1. Discussion Alveolar Proteinosis

2. Introduction
Intra-alveolar accumulation of lipid and proteinaceous material.
Secondary to impaired clearance of surfactant by alveolar macrophage.
Increased work of breathing
Diminished surface area for gas diffusion
Ultimately respiratory failure.
Not associated with inflammation and lung architecture is typically preserved.

3. Introduction Frequency: 3.76 cases per million
Race: no race predilection
Sex: male/female: 2.65/1, 72% with smoking
Non-smoker: no male predominance
Age: peak:30~50y/o, median age at diagnosis: 39y/o

4. Etiology Congenital PAP Secondary PAP: unknown etiology
Autosomal ressive pattern
Mutation in the genes for (1) surfactant protein B or C, (2)beta chain of receptor for GM-CSF
Secondary PAP: unknown etiology
In association with lysinuric protein intolerance
Inciting agents: aluminum, titanium, silicates, insecticides
Acquired PAP: unknown etiology
GM-CSF neutralizing autoantibody in serum and BAL fluid

5. Clinical symptoms Neonatal respiratory distress Dyspnea: Cough:
Progressive respiratory failure and marked hypoxemia shortly after birth
Prolonged ventilator dependence: slow resolution, persisting atelectasis, pneumonia
Dyspnea:
Most consistent finding in children and young adults
50~80%
Cough:
Occasionally with thick sputum or solid material
80%

6. Clinical symptoms Failure to thrive:
More common in young children and infants
Decreased level of activity and difficult feeding
Uncommon symptoms: chest pain, fever, pneumothorax, hemoptysis

7. Lab studies Arterial blood gas analysis
Low PaO2
Compensated respiratory alkalosis
Latex agglutination test: 100% sensitivity, 98% specificity
Pulmonary function test
Mild restrictive pattern of lung disease
Slightly diminished functional lung volumes
Decreased DLCO

8. Bronchoalveolar lavage
Milky or opalescent aspirate with large alveolar macrophage and increased lymphocytes
Positive for PAS
Elevated SP-A and SP-D
Low level of SP-B

9. Lung biopsy The criterion standard for diagnosis
Transbronchial biopsy: not enough tissue for diagnosis in children
Pathologic finding:
Granular, proteinaceous, fluid-filled alveolar spaces
Cholesterol crystals are sometimes observed
Alveolar structure is generally preserved
Some thickening of interlobular septae
EM:
lamellar bodies and tubular myelin within the alveolar space
Adds little to the diagnosis

10. Image--CXR
Bilateral symmetric air-space opacity, ground-glass appearance
perihilar or basilar predominance("bat wing" distribution)
Air bronchograms are uncommon.
No mediastinum widening, adenopathy, cardiomegaly, pleural effusions.

11. CXR

12. Image--CT scan
Conventional CT: bilateral areas of consolidation and reticulation
HRCT
Crazy paving: patchy, bilateral, geographic areas of ground-glass opacity associated with interlobular septal thickening
Interlobular septal thickening : more frequent in the lower lung zones

13. CT scan

14. Differential diagnosis
Hemosiderosis
Hypersensitivity pneumonitis
Goodpasture syndrome
Pulmonary alveolar microlithiasis
Sarcoidosis
Lymphoma
Bronchioalveolar cell carcinoma

15. Treatment Mechanical ventilation Gene therapy
necessary in children with congenital PAP
Partial liquid ventilation (PLV) offers the advantage of lung lavage combined with ventilator support.
Gene therapy
Intravenous immunoglobulin (IVIG) and GM-CSF therapy

16. Treatment The mainstay of therapy in PAP is whole-lung lavage
improved survival rates
< 20 y/o: 58% response >40 y/o: 90% response
Remove surfactant buildup or minimize the effect of macrophage dysfunction
Other options: extracorporeal membrane oxygenation and lung transplantation

17. Mortality/Morbidity Neonate with congenital alveolar proteinosis
With conventional therapy:100%
Lung transplantation: 5-year survival rate:88±4%
Pulmonary alveolar proteinosis:
<5 y/o: 14±13%
Children with late-onset disease: bets likelihood for survival

18. Prognosis
Highly variable course with clinical and radiological episodes of exacerbation and remission
50% improvement/recovery
30% death

19. Thanks for your attention!!