Pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a lung disease characterised by abnormal intra-alveolar accumulation of surfactant-like lipoproteinaceous material ^4,6-7.

The disease can be divided into 3 broad categories:

• idiopathic: 90% of cases
  • also termed adult or acquired
• secondary: 5-10% presents in individuals with other precipitating illness e.g.
  • haematological malignancy
  • inhalational lung disease e.g.
    • silicon (known as silicoproteinosis)
    • titanium oxide etc...
  • immunodeficiency/immunosuppression with coexistent infection e.g.
    • nocardiosis
    • aspergillosis
• congenital: 2%
  • presents in neonatal period
  • may be distinct entity also know as chronic pneumonitis of infancy
  • inherent abnormality in surfactant: frameshift mutation on chromosome 2 results in SP-B deficiency

Epidemiology

Pulmonary alveolar proteinosis is rare, and usually presents in young and middle aged adults (20-50 years of age) ^6-7. Smoking is strongly associated with the condition, and in smokers there is a recognised male predilection (M:F of  ~ 2~2:1) ⁶, which is absent in non smoking patients ⁴.

When the disease presents before the age of 1 year, there is an association with thymic alymphoplasia ⁶.

Clinical presentation

Clinical presentation is usually with non specific respiratory symptoms such as dyspnoea or minimally productive cough. ~ 1~1/3^rd of patients may be asymptomatic. In children, the presentation is often less clearly respiratory in nature, with diarrhoea, vomiting, failure to thrive and even cyanosis being more common ⁶. Presentation may also be due to superimposed opportunistic infections (see below).

Signs include crackles on auscultation, clubbing or cyanosis.

Although imaging, bronchial lavage and sputum examination can strongly suggest the diagnosis, lung biopsy is sometimes required ^4,6.

Elevated levels of lactate dehydrogenase and GM-CSF antibodies (in idiopathic forms) are also encountered ⁴.

Pathology

There is deposition of PAS +ve lipoproteinacous material in alveoli as a result of impaired turnover of surfactant. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been implicated in the pathogenesis ⁴. 

A number of opportunistic pathogens may cause a superimposed pneumonia in patients with PAP. Offending agents include ⁴: 

• Aspergillus spp
• Candida spp
• Cryptococcus neoformans
• Cytomegalovirus (CMV)
• Histoplasma capsulatum
• Mycobacterium (tuberculous and nontuberculous)
• Nocardia spp
• Pneumocystis spp
• Streptococcus pneumoniae

Definitive diagnosis is by bronchoalveolar lavage, transbronchial or open lung biopsy.

Radiographic features

As a general rule, radiographic features are often much more severe than the clinical presentation would suggest ⁶.

Plain film

Initial plain chest radiographs can be inconclusive ². Later findings can be variable including: ^4,6. :

• bat wing pulmonary opacities:
  • bilateral central symmetrical lung opacities with relative apical and costophrenic angle sparing
  • reminiscent of pulmonary oedema
  • most common appearance in adults
• diffuse small pulmonary opacities
  • reminiscent of miliary pattern
  • more common in children
• extensive diffuse consolidation
• reticulonodular opacities

Pleural effusions, cardiomegaly and lymphadenopathy usually not features of uncomplicated PAP.

HRCT

The appearance of pulmonary alveolar proteinosis on HRCT is characterised by two main features: 

1. smooth thickening of interlobular and intra-lobular septal lines, and
2. ground glass opacities

The combination of these two features results in what is termed crazy paving pattern, which although a highly characteristic feature is unfortunately not pathognomonic. Additionally pulmonary consolidation or later in the disease pulmonary fibrosis may be evident.

Lung changes are of either patchy or geographic distribution and may have a slight lower lobe predilection ².

Treatment and prognosis

Bronchoalveolar (whole lung) lavage is used therapeutically to remove alveolar material, although its role in children is less certain ⁶.

Complications include

• superimposed infection -: especially with Nocardia asteriodes sp. ¹
• pulmonary fibrosis ( occurs(occurs in ≈ 30≈30%)

Prognosis is variable ranging from improvement (with treatment) to a chronic and terminal course. A 30% 2 year mortality has been reported in adults prior to routine use of bronchoalveolar lavage ⁶. The 5 year mortality has now been reduced to approximately 5% ⁴. In children that figure is much higher due to the reduced efficacy of bronchoalveolar lavage ⁶.

Although double lung transplants have been performed PAP may still recur ⁴.

Differential diagnosis

Imaging differential considerations for specific patterns include:

• crazy paving pattern
• ground glass opacities
• miliary opacities
• bat wing pulmonary opacities
  • pulmonary oedema: pleural effusions and cardiomegaly usually absent in PAP