What is pulmonary alveolar proteinosis?
Pulmonary alveolar proteinosis, or PAP, is an ultra-rare lung disease in which surfactant (the soapy mixture of fats and proteins that normally keeps the air sacs open) accumulates inside the alveoli. The air sacs gradually fill with this milky material, so less oxygen can pass into the blood.
Normally, cells called alveolar macrophages clear used surfactant. In PAP this clearance fails, most often because of a problem with a signalling molecule called GM-CSF that the macrophages need to work properly.
PAP is divided into three main groups:
- Autoimmune PAP: about nine in ten adult cases, caused by antibodies that block GM-CSF.
- Secondary PAP: linked to blood disorders such as myelodysplasia and leukaemia, heavy inhalation of dusts such as silica, certain infections, or immunosuppression.
- Congenital and hereditary PAP: caused by gene changes affecting surfactant proteins or the GM-CSF receptor, usually in infants and children. See surfactant protein deficiency.
Symptoms of PAP
- Gradually increasing breathlessness: the main symptom, developing over months.
- Cough: usually dry, occasionally with whitish or chunky sputum.
- Fatigue and weight loss.
- Fever: this suggests infection, a known complication.
- Finger clubbing and cyanosis in more advanced disease.
A characteristic feature is that the CT scan often looks much worse than the patient feels. Some people have few symptoms despite extensive changes. Patients with PAP are more prone to unusual infections, including Nocardia, mycobacteria and fungi, because their macrophages do not work normally.
Causes and risk factors
Autoimmune PAP is most common in adults aged 30 to 60 and is more frequent in men. Smoking is a well-recognised risk factor. Secondary PAP should be considered in anyone with a blood disorder, on immunosuppressive treatment, or with heavy occupational exposure to silica, aluminium, titanium or other fine dusts (relevant in quarrying, sandblasting and stone-cutting work). Congenital forms are inherited and present in newborns or young children.
In India, PAP is sometimes initially treated as tuberculosis or pneumonia because of persistent shadows on the chest X-ray, and patients may receive several courses of treatment before the correct diagnosis is made.
How PAP is diagnosed
| Test | What it shows |
|---|---|
| High-resolution CT | A typical crazy-paving pattern: hazy shadowing with thickened lines between lung lobules, sharply bordered by normal lung |
| Bronchoscopy with bronchoalveolar lavage | Milky, opaque fluid containing material that stains positively with PAS stain |
| Serum anti-GM-CSF antibody | A high level confirms autoimmune PAP |
| Lung function tests and oxygen levels | Reduced gas transfer and low oxygen levels, used to judge severity |
| Blood tests | Blood count and markers such as LDH and KL-6, and screening for blood disorders in secondary PAP |
| Lung biopsy | Rarely needed, if lavage and antibody tests are not conclusive |
A typical CT combined with characteristic bronchoscopic lavage fluid and a positive antibody test is usually enough to establish autoimmune PAP without a surgical biopsy. Children with suspected congenital PAP are investigated with genetic testing and are managed jointly with paediatric pulmonology.
Treatment
Observation
Patients with mild symptoms and normal oxygen levels may be monitored, as a proportion improve without treatment. Stopping smoking is essential.
Whole-lung lavage
Whole-lung lavage remains the standard treatment for patients with significant breathlessness or low oxygen. Under general anaesthesia, with a special double-lumen breathing tube, one lung is repeatedly filled with warm saline and drained to wash out the accumulated surfactant while the other lung keeps the patient oxygenated. The second lung is usually washed on a separate day. Many patients improve markedly and some remain well for years, while others need repeat lavage.
Inhaled GM-CSF
For autoimmune PAP, inhaled GM-CSF (for example molgramostim or sargramostim) replaces the blocked signal and improves gas exchange in many patients. It may be used alone or after lavage, and is now an established option in specialist care.
Other treatments
- Rituximab or plasmapheresis to reduce GM-CSF antibodies, in selected patients who do not respond.
- For secondary PAP, treating or removing the underlying cause, working with haematology where needed.
- For congenital PAP, supportive care, and in some cases lung transplantation or stem cell transplantation, coordinated with paediatric and transplant teams.
- Prompt treatment of infections, and vaccination against influenza and pneumococcus.
Outlook and follow-up
The outlook for autoimmune PAP is generally good with modern treatment. Many patients return to normal activity after lavage or GM-CSF therapy, and the condition sometimes goes into remission. Follow-up includes regular lung function tests, oxygen saturation checks and CT when needed. Secondary PAP depends largely on the underlying cause.
When to seek urgent care
Seek urgent medical help for breathlessness at rest, rapidly worsening breathlessness, blue lips, confusion, or high fever with cough, which may indicate an infection that needs prompt treatment.
Frequently asked questions
Is PAP a type of cancer or infection?
No. PAP is a build-up of surfactant in the air sacs, most often due to an autoimmune process. It is not a cancer and is not contagious, although it can make lung infections more likely.
Is whole-lung lavage painful or risky?
It is done under general anaesthesia, so you do not feel the procedure. It is a specialised procedure carried out by an experienced team with careful monitoring, and serious complications are uncommon.
How often will I need lavage?
This varies. Some patients need only one or two treatments and remain well for years, while others need repeated lavage. Inhaled GM-CSF can reduce the need for repeat procedures in autoimmune PAP.
Why was I treated for tuberculosis first?
PAP causes persistent shadows on the chest X-ray with breathlessness and cough, which can resemble tuberculosis or pneumonia. A CT scan and bronchoscopy usually clarify the diagnosis.
Can PAP go away on its own?
In some patients with mild autoimmune PAP, the condition improves without treatment. Regular monitoring is still needed.
Should I stop smoking?
Yes. Smoking is a recognised risk factor for autoimmune PAP and may reduce the response to treatment.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.