Pulmonary alveolar proteinosis is a pathologic entity characterized by intraalveolar surfactant accumulation. There are 3 clinically distinct forms: hereditary (usually congenital), secondary, and acquired. The acquired form of pulmonary alveolar proteinosis is the most common form, accounting for approximately 90% of cases. The mean age at diagnosis is 39 years and it is associated with smoking in 72% of cases. The estimated incidence and prevalence are 0.36 and 3.70 cases per million, respectively (Trapnell et al., 2003; Seymour and Presneill, 2002). Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages. Such conditions include some hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections. Congenital pulmonary alveolar proteinosis is a rare, severe, often fatal disorder of newborns associated with pulmonary surfactant metabolism dysfunction caused by mutations in genes involved in surfactant metabolism (see, e.g., SMDP1, 265120) (Trapnell et al., 2003). See 300770 for information on congenital PAP due to CSF2RA (306250) deficiency.

Telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-8 (PFBMFT8) is an autosomal dominant disorder characterized by the onset of progressive pulmonary fibrosis in adulthood. Some affected individuals have signs of bone marrow failure, such as thrombocytopenia, or liver dysfunction, including hepatopulmonary syndrome. Other features of dyskeratosis congenita, including premature graying of the hair, may be observed. Telomeres are shortened compared to controls (Kelich et al., 2022). For a discussion of genetic heterogeneity of telomere-related pulmonary fibrosis and/or bone marrow failure, see PFBMFT1 (614742).