The Longitudinal Evaluation of Autoimmune Pulmonary Alveolar Proteinosis

PAP is a rare syndrome of surfactant accumulation and resulting hypoxemic respiratory failure
that occurs in a number of diseases classified pathogenically into three groups: primary PAP
(caused by disruption of GM-CSF signaling - autoimmune PAP, hereditary PAP), secondary PAP
(caused by reduction in alveolar macrophage numbers and/or functions), and surfactant
dysfunction-related PAP (caused by mutations in genes required for normal surfactant
production). In current clinical practice, PAP is diagnosed based on a lung biopsy; an
approach that is not able to identify the PAP-causing disease in anyone. Current therapy
involves the physical removal of surfactant by a procedure in which the lungs are repeatedly
filled with saline and emptied - whole lung lavage, which is invasive, inefficient, and not
widely available, especially for children. Importantly, research advances have elucidated the
pathogenesis of diseases causing PAP in most patients and have identified new diagnostic and
therapeutic approaches. Simple blood-based research tests can now identify the PAP-causing
disease in about 95% of patients. Further, several promising potential disease-specific
therapies are currently in development. The long-term goals of the Rare Lung Diseases
Consortium include improving the diagnosis and therapy of people with PAP. A major goal of
this protocol is to conduct a prospective, longitudinal study of autoimmune PAP to examine
outcome measures for disease severity for potential use in clinical practice and/or clinical
research studies. The investigator's central hypothesis is that a prospective, longitudinal
study of autoimmune PAP patients will facilitate the identification of useful outcome
measures for use in clinical practice and/or clinical research studies. The specific
objectives of the study are to: 1) evaluate blood-based biomarkers of PAP lung disease over
time in autoimmune PAP patients, 2) evaluate the natural history/clinical course of
autoimmune PAP over time, 3) evaluate quality of life measures over time in autoimmune PAP
patients, 4) evaluate physiologic measures of disease over time in autoimmune PAP patients,
and 5) evaluate radiologic measures of lung disease progression over time in autoimmune PAP
patients. The study design will be observational and will involve recruitment, screening, and
enrollment of eligible participants and annual collection of clinical data. The experimental
approach will be to assess the rate of change in GM-CSF signaling assay parameters from
baseline to 24 months. GM-CSF signaling assay parameters include GM-CSF autoantibody (GMAb)
level, pSTAT5-Max, STAT5-phosphorylation index (STAT5-PI), GM-CSF signaling index (GM-SI),
and GM-CSF EC50. The study will also assess the progression of autoimmune PAP, including but
not limited to use of treatment options, the number and types of infections and other
inter-current medical issues with quality of life measures, exercise tolerance, and
radiologic imaging. Experimental outcomes will evaluate SP-D, cholestenoic acid, and lipid
levels. Anticipated results will establish a natural history/clinical course of autoimmune
PAP to better serve patients and providers, to better inform PAP researchers, and validate
outcome measures and biomarkers for use in future clinical studies of PAP. These results will
impact the field by: 1) improving an understanding of the clinical course of autoimmune PAP,
2) providing information on various clinical outcome and quality of life outcome measures to
guide patients and physicians in making treatment choices, and 3) facilitate the development
of pharmacotherapeutics for autoimmune PAP and 4) better informing PAP researchers.

Inclusion Criteria:

- Written informed consent must be provided by:

- Participant if at least 18 years old -OR-

- Parent/legal guardian if participant is less than 18 years old -AND-

- Participant provides assent when appropriate

- History of diagnosis of autoimmune as indicated by a:

- History of chest CT or x-ray findings compatible with PAP -AND-

- History of a Positive (Abnormal) serum GMAb test

Exclusion Criteria:

- Individuals who have a serious medical illness that, in the opinion of the
investigator, is likely to interfere with completion of the study will be excluded.