A National Registry For 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 establish a National PAP Registry. Our central hypothesis is that a
nationwide campaign to enroll and communicate with a large cohort of PAP patients will have
important benefits including 1) accelerating the translation of research diagnostics into
clinical practice, 2) increasing knowledge among patient and healthcare communities about
PAP, and 3) engagement of PAP patients and doctors in planning and conducting PAP research.
The specific objectives of this study are to: 1) determine the ability of the DBSC GMAb Test
to correctly identify autoimmune PAP among people with PAP of any type, 2) estimate the
prevalence of autoimmune PAP, 3) increase communication and knowledge about PAP-causing
diseases, PAP research advances, and future research studies among PAP patients, healthcare
providers, the medical community, the PAP Foundation, the Translational Pulmonary Science
Center (TPSC) and the general public, 4) evaluate the ability of DBSC-based test to correctly
identify genetic factors that increase the risk of developing PAP; and 5) to evaluate the
ability of the DBSC GMAb Test to correctly identify autoimmune PAP among people with PAP of
any type, or another lung diseases, and healthy controls. The target population is any person
diagnosed with PAP. The study design will involve recruitment, screening, and enrollment of
Participants via short telephone-based study visits, completion of questionnaires, and
collection of capillary blood from the fingertip by Participants in their home using a DBSC,
which are then sent by US mail to the TPSC for evaluation. The experimental approach will
compare GMAb levels from DBSCs from Participants diagnosed with PAP and determine the
fraction of autoimmune PAP patients among individuals with PAP. DBSC-based genetic testing
will be compared to current blood-based methods for identification of known genetic risk
factors for developing PAP. Lastly, DBSC GMAb values will be compared to GMAb values from
healthy and lung disease controls to determine the ability of the DBSC GMAb test to identify
patients with autoimmune PAP. Anticipated results will establish a National PAP registry,
validate tests for diagnosis of diseases causing PAP in more than 90% of patients, increase
awareness and understanding of PAP among patients and healthcare providers, and provide for a
patient voice in PAP research. These results will impact the field by: 1) transforming how
PAP is diagnosed, 2) increasing access to diagnostic testing - of special importance to those
in remote locations, and 3) engaging PAP patient and healthcare communities in planning and
implementing PAP research including a prospective natural history study and clinical trials
evaluating several potential, disease-specific therapies.

Inclusion Criteria:

- Written informed consent and assent if necessary

- History of chest computed tomogram or chest radiograph findings compatible with PAP

- History of diagnosis of PAP made by at least one of the following methods:

- Positive (Abnormal) serum GMAb test -OR-

- Lung biopsy clearly documenting the presence of PAP of any type or degree -OR-

- Bronchoalveolar lavage cytology compatible with PAP -OR-

- Recessive or compound mutations in genes known to cause PAP, i.e. GM-CSF receptor
α or β chain, GM-CSF, surfactant protein B or C or ABCA3, ABCG1, ABCA1, TTF1

Exclusion Criteria:

- Individuals that do not have a diagnosis of PAP

- 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.