Pulmonary Alveolar Proteinosis

Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD more...

Updated: Mar 16, 2011

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Background
Pathophysiology
Epidemiology
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Background

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder of unknown etiology characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff (PAS) method and is derived from surfactant phospholipids and protein components (see the image below). PAP was first described in 1958.^[1]

A periodic acid-Schiff histochemical stain of transbronchial biopsy: Alveolar spaces contain considerable amounts of granular material.

Two forms are recognized, (1) primary (idiopathic) and (2) secondary; due to lung infections, hematologic malignancies and inhalation of mineral dusts such as silica, titanium oxide, aluminum, indium-tin oxide and insecticides. Incidence of PAP is increased in patients with hematologic malignancies and AIDS, suggesting a relationship with immune dysfunction. Associations with Niemann-Pick disease^[2]and myelodysplastic syndrome^[3]have been reported.

A similar disorder affects neonates deficient in surfactant-associated protein B (SP-B).

The discovery that PAP may be related to granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies or GM-CSF deficiency has been noted.

Pathophysiology

The alveoli in pulmonary alveolar proteinosis (PAP) are filled with proteinaceous material, which has been analyzed extensively and determined to be normal surfactant composed of lipids and surfactant-associated proteins A, B, C, and D (SP-A, SP-C, SP-D). Evidence exists of a defect in the homeostatic mechanism of either the production of surfactant or the clearance by alveolar macrophages and the mucociliary elevator. A clear relationship has been demonstrated between PAP and impaired macrophage maturation or function, which might account for the high association with malignancies and unusual infections, eg, infection with Nocardia asteroides.

Studies of genetically altered mice ("knock-out mice") with targeted gene deletions for GM-CSF yielded animals with PAP-like disease. GM-CSF has been demonstrated to increase the effectiveness of alveolar macrophages in the catabolism of surfactant. Recent studies have demonstrated the presence of neutralizing autoantibodies against GM-CSF in patients with PAP. Also documented is that alveolar macrophages from some PAP patients have decreased levels of the transcription factor peroxisome proliferator-activated receptor–gamma (PPAR-gamma), which normalize after treatment with GM-CSF.^[4]

Frequency

United States

PAP has an estimated prevalence of 1 case per 100,000 population.

International

Frequency is believed to be similar to that in the United States, but notification systems do not exist.

Mortality/Morbidity

Mortality rates of as high as 30% within several years of disease onset have been reported previously, but the actual mortality rate may be less than 10%. Solitary pulmonary PAP is increasingly being seen and may resolve spontaneously over several months.

The natural history of secondary PAP depends on the underlying etiologic entity.

Race

Isolated studies have reported predominance in patients of Arabian origin, but no other definitive studies are available.

Sex

Incidence for males is 4 times higher than for females.

Age

Patients are typically aged 20-50 years at presentation.

Proceed to Clinical Presentation

Contributor Information and Disclosures

Author

Roger B Olade, MD, MPH Medical Director, Providence Health Group

Roger B Olade, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Sepracor None None

Ali Hmidi, MD Staff Physician, Department of Internal Medicine, Brooklyn Hospital Center, Cornell University

Disclosure: Nothing to disclose.

Oluwatoyin E Ijitola, MD, PhD, RN Dean and Professor, International University for Graduate Studies (IUGS)

Oluwatoyin E Ijitola, MD, PhD, RN is a member of the following medical societies: American Academy of Tropical Medicine, American College of Healthcare Executives, American Medical Association, American Society of Tropical Medicine and Hygiene, HIV Medicine Association of America, and International AIDS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Gregg T Anders, DO is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Timothy D Rice, MD Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

References

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