Pulmonary alveolar proteinosis

Very rare. Intraalveolar accumulation of milky-looking lipoprotein-rich PAS positive fluid (surfactant). The surfactant is the tensioactive liquid layer that lines the pulmonary alveoli to prevent their collapse at the end of exhalation. It is produced in and secreted by the type II pneumocytes, and recycled by the type II pneumocytes or catabolized by the alveolar macrophages. The activity of these macrophages depends on their activation by the GM-CSF. The surfactant is a mixture of phospholipids and hydrophilic (SP-A, SP-D) and hydrophobic (SP-B, SP-C) proteins.


Several clinical presentations:


Etiologies:


Primary forms following a congenital abnormality of the surfactant's metabolism;


-        autosomal recessive transmission of a mutation of the SFTPB gene (2p12) coding for the surfactant protein B:   neonatal hyaline membranes disease

-        autosomal dominant transmission of a mutation of the SFTPC gene (8p21) coding for the surfactant protein C:  neonatal hyaline membranes disease or interstitial alveolar lung disease

-        autosomal recessive transmission of a mutation in the ABCA3 gene (16p13) coding for the ABCA3 ATP-binding cassette: neonatal hyaline membrane disease or interstitial alveolar lung disease with onset in childhood

-        autosomal dominant transmission of a mutation in the NKX2-1 gene (14q13) coding for the TTF-1 protein: variable onset age; associated with hypotonia, hypothyroidism and chorea

-        autosomal coding for transmission of a mutation of the MARS1 gene (12q13.3)(pulmonary alveolar  proteinosis of  La Réunion island)[MIM 615 486] coding for methionyl-tRNA synthetase. Failure to activate the alveolar macrophages by the GM-CSF resulting in an abnormality of the surfactant's catabolism. Associated with liver dysfunction: steatosis, fibrosis, sometimes cirrhosis. Variable age of  onset, associated with liver dysfunction


-        autosomal recessive transmission of a mutation in the CSF2RA gene (Xp13) coding for the receptor α of  the GM-CSF: onset in infancy

-        autosomal recessive transmission of a mutation in the CSF2RB gene (22p13) coding for the receptor β of  theGM-CSF: onset in infancy




Secondary forms


1)        hematological diseases: malignant hemopathies, myelofibrosis, bone marrow aplasia, congenital or acquired cellular immunodeficiency (HIV), alymphocytosis ...

2)        infection: Pneumocystis carinii, Nocardia, cryptococcosis, mycobacteria, CMV

3)        inhalation of toxics: metal particles (Al, Cu, Ni, Ti, In ...), minerals (silica, cement, fiberglass, talc, kaolin...), organic (cellulose), vapours (painting, varnish, fuel, epoxy resin..), PVC, fertilizer ...

4)        alveolar proteinosis associated with hypogammaglobulinemia [MIM 618 042] in the context of a gain of function mutation of the OAS1 (12q24.13) gene (PAPHG syndrome, for Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia). Repeated infections. Need for bone marrow transplantation.


autoimmune form  (90% of causes in adults): presence of anti-GM-CSF antibodies


Treatments:



Primary forms: corticosteroids, and azithromycin or hydroxychloroquine in case of mutation of the SFTPC, ABCA3 or NKX2-1 genes

Secondary forms: depending on the causal pathology (e.g. bone marrow transplant in malignant hemopathies)

Autoimmune form: in addition to repeated bronchoalveolar lavage, administration of GM-CSF subcutaneously or by aerosols; plasmapheresis or rituximab.


Anesthetic implications: 

chronic hypoxemia and risk of cor pulmonale; chest X-Ray + SpO2 at room air; for bronchoalveolar lavage: TIVA and selective pulmonary intubation [double lumen tube, intubation and fiberscopic bronchial washing, intubation and Swan-Ganz catheter inserted in the bronchus of the lung to be washed], or  repeated apnea in a hyperbaric chamber or cardiopulmonary bypass.


References : 


Updated: December 2021