Pulmonary alveolar proteinosis
Pulmonary alveolar proteinosis | |
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Other names | alveolar proteinosis |
Micrograph of pulmonary alveolar proteinosis, showing the characteristic airspace filling with focally dense globs referred to as chatter or dense bodies. H&E stain. | |
Specialty | Pulmonology |
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by an abnormal accumulation of surfactant-derived lipoprotein compounds within the alveoli of the lung. The accumulated substances interfere with the normal gas exchange and expansion of the lungs, ultimately leading to difficulty breathing and a predisposition to developing lung infections. The causes of PAP may be grouped into primary (autoimmune PAP, hereditary PAP), secondary (multiple diseases), and congenital (multiple diseases, usually genetic) causes, although the most common cause is a primary autoimmune condition in an individual.
Signs and symptoms
The signs and symptoms of PAP include shortness of breath,[1] cough, low grade fever, and weight loss. Additionally, the clinical course of PAP is unpredictable. Spontaneous remission is recognized, and some patients have stable symptoms. Death may occur due to the progression of PAP or of any underlying associated disease. Individuals with PAP are more vulnerable to lung infections such as nocardiosis, Mycobacterium avium-intracellulare infection, or fungal infections.[1]
Causes
The abnormal accumulation of lipoproteinaceous compounds in PAP is due to impaired surfactant regulation and clearance. This is usually related to impaired alveolar macrophage function.
Secondary causes of PAP are those in which the accumulation of lipoproteinaceous compounds is secondary to another disease process. This has been recognized in the settings of certain cancers (such as myeloid leukemia), lung infections, or environmental exposure to dusts or chemicals, such as nickel.[3]
Although the cause of PAP was not originally understood, a major breakthrough in the understanding of the cause of the disease came by the chance observation that mice bred for experimental study to lack a hematologic
The implications of this finding are still being explored, but significant progress was reported in February 2007. Researchers in that report discussed the presence of anti-
Familial or sporadic
Genetics
Hereditary pulmonary alveolar proteinosis is a recessive genetic condition in which individuals are born with genetic mutations that deteriorate the function of the CSF2 receptor alpha on alveolar macrophages. 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.[8][9]
Diagnosis
The diagnosis of PAP is made using a combination of a person's symptoms, chest imaging, and microscopic evaluation of lung washing/tissue. Additional testing for serum anti-GM-CSF antibodies are helpful for confirmation.[10]
Although both the symptoms and imaging findings are stereotypical and well-described, they are non-specific and indistinguishable from many other conditions. For example,
Lung washings or tissue for histopathologic analysis are most commonly obtained using
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. There is typically a low numbers of macrophages and inflammatory cells (although this is variable).[13][14]
Treatment
The standard treatment for PAP is whole-lung
Epidemiology
The disease is more common in males and in tobacco smokers.[citation needed]
In a recent epidemiologic study from Japan,
History
PAP was first described in 1958[27] by the physicians Samuel Rosen, Benjamin Castleman, and Averill Liebow.[28] 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.[citation needed]
The reported treatment of PAP using therapeutic bronchoalveolar lavage was in 1960 by Dr. Jose Ramirez-Rivera at the Veterans' Administration Hospital in Baltimore,[29] who described repeated "segmental flooding" as a means of physically removing the accumulated alveolar material.[30]
Research
PAP is one of the rare lung diseases currently being studied by the Rare Lung Diseases Consortium. The consortium is part of the
References
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