Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis.

Maintenance of tissue-specific organ lipid compositions characterizes mammalian lipid homeostasis. The lungs and liver synthesize mixed phosphatidylcholine (PC) molecular species that are subsequently tailored for function. The lungs progressively enrich disaturated PC directed to lamellar body surfactant stores before secretion. The liver accumulates polyunsaturated PC directed to very-low-density lipoprotein assembly and secretion, or to triglyceride stores. In each tissue, selective PC species enrichment mechanisms lie at the heart of effective homeostasis. We tested for potential coordination between these spatially separated but possibly complementary phenomena under a major derangement of lung PC metabolism, pulmonary alveolar proteinosis (PAP), which overwhelms homeostasis and leads to excessive surfactant accumulation. Using static and dynamic lipidomics techniques, we compared (1) tissue PC compositions and contents, and (2) in lungs, the absolute rates of synthesis in both control mice and the granulocyte-macrophage colony-stimulating factor knockout model of PAP. Significant disaturated PC accumulation in bronchoalveolar lavage fluid, alveolar macrophage, and lavaged lung tissue occurred alongside increased PC synthesis, consistent with reported defects in alveolar macrophage surfactant turnover. However, microscopy using oil red O staining, coherent anti-Stokes Raman scattering, second harmonic generation, and transmission electron microscopy also revealed neutral-lipid droplet accumulations in alveolar lipofibroblasts of granular macrophage colony-stimulating factor knockout animals, suggesting that lipid homeostasis deficits extend beyond alveolar macrophages. PAP plasma PC composition was significantly polyunsaturated fatty acid enriched, but the content was unchanged and hepatic polyunsaturated fatty acid-enriched PC content increased by 50% with an accompanying micro/macrovesicular steatosis and a fibrotic damage pattern consistent with nonalcoholic fatty liver disease. These data suggest a hepatopulmonary axis of PC metabolism coordination, with wider implications for understanding and managing lipid pathologies in which compromise of one organ has unexpected consequences for another.

Pulmonary alveolar proteinosis and cement dust: a case report.

Pulmonary alveolar proteinosis developed in a 29-year-old white man within 2 years of working as a cement truck driver. Pulmonary alveolar proteinosis (PAP), an uncommon respiratory disorder characterized by the accumulation of phospholipid material within the alveoli, has been described in association with exposure to silica, aluminum oxide, and a variety of dusts and fumes. Although a link between exposure to Portland cement and PAP has not been previously noted, this type of cement contains nearly 20% silica. Lung biopsy material, originally used to diagnose PAP, was reviewed under electron dispersive spectroscopy. Analysis indicated the presence of silica particles within the alveolar fluid and macrophages. A number of items support a causal relationship between exposure to cement dust and PAP: (1) the temporal sequence between assuming job duties and the development of the illness, (2) improvement following removal from further exposure, (3) dusty, unprotected working conditions, (4) the presence of silica within the cement, and (5) the alveolar fluid from periodic acid-Schiff-positive lung tissue.

Pulmonary alveolar proteinosis and aluminum dust exposure.

A 44-yr-old male presented with shortness of breath, diffuse X-ray infiltrates, and physiologic evidence of a restrictive lung disease. Biopsy revealed pulmonary alveolar proteinosis. The patient had worked for the previous 6 yr as an aluminum rail grinder in a very dusty environment. Analysis of his lung tissue revealed greater than 300 X 10(6) particles of aluminum/g dry lung; all of the particles appeared as spheres of less than 1 mu diameter. We believe that this case represents an example of pulmonary alveolar proteinosis induced by inhalation of aluminum particles; this finding confirms animal studies which suggest that proteinosis can be produced by very large doses of many types of finely divided mineral dust.