Evidence map›Paper›PMID 40038784›Full record

ArticleOrphanet journal of rare diseases2025

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 and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Outcomes and outcome measures in studies of pulmonary alveolar proteinosis: a scoping review.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

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, Guangzhou, Guangdong, China.
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, Guangzhou, Guangdong, China.
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, Guangzhou, Guangdong, China.
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, Guangzhou, Guangdong, China.
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, Guangzhou, Guangdong, China.
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, Guangzhou, Guangdong, China.
Linzhi HeGuangzhou 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.
Gengjia ChenGuangzhou 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.
Ziwen ZhengGuangzhou 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.
Zhixing XuGuangzhou 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.
Jingyan ChenGuangzhou 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.
Jiaming GuoGuangzhou 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.
Zhile WuGuangzhou 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.
Ailing DuanGuangzhou 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.
Weizhan LuoGuangzhou 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.
Xinyu SongGuangzhou 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. songxinyu@gzhmu.edu.cn.
Shiyue LiGuangzhou 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. lishiyue@gird.cn.

Funding

Guangdong Fundamental and Basic Fundamental Project 2024A1515011593Guangdong Science and Technology Project 2021A050520012Guangzhou Fundamental and Basic Fundamental Projects 2023A04J0573Guangzhou Joint Projects of University 2024A03J1143Incubation Program of National Science Foundation for Distinguished Young Scholars GMU2020-207Innovation team of respiratory diseases and regenerative medicine 2021KCXTD028the Clinical and Epidemiological Research Projects of State Key Laboratory of Respiratory Disease SKLRD-L-202502the National Natural Science Foundation of China 81870079the National Nature Science Foundation of China 82202222Young Talent Support Project of Guangzhou Association for Science and Technology QT-2024-038Zhongnanshan medical foundation of Guangdong Province ZNSA-2020013
6 · The paper itself

Abstract

backgroundPulmonary 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.

methodsThe 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.

findingsOur 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.

interpretationThis 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.

Indexed as

Pulmonary Alveolar ProteinosisAdultAgedFemaleHumansMaleMiddle AgedPhenotypePrognosisGeneticsPhenotypic heterogeneityPrognosisPulmonary alveolar proteinosis

Identifiers

PMID40038784
PMCPMC11881271

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