What Is Pulmonary Alveolar Proteinosis (PAP)?
Some diseases do not take away the ability to breathe—they quietly block breathing itself.
Pulmonary Alveolar Proteinosis (PAP) is a rare lung disease. In people with PAP, the lungs do not lose their function outright; instead, they are gradually filled with substances that should not be there. These lipid- and protein-rich materials accumulate within the alveoli, forming an invisible haze that interferes with the most critical exchange between air and blood. Over time, this disruption leads to progressive difficulty in breathing.
Why Do the Lungs Become “Filled”?
We often imagine the lungs as simple “air sacs,” but in reality, they resemble a finely structured forest of sponges composed of countless alveoli. These tiny air sacs allow oxygen from the air to enter the bloodstream while removing carbon dioxide.
The walls of the alveoli are extremely thin. To keep them open and functional, they are coated with a layer of oily, protein-based material known as pulmonary surfactant. Under normal conditions, excess surfactant is continuously cleared by specialized immune cells in the lungs called alveolar macrophages, preventing it from accumulating and obstructing the alveoli.
In patients with Pulmonary Alveolar Proteinosis, this clearance system fails. A critical signaling pathway becomes disrupted, leaving alveolar macrophages unable to remove the excess surfactant. As a result, these materials gradually build up, filling the alveoli—silently and insidiously—without obvious inflammation or pain to serve as a warning sign (Figure 1).
Figure 1. Pathogenesis of Pulmonary Alveolar Proteinosis
Figure 2. Chest CT scan of a patient with Pulmonary Alveolar Proteinosis
How Does the Disease Gradually Reveal Itself?
The onset of the disease is often not dramatic. In its early stages, patients may simply notice shortness of breath more easily, reduced exercise tolerance, and a mild cough.
These symptoms are easily mistaken for fatigue, infection, or poor physical fitness. As the abnormal material continues to accumulate, the amount of alveolar space truly available for gas exchange steadily decreases. Breathing becomes increasingly labored, blood oxygen levels fall, and a bluish discoloration of the skin and lips (cyanosis) may appear. In severe cases, patients may feel that “there is not enough air,” even while sitting still.
Under normal conditions, the alveoli continuously produce a substance known as pulmonary surfactant. This material is essential for normal breathing, but when present in excess, it must be promptly cleared. The primary role of alveolar macrophages is to remove this excess surfactant, while also clearing debris and pathogens that enter the alveoli, thereby keeping the air spaces open and functional.
In Pulmonary Alveolar Proteinosis, the problem does not lie in a reduced number of alveolar macrophages, but rather in the suppression of their function. In most patients, an abnormal immune response leads to the production of antibodies against GM-CSF (granulocyte–macrophage colony-stimulating factor).
GM-CSF is a signaling molecule essential for the normal maturation and function of alveolar macrophages. When GM-CSF signaling is blocked by these antibodies, alveolar macrophages fail to mature properly, resulting in a marked reduction in their ability to clear pulmonary surfactant. Consequently, proteinaceous material gradually accumulates within the alveoli (Figure 2). Over time, these deposits impair normal oxygen exchange, leading to symptoms such as shortness of breath and reduced exercise tolerance.
How Does This Disease Affect Daily Life?
Pulmonary Alveolar Proteinosis affects more than just the lungs. Prolonged oxygen deprivation can lead to persistent fatigue, limited physical activity, and poor sleep quality at night. Repeated medical examinations, abnormal imaging findings, and the uncertainty surrounding the disease can also place a significant psychological burden on patients.
For some individuals, the most difficult aspect is not pain, but the gradual realization that breathing itself has become something that requires constant attention.
What Can Modern Medicine Do?
Pulmonary Alveolar Proteinosis is not without intervention. Currently, the most established and effective treatment is whole lung lavage. Under general anesthesia, large volumes of saline are repeatedly used to wash the lungs, removing the accumulated material and restoring open air spaces, as shown in Figure 3.
However, because whole lung lavage does not address the underlying dysfunction of alveolar macrophages, the procedure often needs to be repeated at intervals of months or even years, depending on the severity of the disease.
For some patients with autoimmune-related forms of the condition, physicians may also consider therapies aimed at modulating immune signaling and rebuilding the lung’s natural clearance system. Meanwhile, ongoing research continues to explore ways to restore the lung’s intrinsic capacity for self-repair at its source.
Figure 3. Whole Lung Lavage