Pulmonary Alveolar Proteinosis (PAP) is a not a single disease – it is a rare syndrome or condition that can occur in several different diseases. The syndrome is caused by the buildup of surfactant in the lungs that makes breathing difficult. Normally, surfactant is present as a very thin layer on the lung surface. It helps keep the millions of tiny air sacs (alveoli) stay open as we breath. The thin layer of surfactant is maintained by balanced production and destruction inside alveoli. Alveolar macrophages are special cells inside alveoli that remove excess surfactant from alveoli. This helps keep the surfactant layer thin and useful. Macrophages require stimulation by a protein called GM-CSF in order to function correctly and remove surfactant. PAP occurs when something happens that disturbs the balance of surfactant production and removal. When this occurs, surfactant builds up inside the alveoli over time. Eventually, the alveoli fill up completely with surfactant leaving no room for the air we breathe to enter. The result is that oxygen can’t get into the blood as easily, which causes a feeling of breathlessness.
The different diseases in which PAP occur can be divided into three groups: Primary PAP, Secondary PAP, and Disorders of surfactant Metabolism.
- Primary PAP occurs when something prevents GM-CSF from stimulating alveolar macrophages. This reduces their ability to remove excess surfactant and causes PAP. There are two diseases in this group autoimmune PAP and hereditary PAP.
- Autoimmune PAP (aPAP) is a disease that develops when a person’s immune system begins making proteins that attack GM-CSF. These proteins are called GM-CSF autoantibodies and large amounts of them prevent GM-CSF from helping alveolar macrophages remove excess surfactant. This results in surfactant accumulation and the development of PAP. Autoimmune PAP occurs mostly in adults but can occur in young children
- Hereditary PAP (hPAP) is a genetic disease that causes GM-CSF to not be recognized by alveolar macrophages. This prevents GM-CSF from helping alveolar macrophages remove excess surfactant. This results in surfactant accumulation and the development of PAP. Normally, GM-CSF is recognized by proteins on the surface of alveolar macrophages (and other cells) called GM-CSF receptors. Similar to the way a key fits into and turns a lock to open it, GM-CSF fits into these surface proteins and ‘opens’ or, rather, activates them. This causes alveolar macrophages to be able to remove excess surfactant. In hPAP, mutations occur in the genes that serve as blueprints for making GM-CSF receptors. The result is that when the blueprint containing ‘bad’ instructions is used, the GM-CSF receptors are abnormal and don’t recognize GM-CSF. Some mutations are so severe that the GM-CSF receptors aren’t even made. Hereditary PAP occurs mostly in children but can occur in adults.
- Secondary PAP (sPAP) occurs when something reduces either the number of alveolar macrophages or reduces their ability to function to remove surfactant. In either case, there are less alveolar macrophages inside alveoli to remove excess surfactant. This results in surfactant accumulation and the development of PAP. Secondary PAP can occur in diseases that affect the formation of blood cells. It can also occur after breathing in toxic dusts. Secondary PAP is more common in adults but can occur in children.
- Disorders of surfactant production (DSP) are genetic diseases that cause abnormalities in proteins needed to make surfactant. This results in the production of abnormal surfactant. The disease that occurs depends on which gene is affected and exactly what mutation is present. Some mutations result in death in the first hour of life and some slowly scar the lungs over time and appear in children, adolescents, or adults.
PAP has the following symptoms:
- Shortness of breath, also called dyspnea
- Chest pain or tightness
- Fever
- Weight loss
- Cough (sometimes, but not always)
- Low levels of oxygen in the blood
- Nail clubbing (abnormal growth of toenails or fingernails)
The mainstay of PAP treatment for a very long time has been therapeutic whole-lung lavage (WLL). This procedure involves cleaning out one lung at a time with saline while the other lung is fed with oxygen. During the procedure, you wear an agitating (vibrating) vest around your chest. As liters of saline flush through your lung through special tubing, the agitation from the vest plus the saline liquid causes your airways to release the breath-clogging surfactant. Another tube positioned in your lung suctions the liquid out of your body. This "lung power-washing" procedure is performed under general anesthesia and usually takes from two to five hours to complete. Pulmonary Alveolar Proteinosis (PAP) is not a common disease, but it is serious and deadly. Always take care of yourself eat right, be physically active, take care of your lungs, and have a positive outlook in life!
ZS DMO II Karla P. Calapardo, RND
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