Figures
- Figure 1
PAP pathogenesis. In normal surfactant homeostasis (bottom right), surfactant is synthesised by type II alveolar epithelial cells and secreted into the alveolar space to generate a thin layer. GM-CSF is a cytokine produced by type II alveolar epithelial cells that binds specific receptors on macrophages; GM-CSF induces the terminal differentiation of alveolar macrophages, allowing an effective surfactant catabolism. In primary PAP (bottom left), altered macrophage activation, due to a dysfunction in GM-CSF signalling, leads to impaired surfactant clearance and to the consequent accumulation of surfactant. In autoimmune PAP, GM-CSF signalling is inhibited by the presence of neutralising GM-CSF autoantibodies; the hereditary form is the result of mutations involving the GM-CSF receptor. In secondary PAP (top left), various underlying conditions can affect the number and/or the function of the alveolar macrophages, causing reduced surfactant clearance and surfactant accumulation within the alveoli. In congenital PAP (top right), mutations in SFTPB, SFTPC, ABCA3 and TTF1 interfere with the production of surfactant which, in turn, is ineffective and prone to accumulation.
- Figure 2
Chest HRCT findings in PAP. a) Interlobular septal thickening within interspersed ground glass (“crazy paving” pattern) is spread symmetrically to all five lobes with a perihilar predominance. b) After whole-lung lavage treatment, the crazy paving pattern is still appreciable but with reduced distribution and lower alveolar infiltration.
- Figure 3
Diagnostic algorithm of PAP syndrome. PAP can be suspected based on a congruent clinical picture, compatible chest HRCT findings and an evocative BAL fluid. BAL fluid cytological analysis can confirm the diagnosis of PAP syndrome; subsequently, the diagnostic effort is directed to the identification of the specific PAP-causing disease. In the absence of a clear PAP-causing disease, GM-CSF autoantibody measurement should be performed to identify autoimmune PAP, the most frequent aetiology of PAP. Low levels of GM-CSF autoantibodies exclude the diagnosis of autoimmune PAP and dictate further investigations: accurate research of possible secondary PAP-causing disease, serum GM-CSF measurement and GM-CSF signalling test. High levels of serum GM-CSF indicate GM-CSF receptor dysfunction, highlighting hereditary PAP, which can be confirmed by the GM-CSF signalling test and specific gene analysis. Normal levels of serum GM-CSF and a GM-CSF signalling test within normality suggest the presence of congenital PAP that should be assessed with specific genetic tests [4]. LDH: lactate dehydrogenase.
- Figure 4
WLL schematic procedure. WLL is an invasive procedure almost universally performed under general anaesthesia, in an intensive care unit. In this example, the patient lies in the full lateral position; selective ventilation is assured by using a double-lumen endobronchial intubation. The lung above undergoes the lavage, while the other is selectively ventilated; an aliquot of warm saline is infused by gravity into the nonventilated lung and the collection tube is clamped. Subsequently, the aliquot is drained from the lavaged lung and received by gravity by the fluid collector. These passages are repeated until the collected fluid turns clears or until achievement of the programmed total infusion volume for each lung. Chest percussion can be associated during the procedure in order to emulsify the surfactant sediment.
Tables
- Table 1
Classification of PAP
Primary PAP: GM-CSF signalling disruption Autoimmune PAP (GM-CSF autoantibodies)
Hereditary PAP (mutations in genes encoding GM-CSF receptor)
Secondary PAP: reduction in function and/or number of alveolar macrophages Haematological disorders
Malignancies
Immune deficiency syndromes
Chronic inflammatory syndromes
Chronic infections
Toxic inhalation syndromes
Other
Congenital PAP: impaired surfactant production Mutations in surfactant proteins (SFTPA, SFTPB, SFTPC)
Mutations in lipid transporter (ABCA3)
Mutations affecting lung development (TTF1)
GM-CSF: granulocyte–macrophage colony-stimulating factor.
- Table 2
PAP clinical manifestations
No symptoms
31.4%
Exertional dyspnoea
39.0%
Cough
9.9%
Dyspnoea and cough
10.9%
Dyspnoea and sputum
1.3%
Dyspnoea, cough and sputum
2.2%
Other
4.0%
Jump To
- Article
- Abstract
- Abstract
- Pulmonary alveolar proteinosis: a respiratory syndrome rather than a single disease
- PAP: rare and rarest forms
- The importance of pulmonary surfactant in all PAP forms: composition, function and homeostasis
- When to suspect PAP: clinical, radiological and functional aspects
- From clinical suspicion to PAP diagnosis, step by step
- PAP clinical course
- Different PAP forms, different therapies
- Conclusions
- Footnotes
- References
- Figures & Data
- Info & Metrics