Healthy lungs contain a small amount of this surfactant, which normally helps the lungs expand during breathing. In healthy individuals, there is constant production and degradation of surfactant, which maintains a small amount of surfactant lining the lungs. A cell in the lungs called the macrophage is responsible for degrading the surfactant. In PAP (Pulmonary Alveolar Proteinosis), the macrophage’s ability to degrade surfactant is impaired, resulting in abnormal and excessive accumulation of surfactant within the airspaces of the lungs. In healthy lungs, the macrophages receive a signal from a protein called GM-CSF signaling them to clear surfactant. The macrophages recognize the GM-CSF by a sensor on the surface of the cell called the GM-CSF receptor.
There are three types of PAP: Autoimmune, Hereditary, and Secondary, which vary in the cause of the macrophage’s ability to clear surfactant.
In autoimmune PAP, the immune system produces antibodies that attack GM-CSF, preventing this signal from telling the macrophage to clear surfactant. This results in abnormal and excessive accumulation of surfactant in the lungs. Ninety percent of patients diagnosed with PAP have autoimmune PAP.
Rare individuals have a genetic mutation in the GM-CSF receptor, resulting in the maccrophage’s inability to sense the GM-CSF signal to clear surfactant. Hereditary PAP is usually diagnosed during childhood and accounts for approximately 5% of cases of PAP.
Secondary PAP often results from impaired macrophage function due to blood cancers but can also be associated with other cancers, immunodeficiency syndromes such as AIDS, and inhalation of dusts or fumes.
PAP is a rare condition, occurring in approximately 7-10 per million individuals. The average age of diagnosis is 39. PAP can affect anyone but is more common in males and in smokers.
Pulmonary Alveolar Proteinosis Symptoms
Patients with mild disease may have no symptoms. In more severe cases, patients can experience shortness of breath, cough, and fatigue. PAP patients are susceptible to particular infections, so any fever should be reported immediately.