Huang Junfeng, Xie Shuojia, Gao Yuewen, Lin Zikai, Xu Zhe, Lin Jinsheng, He Linzhi, Chen Gengjia, Zheng Ziwen, Xu Zhixing, Chen Jingyan, Guo Jiaming, Wu Zhile, Duan Ailing, Luo Weizhan, Song Xinyu, Li Shiyue
Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou Medical University, Guangzhou, Guangdong, China.
Orphanet J Rare Dis. 2025 Mar 4;20(1):102. doi: 10.1186/s13023-025-03617-3.
Pulmonary Alveolar Proteinosis (PAP) is a rare interstitial lung disease with diverse clinical manifestations and outcomes. However, there are limited data on the heterogeneity of PAP, as well as its prognosis, cause of death and genetic mechanisms. This study aims to elucidate mortality, prognostic features, and genetic mechanisms in patients with PAP.
The individual patient data of clinical and mortality were obtained by summarizing the published cases series. Patients with PAP were classified using K-means clustering, and logistic regression identified prognostic factors affecting outcomes. Inheritance and related mechanism of PAP were described by summarizing PAP related genes and enrichment analysis.
Our analysis included 3278 patients from 295 reports, with 88.6% diagnosed with idiopathic PAP (IPAP). Twelve major categories of cause were counted from 312 deaths (mortality: 9.5%), the most common of which were respiratory failure (45.8%) and lung infections (18.3%). Three symptom-related clusters were identified, and patients with multiple symptoms appeared to have worse mortality than those with single or no symptoms (p < 0.05). Non-secondary patterns (OR 2.87, p = 0.003), whole lung lavage (OR 0.15, p < 0.001), and effective GM-CSF therapy (OR 0.08, p < 0.001) are prognostic factors associated with decreased mortality. Additionally, 134 significant genes related to PAP development were identified, highlighting the roles of immune response and lipid metabolism.
This study comprehensively describes the clinical characteristics cause of death, prognosis and associated factors based on the global PAP population. The significant phenotype heterogeneity highlighting the importance of long-term prognosis and individualized management for patients with PAP.
肺泡蛋白沉积症（PAP）是一种罕见的间质性肺疾病，临床表现和结局多样。然而，关于PAP的异质性、预后、死亡原因及遗传机制的数据有限。本研究旨在阐明PAP患者的死亡率、预后特征及遗传机制。
通过总结已发表的病例系列获取临床和死亡的个体患者数据。采用K均值聚类对PAP患者进行分类，并通过逻辑回归确定影响结局的预后因素。通过总结PAP相关基因及富集分析来描述PAP的遗传方式及相关机制。
我们的分析纳入了来自295篇报告的3278例患者，其中88.6%被诊断为特发性PAP（IPAP）。从312例死亡病例（死亡率：9.5%）中统计出12大类死因，最常见的是呼吸衰竭（45.8%）和肺部感染（18.3%）。识别出三个与症状相关的聚类，有多种症状的患者死亡率似乎高于有单一症状或无症状的患者（p<0.05）。非继发性模式（比值比2.87，p=0.003）、全肺灌洗（比值比0.15，p<0.001）和有效的粒细胞-巨噬细胞集落刺激因子治疗（比值比0.08，p<0.001）是与死亡率降低相关的预后因素。此外，鉴定出134个与PAP发生相关的重要基因，突出了免疫反应和脂质代谢的作用。
本研究基于全球PAP人群全面描述了临床特征、死亡原因、预后及相关因素。显著的表型异质性凸显了PAP患者长期预后和个体化管理的重要性。
