OVERVIEW

What is Pulmonary Alveolar Proteinosis?

Pulmonary alveolar proteinosis refers to a clinical syndrome characterized by the abnormal deposition of pulmonary surfactant in the alveoli and terminal respiratory bronchioles, leading to restrictive ventilatory dysfunction and impaired pulmonary diffusion capacity, ultimately progressing to respiratory failure.

The main symptoms of this disease include exertional dyspnea and cough. Whole-lung lavage is the primary treatment method, while other empirical therapies show some clinical efficacy, though their safety and effectiveness require further validation.

The onset of this disease is insidious, and its prognosis varies. Mild cases may improve spontaneously, while severe cases can progressively deteriorate into respiratory failure. Isolation is not required during the illness, but the patient's quality of life is significantly affected.

Is Pulmonary Alveolar Proteinosis Common?

It is uncommon and predominantly affects adult males. Certain types may have a genetic predisposition.

What Are the Types of Pulmonary Alveolar Proteinosis?

• Idiopathic Pulmonary Alveolar Proteinosis: Primarily caused by impaired clearance of pulmonary surfactant due to defects in the granulocyte-macrophage colony-stimulating factor signaling pathway. It mainly includes autoimmune and hereditary (congenital) types.

• Secondary Pulmonary Alveolar Proteinosis: This type is associated with various underlying diseases, where reduced numbers or impaired function of pulmonary macrophages due to the primary condition disrupt surfactant metabolism.

  Common underlying conditions include hematologic disorders (e.g., myelodysplastic syndromes), non-hematologic malignancies (e.g., lung adenocarcinoma, malignant glioma, melanoma), infectious diseases (e.g., cytomegalovirus, Mycobacterium tuberculosis, pneumocystosis), immunodeficiency disorders, and exposure to harmful substances.

SYMPTOMS

What are the common manifestations of pulmonary alveolar proteinosis?

• Common clinical manifestations include exertional dyspnea, cough, fatigue, and weight loss, while fever and sputum production are less frequent.

• Patients secondary to myelodysplastic syndrome most commonly present with fever, exertional dyspnea, and cough.

• Autoimmune pulmonary alveolar proteinosis patients often have a history of smoking, and exposure to dust or exhaust fumes has also been reported.

• Physical examination is usually unremarkable, though some patients may exhibit crackles, clubbing, or cyanosis.

How does pulmonary alveolar proteinosis progress?

The onset of the disease is insidious, with slow progression. Early recognition is challenging because clinical symptoms only appear when a significant number of alveoli are filled with surfactant material.

The progression of autoimmune pulmonary alveolar proteinosis typically follows one of three patterns:

• Spontaneous improvement;
• Persistent, non-resolving condition;
• Progressive respiratory failure.

Secondary pulmonary alveolar proteinosis varies in clinical course depending on the underlying disease and generally has a poorer prognosis.

CAUSES

What causes pulmonary alveolar proteinosis?

Any condition that leads to increased secretion, reduced uptake, or decreased breakdown of pulmonary surfactant can cause abnormal accumulation of surfactant in the alveoli and terminal respiratory bronchioles, resulting in impaired respiratory function.

These causes include defects in the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway (idiopathic pulmonary alveolar proteinosis), high levels of GM-CSF autoantibodies in the lungs (autoimmune pulmonary alveolar proteinosis), genetic mutations (hereditary or congenital pulmonary alveolar proteinosis), and reduced number or dysfunction of alveolar macrophages due to underlying diseases (secondary pulmonary alveolar proteinosis).

Who is most commonly affected by pulmonary alveolar proteinosis?

It is more common in adult males.

Is pulmonary alveolar proteinosis contagious?

No.

Is pulmonary alveolar proteinosis hereditary?

Hereditary (congenital) pulmonary alveolar proteinosis has a genetic predisposition.

DIAGNOSIS

How is pulmonary alveolar proteinosis diagnosed?

To diagnose this condition, doctors need to consider medical history, typical imaging findings, bronchoalveolar lavage cytology, lung biopsy, and biomarker tests. Additionally, secondary pulmonary alveolar proteinosis requires further evaluation of the underlying disease through relevant auxiliary examinations.

What tests are needed for pulmonary alveolar proteinosis?

• Laboratory tests: Routine lab tests are usually normal, though serum LDH may be elevated. Detection of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in serum is crucial for diagnosing autoimmune pulmonary alveolar proteinosis.

• Imaging studies: Chest CT can reveal the extent of lung lesions and help assess disease severity.

• Bronchoscopy and bronchoalveolar lavage: Bronchoscopy typically shows no significant abnormalities, but the lavage fluid may appear milky with thick sediment. Bronchoalveolar lavage is an effective diagnostic and differential diagnostic tool for this condition.

• Histopathology: When the disease is strongly suspected based on bronchoalveolar lavage and serum GM-CSF antibody tests, histopathological examination can confirm the diagnosis.

• Pulmonary function tests: These mainly reveal restrictive ventilatory dysfunction and reduced diffusion capacity.

TREATMENT

Which department should I visit for pulmonary alveolar proteinosis?

Respiratory Medicine.

Can pulmonary alveolar proteinosis heal on its own?

Approximately one-third of patients may experience spontaneous improvement.

How is pulmonary alveolar proteinosis treated?

• Whole lung lavage is the preferred treatment method.

• Secondary pulmonary alveolar proteinosis primarily focuses on treating the underlying disease.

• Other empirical treatment methods have shown some clinical efficacy, but their safety and effectiveness require further confirmation.

Does pulmonary alveolar proteinosis require hospitalization?

Yes.

Can pulmonary alveolar proteinosis be cured completely?

No.

DIET & LIFESTYLE

What should patients with pulmonary alveolar proteinosis pay attention to in their diet?

Maintain a healthy diet and ensure adequate nutrition.

Does pulmonary alveolar proteinosis require follow-up examinations? How are they conducted?

Yes, follow-up tests such as hematological indicators, imaging, and bronchoscopy should be performed based on the condition.

PREVENTION

Can Pulmonary Alveolar Proteinosis Be Prevented? How to Prevent It?

Actively treating underlying diseases and boosting immunity can help prevent the occurrence of this condition.

How Can Patients with Pulmonary Alveolar Proteinosis Avoid Triggering Other Diseases?

Early detection, timely diagnosis, and standardized treatment based on the condition.