# Retrospective Autoimmune PAP Natural History and Patient-Reported Outcomes Study

> **NIH FDA R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $300,000

## Abstract

ABSTRACT
Despite enormous advances in our understanding of autoimmune pulmonary alveolar proteinosis (aPAP), a rare disorder
of macrophage dysfunction, alveolar surfactant accumulation, and hypoxemic respiratory failure, no longitudinal studies
have defined its natural history, no clinical or patient-reported outcome measures have been validated in aPAP patients,
and no FDA-approved therapy is currently available. Currently, aPAP is treated by whole lung lavage, an invasive,
inefficient procedure requiring general anesthesia and mechanical ventilation that aims to physically remove the excess
surfactant by washing it out with up to 50 litters saline per lung. We elucidated the pathogenesis of aPAP, established an
accurate blood test for diagnosis now serving as the gold-standard, and participated in multiple clinical trials identifying
inhaled GM-CSF as a promising pharmacotherapy of aPAP. Notwithstanding, a poorly defined natural history (in terms of
disease progression) and lack of validated outcome measures are critical barriers to pharmacotherapeutic development.
The objective of this proposal is to use our existing US National PAP Registry to conduct a retrospective natural history
study of aPAP to define disease progression in terms of how patients, function, their treatment requirements and degree
of lung impairment; and to develop and test novel tools to measure and monitor changes in the severity of aPAP lung
disease. The central hypothesis is that defining the natural history of aPAP using an outcome measure incorporating how
patients feel, function, and breathe as a function of the severity of their lung disease and developing tools to measure
clinical outcomes will accelerate pharmacotherapeutic development for aPAP. The rationale for the proposed research is
that availability of information defining the natural history of aPAP and outcome measures reflecting how patients feel
and function (and quality of life) will accelerate pharmacotherapeutic development by providing more appropriate clinical
trial end points and knowledge how to interpret them. We plan to address this hypothesis in 3 Specific Aims: 1) conduct
of a retrospective, longitudinal, medical chart-based natural history study of aPAP; 2) develop and test a novel patient-
reported outcome measure - aPAP disease severity score (aPAP-DSS) that reflects how patients feel, function (and quality
of life), their requirement for supplemental oxygen therapy, and an objective measure of impairment in gas exchange (the
diffusing capacity of the lungs for carbon dioxide (DLCO%); 3) develop and test a novel patient-reported outcome measure
of aPAP disease severity (5-minute step test) better able to elicit/demonstrate the impairment in oxygen delivery than the
six-minute walk test. The proposed research is innovative because it represents a marked departure from existing
approaches (e.g., cross-sectional studies and use of clinical trial end points not validated in aPAP that don’t ref...

## Key facts

- **NIH application ID:** 10571074
- **Project number:** 1R01FD007604-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Bruce C Trapnell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10571074

## Citation

> US National Institutes of Health, RePORTER application 10571074, Retrospective Autoimmune PAP Natural History and Patient-Reported Outcomes Study (1R01FD007604-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10571074. Licensed CC0.

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