期荟萃分析来估计死亡率的单变量和风险，调整年龄、性别、CPA 类型、治疗和潜在的肺部合并症。这项研究在 PROSPERO （CRD42023453447） 注册。

 发现

我们在整体汇总分析中纳入了 79 项研究，涉及 8778 名患者，在 IPD meta 分析中纳入了 15 项研究，涉及 1859 名患者。总体死亡率（来自 70 项研究）估计为 27% （95% CI 22-32;I² =95·4%），1 岁时为 15% （11-19;I² =91·6%），5 岁时为 32% （25-39;I² =94·3%）。以肺结核为主要诱发因素的 CPA 患者的总体死亡率为 25% （16-35;I² =87·5%;20 项研究）和慢性阻塞性肺病患者为 35% （22-49;I² =89·7%;14 项研究）。接受手术切除的患者队列的死亡率较低，为 3% （2-4）。在多变量分析中，在易感呼吸系统疾病中，肺结核病史的死亡风险最低（相对于基线时没有疾病），而潜在恶性肿瘤的结局更差;在多变量分析中，CPA 的亚急性侵袭性肺曲霉病和慢性空洞性肺曲霉病亚型也与相对于单纯曲霉球的死亡率增加显著相关。每10岁，死亡风险增加25%（校正风险比1·25 [95% CI 1·14–1·36]，p<0·0001）。

 解释

CPA 与大量死亡率相关。年龄增长、CPA 亚型和潜在合并症是死亡率的重要预测指标。未来的研究应侧重于确定针对不同风险群体的适当治疗策略。

 资金

 没有。