Pulmonary Alveolar Proteinosis

Rare lung disorder of unknown aetiology. Alveolar spaces become filled with an amorphous, largely cell-free, lipoproteinaceous material that is not easily cleared from the lungs. The lungs become stiff with restricted ventilatory function. Secondary infection may occur. Two forms are recognised:¹

• Primary: idiopathic.
• Secondary: due to lung infections, haematological malignancies, inhalation of mineral dusts (e.g. silica, titanium oxide, aluminum) and insecticides.

It is thought that impairment of surfactant clearance by alveolar macrophages, by autoantibody inhibition of the action of granulocyte-macrophage colony-stimulating factor (GM-CSF), may underlie many acquired cases, whereas congenital disease is most commonly attributable to mutations in surfactant protein genes, but may also be caused by GM-CSF receptor defects. Therapy with GM-CSF has shown promise in acquired cases of pulmonary alveolar proteinosis.²

• The estimated prevalence is 1 case per 100,000 population.
• It is more common in males than females.
• Incidence is increased in patients with haematological malignancies and AIDS, suggesting a relationship with immune dysfunction.
• Pulmonary alveolar proteinosis is probably underdiagnosed.

• Inhalation of silica dust (acute silico-proteinosis)
• Exposure to insecticides, aluminum dust, titanium dioxide, and other inorganic dusts
• Haematologic malignancies, mostly myeloid disorders
• Lysinuric protein intolerance (rare)
• HIV infection

• Usually presents at aged 20-50 years with a gradual onset of symptoms.
• As many as 30% of patients are asymptomatic, even with diffuse chest x-ray abnormalities.
• Symptoms Include:
  • Persistent dry cough (or scant sputum production)
  • Progressive dyspnoea
  • Fatigue and malaise
  • Weight loss
  • Intermittent low-grade fever and/or night sweats
  • Pleuritic chest pain
• Signs are usually non-specific and include:
  • Fine end-inspiratory crackles
  • Clubbing
  • Cyanosis

Any cause of increasing dyspnoea but particularly:

• Hypersensitivity pneumonitis
• Pneumocystis jiroveci (carinii) pneumonia
• Pulmonary oedema
• Sarcoidosis
• Lipoid pneumonia
• Acute respiratory distress syndrome

• Serum lactate dehydrogenase (LDH) is usually elevated, but this finding is non-specific.
• Chest x-ray: bilateral peri-hilar infiltrates with consolidation. Changes progress into a diffuse reticulogranular pattern.
• Flexible bronchoscopy with bronchoalveolar lavage: alveolar secretions are PAS-positive but contain no organisms or any excessive cellular response.
• High-resolution CT scan of the chest: patchy ground-glass opacification with interlobular thickening. Appearance similar to that seen in lipoid pneumonia, sarcoidosis and acute respiratory distress syndrome.
• Lung biopsies: transbronchial biopsies are adequate. Alveoli are filled with non-foamy material. Surgical lung biopsy rarely is necessary.

• Depends on the progression of the illness, co-existing infections, and degree of physiological impairment.
• Mechanical removal of the lipoproteinaceous material by whole-lung lavage.³
  • This is performed under general anaesthesia, and the lung is ventilated briefly with 100% oxygen before lavage with isotonic sodium chloride solution.
  • Lung lavage may take several hours.
• Appropriate treatment of any underlying cause.
• Lung transplantation is the treatment of choice in patients with congenital PAP and in adult patients with end-stage interstitial fibrosis and cor pulmonale.
• In the past, patients have also been treated with systemic steroids and aerosol mucolytics, but without much success.

• Lung infections: often Nocardia asteroides, Pneumocystis jiroveci (carinii), or Mycobacterium avium
• Pulmonary fibrosis
• Pulmonary hypertension
• Cor pulmonale

• In a third of patients, no appreciable disability develops and the disease remits spontaneously or fails to progress. The natural history depends on the underlying aetiology.
• Estimates of 5-year mortality rates vary between 10% and 30%.
• Whole-lung lavage often produces a dramatic response. Patients who require repeated lavages usually progress to pulmonary fibrosis and have a poor outcome.
• Lung transplantation for congenital pulmonary alveolar proteinosis often has a good outcome.

• Patients prone to alveolar proteinosis related to inhalation of inorganic dusts or insecticides should avoid further exposure.