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Pulmonary alveolar proteinosis (PAP)

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PAP is a rare syndrome (a pattern of symptoms and signs) characterized by abnormal accumulation of surfactant-like material in the air sacs of the lungs causing impairment of gas exchange.

Causes of PAP

PAP occurs in three distinct forms:

Primary PAP, includes autoimmune (most common form) and hereditary PAP

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates clearance of surfactant in the lungs. In autoimmune PAP, the body’s immune cells begin making GM-CSF autoantibody that blocks GM-CSF activity resulting in abnormal clearance of surfactant. In hereditary PAP, individuals are born with gene mutations that cause GM-CSF receptor dysfunction.

Secondary PAP

This can develop in association with some hematologic cancers, pharmacologic immunosuppression, and chemotherapy, inhalation of organic dusts (e.g. silica, titanium) or toxic fumes, and infections.

Congenital PAP

This is caused by genetic mutations that disrupt the production of normal surfactant.

PAP symptoms

  • Shortness of breath
  • Cough
  • Fatigue and malaise
  • Low-grade fever
  • Chest pain

PAP diagnosis and tests

  • Chest X-ray is the first step in evaluation. It may show diffuse or multifocal lung opacities.
  • High-resolution CT scans can show a characteristic pattern of hazy white shadows and angular lines (crazy-paving appearance)
  • Blood tests include specific tests that identify the presence or absence of GM-CSF autoantibody in autoimmune PAP or genetic testings in hereditary or congenital PAP
  • Pulmonary function test
  • Bronchoscopy with lung washings can be examined to demonstrate PAP is present
  • Lung biopsy, used in case of insufficient evidence

PAP treatment

  • Spontaneous resolution may occur, but intervention is required in the majority of patients and the options of treatment depend on the form of diseases.
  • Treatment of any underlying causes
  • The current standard therapy is whole lung lavage, which is a procedure for removing lipoproteinaceous material from the lungs. It can be effective in primary PAP and some diseases in secondary PAP.
  • Investigational therapies (e.g. GM-CSF administration)
  • Lung transplantation

Additional resources for PAP patients

When to contact your doctor about PAP

You need to be evaluated right away to determine the cause of your symptoms. If you're concerned that you or a loved one may have PAP, please get in touch with your physician to find out what would be the appropriate treatment.