Pulmonary alveolar proteinosis is a rare disorder in which the air sacs of the lungs (alveoli) become plugged with a protein-rich fluid.
The cause of pulmonary alveolar proteinosis is almost always unknown, but recent studies have linked it to production of an antibody directed against a protein that seems to be involved with the production or the breakdown of surfactant (a substance normally produced in the lungs). Occasionally, development of pulmonary alveolar proteinosis is related to exposure to toxic substances, such as inorganic dusts, infection with Pneumocystis jirovecii (see Aspiration Pneumonia), certain cancers, and immunosuppressants. Rarely, it occurs in newborns.
The protein in the lungs plugs up the alveoli and small airways. In rare instances, lung tissue becomes scarred. The disease may progress, remain stable, or disappear spontaneously.
When the alveoli are plugged, the transfer of oxygen to the blood from the lungs is severely impaired. Consequently, most people with pulmonary alveolar proteinosis experience shortness of breath when they exert themselves. Some people have severe difficulty breathing, even at rest. Other symptoms may include fatigue, weight loss, and low-grade fever. Most people also have a cough that often does not produce sputum, but occasionally people expectorate chunky gelatinous material. People often have severe disability from inadequate lung function. Lung infections may quickly worsen symptoms of shortness of breath and produce fever.
A chest x-ray shows evidence of plugging of the alveoli. Computed tomography (CT) shows this plugging and other changes that suggest the disease. Pulmonary function tests (see Pulmonary Function Testing (PFT)) reveal that the volume of air that the lungs can hold is abnormally small. Tests show low levels of oxygen in the blood, at first only during exercise but later also when the person is at rest. The elimination of carbon dioxide from the lungs may be impaired. Blood test results are not specific for the diagnosis, although levels of some substances (for example, lactic dehydrogenase, red blood cells, serum surfactant proteins, and gamma globulin) are often elevated.
To make a definitive diagnosis, doctors examine a sample of the fluid from the alveoli. To obtain a sample, doctors use a bronchoscope (see Bronchoscopy) to wash segments of the lung with a salt-water solution and then collect the washings (bronchoalveolar lavage). The washings are often opaque or milky because the fluid is rich in protein and fats. Sometimes doctors obtain a lung tissue sample for microscopic examination (lung biopsy) during bronchoscopy. Occasionally, a larger sample is needed, which must be removed surgically.
People who have few or no symptoms do not require treatment. For people with disabling symptoms, the protein- and fat-rich fluid in the alveoli can be washed out with a salt solution during bronchoscopy or through a special tube inserted through the mouth or through the windpipe (trachea) and into one lung. Sometimes only a small section of the lung must be washed, but if symptoms are severe and the levels of oxygen in the blood are very low, the person is given general anesthesia, so that one entire lung can be washed. About 3 to 5 days later, the other lung is washed, again after the person has been given general anesthesia. One washing is enough for some people, but others need washings every 6 to 12 months for many years. Recombinant granulocyte-macrophage colony stimulating factor, a substance that stimulates the body's production of white blood cells, is being studied as a treatment.
Corticosteroids, such as prednisone, are not effective and may actually increase the chance of infection. Bacterial infections are treated with antibiotics, usually taken by mouth.
Some people with pulmonary alveolar proteinosis are short of breath indefinitely, but the disease is rarely fatal as long as they have regular lung washings.
Last full review/revision October 2013 by Harold R. Collard, MD