Pulmonary Alveolar Proteinosis

McClenahan, James B.

doi:10.1001/archinte.1974.00320140122013

Cited by 29 publications

(6 citation statements)

References 20 publications

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“…3A). 54 The results of ultrastructural, 37,55 biochemical, 56,57 and functional 58 investigations, together with the results of studies in genetically modified mice (discussed below), strongly support the concept that the alveolar material in pulmonary alveolar proteinosis is in fact surfactant, which accumulates due to reduced clearance rather than to overproduction. 49 In their initial description of pulmonary alveolar proteinosis, 1 Rosen et al established that the eosinophilic material within the alveoli was rich in lipids and that it contained proteins and carbohydrates.…”

Section: Pathological Featuresmentioning

confidence: 85%

Pulmonary Alveolar Proteinosis

2003

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Section: Pathological Featuresmentioning

confidence: 85%

Pulmonary Alveolar Proteinosis

2003

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“…Early studies by Ramirez-Rivera and Harlan (3) and McClenahan and Mussenden (4) suggest that surfactant synthesis and secretion in patients with AP is normal and that accumulation arises through an impairment in surfactant removal.…”

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confidence: 99%

Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis

Doyle

Davidson

Barr

et al. 1998

Am J Respir Crit Care Med

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Alveolar proteinosis (AP) is an idiopathic condition characterized by excess alveolar surfactant. Although the surfactant proteins (SP) are known to be aberrant, little is known of their variation between patients or their abundance relative to the lipids. We have examined surfactant composition in lavage fluid from 16 normal subjects and 13 patients with AP, one of whom was lavaged on 11 occasions over approximately 13 mo. In this patient we have examined composition on each occasion and in each sequential lavage aliquot. Composition was constant between right and left lung, but it differed markedly between patients. The cholesterol/disaturated phospholipid ratios (CHOL/DSP) were invariably elevated, on average by approximately 7-fold, whereas the SP-A/DSP and SP-B/DSP ratios were generally elevated, in some cases by as much as approximately 40- and approximately 100-fold, respectively. Although AP lavage generally contained more non-thiol-dependent SP-A aggregates and low Mr isoforms, the two-dimensional immunochemical staining patterns varied between patients and right and left lung. In the patient lavaged on multiple occasions, the SP-A/DSP and SP-B/DSP ratios progressively decreased as the patient's condition resolved. Because the SP-B/SP-A ratio was normal in all cases, we suggest that structural changes to the proteins occurred secondarily and that caution must be used in comparing functional data derived using SP-A obtained from patients with AP.

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“…2,8 Histopathology Analysis of BAL fluid has revealed increased concentrations of lipids and proteins, particularly those associated with surfactant. The classes and distribution of surfactant phospholipids do not substantially differ from normals, 54,55 though there is much variability. Cholesterol concentrations are consistently elevated.…”

Section: Diagnostic Evaluationmentioning

confidence: 82%

“…59 This accumulated PAP material has been shown to have normal surface activity after processing. 54 A small study of cells in the BAL fluid revealed an increase in both the CD4 and CD8 lymphocyte population. 60 The CD4:CD8 ratio tended to be high but was variable.…”

Section: Diagnostic Evaluationmentioning

confidence: 99%

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Pulmonary Alveolar Proteinosis: Recent Advances

Mazzone¹,

Thomassen²,

Kavuru³

2002

Seminars in Respiratory and Critical Care Medicine

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Pulmonary Alveolar Proteinosis (PAP) is characterized by the accumulation of surfactant phospholipids and proteins within the alveoli of lungs. Currently, no specific therapy exists for PAP, and sequential whole lung lavage is standard treatment. Over the past 5 years, important advances have been made in our understanding of alveolar proteinosis, offering new directions for research as well as patient management. First, genetically altered mice that are homozygous for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene developed a lung lesion with histologic resemblance to PAP, along with normal hematopoiesis. The biochemical properties of the material filling the airspaces in these mutant mice are similar to those of patients with PAP. Surfactant is thought to be cleared or catabolized mostly by alveolar macrophages, a process dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found in bronchoalveolar lavage fluid and serum of patients with idiopathic PAP, but not healthy controls. These observations raise the previously unsuspected notion that human alveolar proteinosis may be an autoimmune disease, and suggest that GM-CSF antibody has a potential role as a diagnostic test. The relationship between the antibody and disease pathogenesis remains unknown. Additional data suggest that exogenous therapy with GM-CSF may improve the lung disease in some patients with PAP. Intervention directed at treating a relative GM-CSF deficiency or lowering the antibody (i.e., by plasmapheresis or immunosuppression) may have promise in the therapy of this disease. Alveolar proteinosis may be the first human disease wherein a circulating antibody against a growth factor is linked to disease pathogenesis. Over a relatively short time, studies from ;;knock-out'' mice have been translated to human studies for a new approach to diagnosis and therapy for this disease.

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Pulmonary Alveolar Proteinosis

Cited by 29 publications

References 20 publications

Pulmonary Alveolar Proteinosis

Pulmonary Alveolar Proteinosis

Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis

Pulmonary Alveolar Proteinosis: Recent Advances

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