Phenotypic heterogeneity in mortality and prognosis of pulmonary alveolar proteinosis: a large-scale, global pooled analysis of individual-level data

Junfeng Huang; Shuojia Xie; Yuewen Gao; Zikai Lin; Zhe Xu; Jinsheng Lin; Linzhi He; Gengjia Chen; Ziwen Zheng; Zhixing Xu; Jingyan Chen; Jiaming Guo; Zhile Wu; Ailing Duan; Weizhan Luo; Xinyu Song; Shiyue Li

doi:10.1186/s13023-025-03617-3

Orphanet Journal of Rare Diseases (Mar 2025)

Phenotypic heterogeneity in mortality and prognosis of pulmonary alveolar proteinosis: a large-scale, global pooled analysis of individual-level data

Junfeng Huang,
Shuojia Xie,
Yuewen Gao,
Zikai Lin,
Zhe Xu,
Jinsheng Lin,
Linzhi He,
Gengjia Chen,
Ziwen Zheng,
Zhixing Xu,
Jingyan Chen,
Jiaming Guo,
Zhile Wu,
Ailing Duan,
Weizhan Luo,
Xinyu Song,
Shiyue Li

Affiliations

Junfeng Huang: 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
Shuojia Xie: 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
Yuewen Gao: 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
Zikai Lin: 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
Zhe Xu: 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
Jinsheng Lin: 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
Linzhi He: 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
Gengjia Chen: 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
Ziwen Zheng: 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
Zhixing Xu: 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
Jingyan Chen: 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
Jiaming Guo: 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
Zhile Wu: 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
Ailing Duan: 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
Weizhan Luo: 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
Xinyu Song: 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
Shiyue Li: 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

DOI: https://doi.org/10.1186/s13023-025-03617-3
Journal volume & issue: Vol. 20, no. 1
pp. 1 – 14

Abstract

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Abstract Background 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. Methods 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. Findings 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. Interpretation 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.

Published in Orphanet Journal of Rare Diseases

ISSN: 1750-1172 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine
Website: https://ojrd.biomedcentral.com

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