Outcomes and outcome measures in studies of pulmonary alveolar proteinosis: a scoping review

Background
Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by progressive accumulation of surfactant-derived lipoproteinaceous material within alveoli, impairing gas exchange and causing respiratory insufficiency. Despite therapeutic advances such as whole lung lavage, substantial heterogeneity persists in outcome selection and reporting across studies, limiting comparability and evidence synthesis.

Objective
To systematically map and categorise outcomes and outcome measures reported in studies of PAP treatments and establish a foundation for developing a standardised core outcome set (COS).

Methods
A scoping review was conducted across four databases and two clinical trial registries (May 2024, updated May 2025). Eligible studies included those reporting treatment outcomes in patients of any age with PAP. Outcomes and measures were extracted and categorised using the Core Outcome Measures in Effectiveness Trials taxonomy.

Results
From 8475 screened records, 62 studies met the inclusion criteria, encompassing 31 distinct outcomes and 92 corresponding outcome measures. Physiological parameters dominated reporting, including arterial oxygenation (n=55, 89%; such as arterial oxygen tension and alveolar–arterial oxygen gradient) and lung function indices (n=53, 85%; such as diffusing capacity of the lung for carbon monoxide and forced vital capacity) were most frequently assessed. In contrast, patient-centred outcomes such as quality of life were reported in only 10 (16%) studies, while adverse events were relatively well-reported (n=41, 66%).

Conclusions
The reporting of outcomes and outcome measures in PAP studies is highly variable. There is an urgent need for a COS tailored to PAP that focuses on physiological outcomes, adverse events and patient-reported outcomes.


Aim

To provide information for the development of a COS for PAP by reviewing the published literature to summarize the outcomes reported in pulmonary alveolar proteinosis and how they are measured.


Contributors

Jin Xiong, Ruobing Lei, Guangli Zhang, Xiaoyin Tian, Ruixue Gu, Yaolong Chen, Zhengxiu Luo

Publication

Journal: Eur Respir Rev
Volume: 35
Issue: 179
Pages: 250154 -
Year: 2026
DOI: 10.1183/16000617.0154-2025

Further Study Information

Current Stage: Completed
Date: April 2024 - October 2024
Funding source(s): None


Health Area

Disease Category: Lungs & airways

Disease Name: Pulmonary Alveolar Proteinosis

Target Population

Age Range: 0 - 100

Sex: Either

Nature of Intervention: Any

Stakeholders Involved

- None

Study Type

- Systematic review of outcomes measured in trials

Method(s)

- Systematic review

A systematic review was conducted according to PRISMA-ScR. We searched the electronic databases MEDLINE, Embase, Cochrane, and Web of science for studies published from inception to April 2024 using the keywords "Pulmonary Alveolar Proteinosis" and "lung Alveolar Proteinosis". Registered, unpublished trials in Clinical trial.gov and ICTRP were also included.