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Pulmonary Alveolar Proteinosis

Information for Patients

When you are lying on the bed, you are tilted up and down, while a physiotherapist beats your back black and blue. After that, you are sore both on the inside and on the outside, but you welcome the beating as it loosens the surfactant, which helps you breathe more easily.

A Danish PAP patient about lung massage during a whole lung lavage (WLL) procedure. Read more about WLL on page 12

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Introduction Pulmonary Alveolar Proteinosis (PAP) is a rare lung disease, which affects approximately 7 persons in a million people. So despite the fact that you have a very rare disease, you are not the only one. Being diagnosed with a rare, chronic disease may turn your life upside down and significantly change your everyday life. According to experts the best way to deal with the change is to face your disease head on. The more you know about your condition and how to handle it, the more empowered you may feel. This handbook contains information about PAP and deals with subjects such as symptoms, progression and treatment.


PAP in Short PAP is characterised by the build-up of grainy

to clean the air sacs. Consequently, the old

material in the air sacs (alveoli) in your lungs.

surfactant material builds up gradually in your

The grainy material consists of proteins and

lungs and eventually fills the alveoli causing you

lipids from lung surfactant - an important

to feel breathless.

substance that coats the inside of the air sacs to prevent your lungs from collapsing. The air sacs

Scientific research shows that the macrophages

need to be inflated for your lungs to absorb the

need to be stimulated by a protein called

oxygen that you breathe and transfer it to the

Granulocyte Macrophage Colony-Stimulating

blood circulation.

Factor (GM-CSF) in order to function. In PAP lungs, however, the GM-CSF protein is

Your body continuously produces new active

either inactivated or defective, rendering the

surfactant. In healthy lungs the old, inactivated

macrophages or dustmen unable to perform

surfactant is digested by immune cells called

their cleaning tasks.

alveolar macrophages. They are the dustmen or garbage collectors of the body and they have a very important task of keeping the alveoli clean. In PAP lungs, however, the macrophages fail 05

PAP Symptoms When the air sacs in your lungs fill up with

The accumulated surfactant waste material in

surfactant waste it becomes increasingly difficult

your lungs may lead to symptoms such as :

for the blood vessels in the lungs to take up oxygen from the air that you breathe.

- Breathlessness on exertion/activity but

sometimes even at rest

Consequently, you may experience shortness of

- Decreased or decreasing ability to exercise

breath and reduced physical capacity due to the

- Cough, which may be either dry or productive

lack of oxygen, as well as coughing.

with expectoration of whitish mucus

- Chest pain in various types and degrees However, the symptoms vary from person

to person. Some are very affected by the

- Fever or sweats

symptoms in their everyday lives. Others

- Generalised aches and pains

hardly notice any symptoms. But common to

- Fatigue, tiredness, depression or anxiety

all PAP patients is that they are at higher risk of

- In severe cases respiratory failure can occur

acquiring infections because the GM-CSF protein in their immune defense is inactivated or defective. 06

of severity


Diagnosis Your doctor may suspect pulmonary alveolar

densities). The pattern that the images show

proteinosis (PAP) based upon your history

is often referred to as “crazy paving� and is

of symptoms such as breathlessness with

characteristic of PAP, but it is not sufficient to

very slow onset and a physical examination

establish a diagnosis.

revealing a crackling sound when listening with a stethoscope and when other, more common,

Blood test

causes of lung disease have been ruled out.

CT scan

If the doctor suspects that the symptoms may be caused by PAP a specific and very sensitive blood test can be performed. The blood test

Often the physical examination is supported by

can identify an increased presence or absence

a chest x-ray or CT scan. The chest x-ray in PAP

of GM-CSF autoantibodies, which is an indicator

typically reveals the presence of whitish, fluffy

of autoimmune PAP. Similarly, a series of blood

shadows scattered throughout both lungs. The

tests are being developed for the detection of

CT scan images typically reveal extensive white

hereditary PAP.

patches within the lungs (ground glass opacity) with superimposed angular lines (reticular 08



Some doctors use a specialized procedure called

If the examinations mentioned above have

bronchoscopy to conduct a bronchoalveolar

not given any conclusive results about your

lavage (BAL). The BAL fluid is examined to see if

diagnosis, the doctor may choose to perform a

PAP is present.

biopsy of the tissue in your lungs. The biopsy is a surgical procedure called open lung biopsy.

When you undergo a bronchoscopy the doctor passes a bronchoscope into your lungs. A

When an open lung biopsy is performed a

bronchoscope is a tube used to see the inside

general anaesthesia is used, which means you

of the airways and lungs. The doctor sends a

are asleep and pain-free during the procedure.

saline solution through the tube into the lung

A tube is placed through your mouth down

and withdraws it again. This allows the doctor to

your throat to help you breathe. While you are

collect samples of lung cells, fluids, and other

sedated the doctor removes a small piece of

materials inside the air sacs. This part of the

tissue from your lung, which then is examined.

procedure is called a lavage.


Progression PAP usually develops slowly and remains unnoticed until you have accumulated enough surfactant for it to cause symptoms. Over time the disease may progress in several ways: - The disease spontaneously improves and clears - The disease progresses over time - The disease remains stable - The disease is never identified because the patient has no symptoms However, according to doctors most patients experience persistent symptoms that require medical treatment.


Healthy alveoli

PAP affected alveoli


Treatment If treatment is required, the main treatment for

may take several hours and may be interrupted

PAP is washing of the lungs also called whole lung

by lung massage in order for the surfactant to

lavage (WLL). In a WLL procedure sterile saline

come loose.

(salt water) is used to wash the abnormal build up of lung surfactant from the lungs. WLL is carried

Elisabeth, a Danish PAP patient who has had several

out under general anaesthesia where doctors wash

whole lung lavages for the treatment of PAP,

one lung at a time. The other lung is protected

describes the lung massage procedure like this:

from the saline and ventilated with oxygen. When you are lying on the bed,


During the procedure, the doctor (anaesthetist)

you are tilted up and down,

inserts a special double-barrelled breathing tube

while a physiotherapist beats

(called a double-lumen-endobronchial tube)

your back black and blue. After

through the mouth and into the windpipe so that

that, you are sore both on the

the left and right lungs can be isolated from each

inside and on the outside, but

other. The lung is washed until all the ‘milkyness’

you welcome the beating as it

of the lung surfactant is washed out and the

loosens the surfactant, which

fluid is crystal clear. In some cases this

helps you breathe more easily.

After the lung massage, the procedure is repeated.


Any remaining saline is drained out of the lung and both lungs are ventilated with oxygen.

Plasmapheresis is a process that filters the blood and removes harmful antibodies by removing the

Though whole lung lavage is standard treatment

plasma portion of the blood where antibodies

for PAP, some patients are offered other types of

are located. In PAP patients, GM-CSF antibodies

treatment. This is typically because WLL does not

are removed from the blood preventing it from

have the intended effect or because the patients

inactivating the GM-CSF proteins.

are not suited for the treatment.


Investigational therapy As a cure for pulmonary alveolar proteinosis

body's immune system. The immune system is composed of immune cells and the proteins that they produce. These cells and proteins serve to protect the body against harmful bacteria, viruses, fungi, and other foreign invaders.

(PAP) has not been found yet and patients respond differently or sometimes not at all to

Immune modulating medicine is treatment that

the existing treatments, the search for new

uses certain parts of your immune system

effective therapies is a continuous process.

to fight diseases. Clinical trials are ongoing to find out if such medicine can be used to treat

Currently, researchers are conducting clinical

pulmonary alveolar proteinosis (PAP). This can

trials looking into the effect and safety of

be done in a different ways. In the treatment

immune-modulating treatment or immune-

of PAP, immune modulating therapy tested in

suppressive treatment for autoimmune PAP.

clinical trials consists of an immune system

Immune modulating medicine

component called Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), which is given to relieve the symptoms of

Immune modulating medicine also called immunotherapy is medication that affects the 14

the disease.

Experimental treatment with GM-CSF The most common form of PAP, autoimmune PAP, is related to a defective immune control with high levels of antibodies that inactivate GM-CSF. GM-CSF serves to mature and stimulate the cells that defend your lungs against invading germs and regulate the breakdown of inactive surfactant. The discovery of GM-CSF antibodies’ role in PAP has led to the study of GM-CSF as a potential treatment of autoimmune PAP. Treatment with GM-CSF is either given subcutaneously (through a needle under your skin) or as inhalation. A number of clinical studies have been published indicating the efficacy and safety of inhaled GM-CSF in PAP patients. Scientific research also indicate that GM-CSF administration may facilitate restoration of the normal function of immune cells in the lungs (alveolar macrophages).


Experimental treatment with immuno-suppression Another treatment approach that is studied for the treatment of autoimmune PAP is immuno-suppression. Immuno-suppressive therapies reduce the immune response, for example by selectively attacking immune cells which produce excess quantities of antibodies. As such, it is used to decrease the number of B-cells that produce antibodies, such as autoantibodies to GM-CSF antibodies. This may prevent the development of antibodies that inactivate the GM-CSF proteins. The same type of therapy is used for treatment of other diseases related to development of antibodies to your own tissue, such as rheumatoid arthritis and systemic lupus erythematosus. However, at the moment further studies are needed in order to determine the efficacy and safety in PAP patients.


Prevalence PAP is a rare disease. The yearly prevalence

silica, titanium oxide, aluminum, and

(number of patients that are affected by

indiumtin oxide or insecticides, you may

the disease) in USA is 6.9 persons per

also be at increased risk of developing PAP.

million. In Japan, the yearly prevalence is similar (6.2/ million).

Patient characteristics

In Europe, however, the prevalence in

Though PAP is a rare disease the typical

the general population has not been

PAP patient can be characterised by being:

investigated in large studies. But it is assumed to be the same as in USA.

- Aged 25-50 at time of diagnosis - Male (men are 4 times more likely than

If you have other diseases such as HIV or

women to be diagnosed with PAP)

certain types of bone marrow cancer it

- Smoker (the disease seems to be more

increases your risk of developing PAP.

frequent in smokers)

Further to this, if you work in environments where you inhale mineral dust such as 17

Causes When you look for a cause of your disease, it

all is the build-up of waste material from lung

is important to bear in mind that in 90 % of all

surfactant in your lungs. This causes symptoms

cases of PAP there is no known cause.

like shortness of breath and cough.

3 types of PAP

Autoimmune PAP – no known cause

When you are diagnosed with PAP, your doctor will

The most common form of PAP is called acquired or

probably be able to tell you which kind of PAP you

autoimmune PAP. Approx. 90 % of all people with

have. It will be one of the three different forms:

PAP have this type of the disease .

- Autoimmune PAP

Patients suffering from this form have antibodies to

- Secondary PAP

a GM-CSF protein in the blood and the lungs. These

- Congenital/familial PAP

antibodies inactivate the protein so that it cannot function properly. It is not known why some people


The three forms are distinguished by the cause of

develop antibodies to their own GM-CSF. This is why

the disease and the different mechanisms in the

doctors sometimes refer to it as idiopathic PAP as

body that cause symptoms. Common to them

idiopathic means ‘with no known cause’.

Secondary PAP – underlying diseases Secondary PAP is the second most common form of PAP and accounts for approx. 10 % of all PAP patients . Unlike autoimmune PAP it is possible to identify a specific cause of the disease when you have secondary PAP. The cause of secondary PAP may be: - Massive inhalation of toxic substances such as mineral and metal dust - HIV - Some types of cancers - Some types of lung infections

Congenital PAP Congenital PAP is a very rare form of PAP. It is usually diagnosed among infants and young children as it is linked to gene defects. The defects may occur in genes for surfactant proteins or for the receptor transferring GM-CSF signals to the cells. 19

Complications The most common form of PAP, autoimmune

Wash your hands

PAP, is related to a defective immune control


with high levels of antibodies that inactivate the

Regular hand-washing is one of the most

GM-CSF protein. Your body’s defense against

important things you can do to reduce your risk

infections is therefore weakened. This is why

of infection. Wash your hands thoroughly and

you are at higher risk of lung infections and

often, especially when you are around a lot of

other infections, when diagnosed with

people, for example in a hospital or doctor's

autoimmune PAP.

office, or at school or work.

There is a simple and effective way of reducing

Still, always contact your physician if you

the risk of developing infections without you

experience a severe infection or have other

having to live a bubble.


Learn more about PAP If you are looking for more information about PAP, treatment of PAP and/or life with PAP you may find the following websites useful: - The PAP Foundation www.papfoundation.org - PAP Info www.PAP.info - National Organization for Rare Disorders (NORD)


You can also contact your local lung disease patient organisation.


This folder has been produced by Serendex in collaboration with medical specialists who have contributed with their knowledge about a number of aspects about PAP. Serendex Pharmaceuticals Slotsmarken 17 2970 Hørsholm Denmark www.serendex.com Info@serendex.com Tel: +45 7930 1414

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Information for Patients  

Information folder for patients about pulmonary alveolar proteinosis (PAP)

Information for Patients  

Information folder for patients about pulmonary alveolar proteinosis (PAP)

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