Consequently, a messenger molecule known as granulocyte/macrophage-colony stimulating factor (GM-CSF) is unable to stimulate alveolar macrophages to clear surfactant, leading to difficulty with breathing. The gene for the CSF2 receptor alpha is located in the 5q31 region of chromosome 5, and the gene product can also be referred to as granulocyte macrophage colony-stimulating factor receptor. Diagnosis
The diagnosis of PAP is made using a combination of a persons symptoms, chest imaging, and microscopic evaluation of lung washing/tissue. Additional testing for serum anti-GM-CSF antibodies are helpful for confirmation.Although both the symptoms and imaging findings are stereotypical and well-described, they are non-specific and indistinguishable from many other conditions. For example, chest x-ray may show alveolar opacities, and a CT may show a crazy paving lung pattern, both of which are seen more commonly in numerous other conditions. Thus, the diagnosis primarily depends on the pathology findings.Lung washings or tissue for histopathologic analysis are most commonly obtained using bronchoalveolar lavage and/or lung biopsy. Characteristic biopsy findings show filling of the alveoli (and sometimes terminal bronchioles) with an amorphous eosinophilic material, which stains strongly positive on PAS stain and the PAS diastase stain. The surrounding alveoli and pulmonary interstitium remain relatively normal. Electron microscopy of the sample, although not typically performed due to impracticality, shows lamellated bodies representing surfactant. An alternative diagnosis with similar histomorphologic findings is Pneumocystis jirovicii pneumonia.Lung washings characteristically yield a fluid which is "milky"composition. Under the microscope, samples show 20-50 micrometer PAS-positive globules on a background of finely granular or amorphous PAS-positive material.
In their case series published in the New England Journal of Medicine on June 7 of that year, they described 27 patients with pathologic evidence of periodic acid Schiff positive material filling the alveoli. This lipid rich material was subsequently recognized to be surfactant.The reported treatment of PAP using therapeutic bronchoalveolar lavage was in 1960 by Dr. Jose Ramirez-Rivera at the Veterans Administration Hospital in Baltimore, who described repeated "segmental flooding" as a means of physically removing the accumulated alveolar material. Research
PAP is one of the rare lung diseases currently being studied by the Rare Lung Diseases Consortium. The consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, of the National Center for Advancing Translational Sciences, and dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the National Institutes of Health, patient organizations and clinical investigators. References
External links
ORPHANET/ The portal for rare diseases and orphan drugs