QUESTIONS ABOUT PAP
What is PAP?
PAP is a syndrome (clinical condition) in which surfactant, a milky substance
normally present in the lungs, accumulates to abnormally high levels and causes
a feeling of breathlessness. In general, the term "syndrome" is used when
a group of symptoms and signs occur together and characterize the particular
clinical condition. The term disease is used when the clinical condition is
actually caused by a specific abnormality. In other words, PAP is not a
single disease but, rather, a group of diseases that cause a similar set of
symptoms and physical findings, more or less.
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What are the different types of PAP?
PAP is known to occur in three different clinical forms; primary (also called
idiopathic or occasionally acquired), secondary and congenital forms.
Primary PAP is associated with high levels of antibodies that recognize and
neutralize an essential blood protein called GM-CSF (granulocyte-macrophage
colony-stimulating factor). Secondary PAP occurs as a consequence of
another clinical condition that reduces either the numbers or function of
alveolar macrophages. Congenital PAP is a less-well characterized
collection of specific lung diseases that are due to genetic defects in the
genes responsible for production of normal surfactant.
What causes PAP to occur in the first place?
PAP is a condition in which surfactant, a normal milky substance lining the
lungs, accumulates to abnormally high levels and results in a feeling of
breathlessness. There are several different clinical forms or types of
PAP; primary (also called idiopathic or occasionally acquired), secondary and
congenital forms. Primary PAP is associated with high levels of antibodies
that recognize and neutralize an essential blood protein called GM-CSF
(granulocyte-macrophage colony-stimulating factor). Secondary PAP
occurs as a consequence of another clinical condition that reduces either the
numbers or function of alveolar macrophages. Congenital PAP is a less-well
characterized collection of specific lung diseases that are due to genetic
defects in the genes responsible for production of normal surfactant.
What are the Symptoms of PAP?
Primary PAP usually starts without notice and then gradually gets worse until a
feeling of breathlessness (dyspnea) becomes apparent and progresses. Some
patients also have cough and / or may produce small amounts of whitish phlegm
(sputum). Fever can be present if infection is also present. Rarely,
an affected individual may cough up blood (hemoptysis) or have chest pain,
especially if lung infection is also present.
How is PAP diagnosed?
PAP can be suspected on the basis of clinical symptoms (dyspnea) and the results
of a chest x-ray and/or chest CT scan. The chest x-ray in PAP typically
reveals the presence of whitish, fluffy shadows scattered throughout both lungs
(referred by doctors as a diffuse, bilateral alveolar filling or ground glass
pattern). The chest CT scan in PAP typically reveals a pattern commonly
referred to as "crazy paving", which consists of areas of increased whitish
shadows (ground glass opacities) adjacent to areas of normal appearing lung (a
geographic distribution) scattered throughout the lungs that is superimposed on
thick white lines (septal wall thickening).
Notwithstanding clinical suspicion, PAP is still diagnoses by directly observing
the abnormal appearance of a sample of the abnormal lung tissue (lung biopsy).
A lung biopsy can be obtained during bronchoscopy (called a transbronchial
biopsy) or by the surgeon (an open lung biopsy).
A new technique, referred to as the "anti-GM-CSF antibody titer" determination,
is currently being used in clinical research studies to identify individuals
with primary PAP. High levels of anti-GM-CSF antibodies are
present in individuals with primary PAP, but not secondary PAP, congenital PAP,
other lung diseases or normal, healthy individuals. The anti-GM-CSF
antibody titer test is currently in a period of testing to determine how well it
predicts the presence of primary PAP in individuals suspected of having the
disorder. Investigators hope that current studies will establish this test
as a simple and very useful tool that can be used to diagnose primary PAP in the
What is GM-CSF and how is it related to primary PAP?
GM-CSF is a cytokine required to stimulate certain lung cells (alveolar
macrophages) to destroy (catabolize) surfactant. The ability of GM-CSF to
stimulate alveolar macrophages to destroy surfactant results in removal
(clearance) of surfactant from the lungs. In fact, GM-CSF is required to
stimulate the ability of alveolar macrophages to remove excess surfactant.
Antibodies that recognize GM-CSF and are capable of neutralizing its function
(neutralizing anti-GM-CSF autoantibodies) effectively eliminate the function of
GM-CSF bound by the antibody. This, in turn, prevents GM-CSF from
activating surfactant destroying pathways in alveolar macrophages and thus
blocks their ability to remove excess surfactant, which then accumulates
What is the natural history of PAP?
PAP can follow one of three different pathways over time. In the first group,
patients have an improvement in their symptoms either spontaneously or after one
or more whole lung lavages. In the second group, the symptoms continue without
spontaneous improvement or worsening. In the third group, the clinical symptoms
What are the treatment options for PAP?
Whole lung lavage is the most commonly used treatment for primary PAP and is
currently considered to be "standard therapy".
In addition standard therapy, several new "experimental" approaches for the
treatment of PAP are currently under evaluation in clinical research studies.
One form involves GM-CSF administration, either by injection under the skin
(subcutaneous administration) or by breathing in a fine mist of saline that
contains GM-CSF (aerosol administraion). Another involves a procedure known as
plasmapheresis in which antibodies are removed from the blood stream.
Another therapy involved treatment to reduce the number of antibody-secreting
blood cells (B lymphocytes).
What is a lung lavage?
Whole lung lavage is a procedure in which the patient is placed under general
anesthesia, a double-lumen endotracheal tube (a special "Y" shaped plastic
breathing tube) is positioned with one end of the "Y" in each lung and the other
end protruding out from the windpipe (trachea) and mouth. This allows air to be
moved into and out of one lung using a ventilator (mechanical breathing machine)
while saline (salt water solution)is flowed into and drained out of the other
lung to "wash out" the excess surfactant. Approximately 15 to 50 liters of
saline is used to wash each lung. After completing the lavage of the firs lung,
the second lung is washed. In most, but not all centers, there is a period of
one or more days between lung lavages to allow the patient to recover.
How common is PAP?
PAP is a rare disorder. The number of people affected by PAP has been estimated
to be about 3.7 per million individuals.
How will having PAP affect my lifestyle?
PAP affects the lungs by causing surfactant to accumulate to abnormally, thus
reducing the ability of the lung to transfer oxygen from the air into the blood.
This has the effect of making an individual with moderate or severe PAP feel
"breathless" or "short of breath". The reduced uptake of oxygen into the
bloodstream is worse at times of increased exercise. This causes an awareness of
"exercise-induced breathlessness". The net effect of this limitation is
that people with PAP may have more trouble with mild or strenuous activities.
This is what doctors refer to as exercise limitation.
Sometimes, PAP patients need oxygen therapy. This usually involves the
use of a portable oxygen tank and a plastic tube that rests over the ears and
drapes under the nose and across the upper lip projecting oxygen into the nose.
Breathing in a higher concentration of oxygen in each breath helps because the
lung surface is exposed to gas with a higher percentage of and this results in
more oxygen transferred into the bloodstream for each breath taken.
The current standard of care for treating PAP is whole lung lavage.
Published medical literature reports that this procedure is needed every 15
months, on average, by those that require it. The procedure is performed
in the hospital, so patients need to be admitted to the hospital periodically.
Where can I find detailed information (published medical literature) about PAP?
Click here to find published papers about PAP
What research is being performed to better understand PAP occurs and to develop
new treatments for PAP?
Studies to evaluate new therapies for
PAP are being organized by the Rare Lung Diseases Consortium.
for more information.
How can I help in the
development of new therapies for PAP?
You can help by learning about
and participating in the ongoing research studies to develop new diagnostic
methods and therapy for PAP. The Rare Lung Diseases Consortium (RLDC) is a group
of clinical research centers and patient organizations (the Rare Lung Disease
Foundation Consortium) who are collaborating together to speed the pace of PAP
research and development.
for more information about the RLDC.
How can I help the PAP
You can help the PAP Foundation is
several important ways. You can become a volunteer. We need help with
fundraising. You can make a donation yourself. You can help in the development
of educational materials about PAP. You can help raise awareness about PAP.
Please contact us if you have questions or would like to discuss other ways in
which you can help.
Where can I find a Doctor who is familiar with PAP?
Click here to for a list of doctors who are
familiar with PAP.
Is there a support group for people affected by PAP?
Yes. Lou Schimpf has maintained an online support for PAP patients,
friends and family for several years.
Click here to join.
Click here to see the glossary.