COMMON QUESTIONS

Useful Information

Find answers to some of the questions you may have regarding PAP & The PAP Foundation here. We’ve addressed some of the most common ones below, but if something isn’t clear feel free to contact us. We’ll be happy to assist you in any way possible.

What is PAP?

Pulmonary alveolar proteinosis (PAP) is not a single disease. It is a syndrome (a pattern of symptoms and signs) that occurs in multiple diseases that are each quite rare. Altogether, these diseases cause PAP in about 7 out of every one million people.

PAP occurs when surfactant builds up in the tiny air sacs (alveoli) of the lungs. Surfactant is normally present in small amounts and help alveoli stay open. In PAP, surfactant build-up blocks the air we breath from entering alveoli. This prevents oxygen from passing through into the blood and causes a feeling of breathlessness that worsens over time.

Causes of PAP

Multiple diseases cause PAP in men, women & children of all ages. These diseases can be usefully classified into the following groups:

Primary PAP. Diseases in this group are caused by loss of signaling to cells normally mediated by a protein called GM-CSF. Lung cells called alveolar macrophages need GM-CSF to prevent surfactant build up.
Autoimmune PAP is the most common disease in this group. It is also the most common of all PAP-causing diseases and accounts for about 85% to 90% of all people who develop PAP.
Hereditary PAP due to GM-CSF receptor dysfunction is less-common. It accounts for about 5% of people with PAP.
Secondary PAP. The many diseases in this group cause PAP by reducing alveolar macrophage numbers or functions, which leads to surfactant build up in alveoli. They account for about 5% of people with PAP.
Congenital PAP. Multiple diseases in this group are caused by mutations in genes required to produce normal surfactant. They account for about 5% of people with PAP.

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Symptoms of PAP

Common Symptoms and Signs

Breathlessness (feeling short of breath) – At first, this occurs only with activity but over time it also occurs while resting.
Cough
Low blood oxygen level – Measured as a reduced % oxygen saturation level using a fingertip pulse-oximeter.

Radiological Findings

‘Crazy paving’ on the chest CT scan – This pattern of hazy white shadows (referred to as ground glass opacities) and angular lines is characteristic – but not diagnostic – of PAP.

Current Treatment Options

Treatment options for PAP vary by disease because therapeutic effectiveness is related to the underlying mechanism of disease. Therapy that is effective for one PAP-causing disease may not work for a different disease.

Whole lung lavage (WLL) therapy is a medical procedure done under general anesthesia in which excess surfactant is ‘washed’ out of one lung with salt water (saline) while the other is connected to a breathing machine supplying oxygen. WLL can be effective in Primary PAP and in some diseases in the Secondary PAP group but is not effective in Congenital PAP. Lung transplantation has been used to treat PAP but does not prevent disease recurrence in autoimmune PAP.

Consequently, to determine what therapy may be appropriate for a patient and to consider the expected outcome, it is necessary to know which disease is causing PAP in that patient.

Treatments On The Horizon

GM-CSF augmentation. In development for autoimmune PAP – promising results.
Pivotal human trials are underway!
Immunomodulation. Has been tried in autoimmune PAP – results not definitive.
Plasmapheresis. Has been tested in a few patients with autoimmune PAP – results not promising; approach seems impractical.
Pulmonary macrophage transplantation. In development for Hereditary PAP – results very promising in an animal model.
Gene therapy. Has been effective in animal models of Congenital PAP/Hereditary PAP.

Who Should Be Tested For PAP-Causing Diseases & Testing Options?

All patients with PAP should be tested to identify the causative disease. This is important because each one is caused by a different mechanism and has a different presentation, natural history, most appropriate therapy, treatment response, and prognosis.

Clinical Diagnosis of PAP

Currently, because PAP is so rare, it is often initially misdiagnosed as a more common disease – such as asthma or pneumonia. Only after the failure of several courses of ‘appropriate’ therapy for such diseases prompts further referral and/or reconsideration is PAP usually diagnosed correctly.

The presence of PAP is suggested by a characteristic pattern of symptoms and signs (breathlessness, low blood oxygen level, crazy paving on the chest CT scan) and confirmed by examining a lung biopsy or lung lavage fluid. However, these tests can not identify the disease causing PAP in any patient. No clinical tests are currently available that doctors can use to diagnose most patients with PAP.

‘Clinical Research Diagnosis’ of PAP

Research advances have vastly improved our understanding of how diseases cause PAP. They also led to tests for the ‘clinical research diagnosis’ of PAP that are highly accurate. One such test is the GM-CSF autoantibody ELISA . This blood test is 100% sensitive and 100% specific for a diagnosis of autoimmune PAP. This and other blood tests can identify the disease in more than 90% of PAP patients.

Before these tests can be available to doctors for routine clinical use, they must be validated in clinical research studies. Such studies are an important goal of the National PAP Registry.