Pulmonary alveolar proteinosis
Encyclopedia
Pulmonary alveolar proteinosis (PAP) is a rare lung
disease
in which abnormal accumulation of surfactant
occurs within the alveoli, interfering with gas exchange
. PAP can occur in a primary form or secondarily in the settings of malignancy (especially in myeloid leukemia
), pulmonary infection, or environmental exposure to dusts or chemicals. Rare familial forms have also been recognized, suggesting a genetic
component in some cases.
The clinical course of PAP is unpredictable. Spontaneous remission is recognized; some patients have stable symptoms. Death may occur due to progression of PAP or due to the underlying disease associated with PAP. Individuals with PAP are more vulnerable to infection of the lung
by bacteria or fungi.
known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome
of abnormal surfactant accumulation resembling human PAP.
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-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice.
s of affected individuals typically reveal nonspecific alveolar opacities. Diagnosis
is generally made by surgical or endoscopic biopsy
of the lung, revealing the distinctive pathologic finding. The current gold standard of PAP diagnosis
involves histopathological examination of alveolar specimens obtained from bronchoalveolar lavage and transbronchial lung biopsy.
On histopathological examination distal air spaces are filled with a granular, eosinophillic material that stain positively with PAS reagent and is diastase resistant.
The standard treatment for PAP is whole-lung lavage
, in which sterile fluid is instilled into the lung and then removed, along with the abnormal surfactant material. This is generally effective at ameliorating symptoms, often for prolonged periods. Since the mouse discovery noted above, the use of GM-CSF injections has also been attempted, with variable success. Lung transplantation
can be performed in refractory cases.
smokers.
In a recent epidemiologic study from Japan, Autoimmune PAP has an incidence and prevalence higher than previously reported and is not strongly linked to smoking, occupational exposure, or other illnesses.
rich material was subsequently recognized to be surfactant.
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
in which abnormal accumulation of surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...
occurs within the alveoli, interfering with gas exchange
Gas exchange
Gas exchange is a process in biology where gases contained in an organism and atmosphere transfer or exchange. In human gas-exchange, gases contained in the blood of human bodies exchange with gases contained in the atmosphere. Human gas-exchange occurs in the lungs...
. PAP can occur in a primary form or secondarily in the settings of malignancy (especially in myeloid leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
), pulmonary infection, or environmental exposure to dusts or chemicals. Rare familial forms have also been recognized, suggesting a genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
component in some cases.
Signs and symptoms
The symptoms of PAP include:- dyspneaDyspneaDyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
(shortness of breath) - coughCoughA cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
- low grade feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
- weight loss
The clinical course of PAP is unpredictable. Spontaneous remission is recognized; some patients have stable symptoms. Death may occur due to progression of PAP or due to the underlying disease associated with PAP. Individuals with PAP are more vulnerable to infection of the lung
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
by bacteria or fungi.
Mechanism
Although the cause of PAP remains obscure, a major breakthrough in the understanding of the etiology of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factorGrowth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
of abnormal surfactant accumulation resembling human PAP.
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-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice.
Diagnosis
Chest x-rayX-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s of affected individuals typically reveal nonspecific alveolar opacities. Diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
is generally made by surgical or endoscopic biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the lung, revealing the distinctive pathologic finding. The current gold standard of PAP diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
involves histopathological examination of alveolar specimens obtained from bronchoalveolar lavage and transbronchial lung biopsy.
On histopathological examination distal air spaces are filled with a granular, eosinophillic material that stain positively with PAS reagent and is diastase resistant.
Treatment
The first advance in the treatment of Pulmonary Alveolar Proteinosis came in November 1960, when Dr. Jose Ramirez-Rivera at the Veterans' Administration Hospital in Baltimore applied repeated "segmental flooding" as a means of physically removing the accumulated alveolar material.The standard treatment for PAP is whole-lung lavage
Lavage
In medicine, therapeutic irrigation or lavage is a general term referring to cleaning or rinsing.Specific types include:* Antiseptic lavage* Bronchoalveolar lavage* Gastric lavage* Peritoneal lavage* Arthroscopic lavage* Ductal lavage...
, in which sterile fluid is instilled into the lung and then removed, along with the abnormal surfactant material. This is generally effective at ameliorating symptoms, often for prolonged periods. Since the mouse discovery noted above, the use of GM-CSF injections has also been attempted, with variable success. Lung transplantation
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
can be performed in refractory cases.
Epidemiology
The disease is more common in males and in tobaccoTobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
smokers.
In a recent epidemiologic study from Japan, Autoimmune PAP has an incidence and prevalence higher than previously reported and is not strongly linked to smoking, occupational exposure, or other illnesses.
History
PAP was first described in 1958 by the physicians Samuel Rosen, Benjamin Castleman, and Averill Liebow. 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 lipidLipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
rich material was subsequently recognized to be surfactant.