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Pulmonary alveolar proteinosis (PAP) is a syndrome characterized
by the accumulation of surfactant lipids and proteins within the
pulmonary alveoli, resulting in impaired gas exchange and respiratory
insufficiency.1 Our understanding of PAP has advanced
significantly over the past several decades due to a series of contributions
from basic, clinical, and translational research.2,3 These
studies have revealed a critical role for pulmonary granulocyte/macrophage-colony
stimulating factor (GM-CSF) in the terminal differentiation of alveolar
macrophages and in alveolar macrophage-mediated surfactant catabolism,
pulmonary surfactant homeostasis, and lung host defense.4-6 PAP
comprises part of a larger group of disorders associated with disruption
of surfactant homeostasis and includes disorders of surfactant production
(hereafter referred to as pulmonary surfactant metabolic
dysfunction disorders) and disorders of surfactant clearance
(hereafter referred to as PAP; Table
518-1). The distinct epidemiological, pathogenic, clinical,
and prognostic features of these two disease categories indicate
they are usually considered separately rather than as a continuum
of a single disease process. PAP can be further divided into primary
and secondary PAP, which, respectively, are associated with either
loss of GM-CSF signaling or the presence of an underlying disorder
that reduces alveolar macrophage numbers or functions.
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Epidemiological studies of disorders of surfactant homeostasis
are hampered by their rarity and values for incidence, and prevalences
provided here are considered estimates. Autoimmune pulmonary alveolar proteinosis (PAP)
is the most common clinical form, accounting for 90% of
all cases, and has an incidence and prevalence of 0.49 and 6.2 per
million, respectively, in the general population.2,15 It is
twice as common in males as females, possibly due to an association
with smoking, typically presents in the third or fourth decade,
and it is rarely observed in children under 10 years old.15,23 Secondary
PAP is the next most common, accounting for 9% to 10% of
cases, with an incidence and prevalence of 0.05 and 0.5 per million,
respectively. Secondary PAP is linked to the occurrence of the underlying
clinical conditions that cause it (Table 518-1). Only
isolated cases ...