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Pulmonary Alveolar Proteinosis

  • Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Dec 17, 2015
 

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 tranA 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).

PAP is related to granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies and GM-CSF deficiency.

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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-B, 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 escalator. A  relationship has been demonstrated between PAP and impaired macrophage maturation or function, which accounts for the 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  increases 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]

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Epidemiology

Frequency

United States

PAP has an estimated prevalence of 1 case per 100,000 population, but is probably underreported.

International

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

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.

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Contributor Information and Disclosures
Author

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

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

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, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

References
  1. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med. 1958 Jun 5. 258(23):1123-42. [Medline].

  2. Griese M, Brasch F, Aldana VR, Cabrera MM, Goelnitz U, Ikonen E, et al. Respiratory disease in Niemann-Pick type C2 is caused by pulmonary alveolar proteinosis. Clin Genet. 2010 Feb. 77(2):119-30. [Medline].

  3. Xue Y, Han Y, Li T, Chen S, Zhang J, Pan J, et al. Pulmonary alveolar proteinosis as a terminal complication in a case of myelodysplastic syndrome with idic(20q-). Acta Haematol. 2010. 123(1):55-8. [Medline].

  4. Bonfield TL, Farver CF, Barna BP, Malur A, Abraham S, Raychaudhuri B, et al. Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis. Am J Respir Cell Mol Biol. 2003 Dec. 29(6):677-82. [Medline].

  5. Cummings KJ, Donat WE, Ettensohn DB, Roggli VL, Ingram P, Kreiss K. Pulmonary alveolar proteinosis in workers at an indium processing facility. Am J Respir Crit Care Med. 2010 Mar 1. 181(5):458-64. [Medline]. [Full Text].

  6. Cummings KJ, Nakano M, Omae K, et al. Indium lung disease. Chest. 2012 Jun. 141(6):1512-21. [Medline]. [Full Text].

  7. Cummings KJ, Donat WE, Ettensohn DB, Roggli VL, Ingram P, Kreiss K. Pulmonary alveolar proteinosis in workers at an indium processing facility. Am J Respir Crit Care Med. 2010 Mar 1. 181(5):458-64. [Medline].

  8. Wardwell NR Jr, Miller R, Ware LB. Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug. Respirology. 2006 Sep. 11(5):663-5. [Medline].

  9. Suzuki T, Sakagami T, Young LR, et al. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. 2010 Nov 15. 182(10):1292-304. [Medline]. [Full Text].

  10. Carey B, Trapnell BC. The molecular basis of pulmonary alveolar proteinosis. Clin Immunol. 2010 May. 135(2):223-35. [Medline]. [Full Text].

  11. Bonfield TL, John N, Barna BP, Kavuru MS, Thomassen MJ, Yen-Lieberman B. Multiplexed particle-based anti-granulocyte macrophage colony stimulating factor assay used as pulmonary diagnostic test. Clin Diagn Lab Immunol. 2005 Jul. 12(7):821-4. [Medline].

  12. Carraway MS, Ghio AJ, Carter JD, Piantadosi CA. Detection of granulocyte-macrophage colony-stimulating factor in patients with pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2000 Apr. 161(4 Pt 1):1294-9. [Medline].

  13. Fang SC, Lu KH, Wang CY, Zhang HT, Zhang YM. Elevated tumor markers in patients with pulmonary alveolar proteinosis. Clin Chem Lab Med. 2013 Jan 11. 1-6. [Medline].

  14. Godwin JD, Müller NL, Takasugi JE. Pulmonary alveolar proteinosis: CT findings. Radiology. 1988 Dec. 169(3):609-13. [Medline].

  15. Murayama S, Murakami J, Yabuuchi H, Soeda H, Masuda K. "Crazy paving appearance" on high resolution CT in various diseases. J Comput Assist Tomogr. 1999 Sep-Oct. 23(5):749-52. [Medline].

  16. Sunadome H, Nohara J, Noguchi T, Matsui C, Kono T, Terada Y. [A case of pulmonary alveolar proteinosis that showed solitary ground-glass opacity in the subpleural area]. Nihon Kokyuki Gakkai Zasshi. 2010 Jul. 48 (7):516-9. [Medline].

  17. Choi HK, Park CM, Goo JM, Lee HJ. Pulmonary alveolar proteinosis versus exogenous lipoid pneumonia showing crazy-paving pattern: Comparison of their clinical features and high-resolution CT findings. Acta Radiol. 2010 May. 51(4):407-12. [Medline].

  18. Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, et al. Inhaled Granulocyte/Macrophage-Colony Stimulating Factor as Therapy of Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med. 2010 Feb 18. [Medline].

  19. Hasan N, Bagga S, Monteagudo J, Hirose H, Cavarocchi NC, Hehn BT, et al. Extracorporeal membrane oxygenation to support whole-lung lavage in pulmonary alveolar proteinosis: salvage of the drowned lungs. J Bronchology Interv Pulmonol. 2013 Jan. 20(1):41-4. [Medline].

  20. Abdul Rahman JA, Moodley YP, Phillips MJ. Pulmonary alveolar proteinosis associated with psoriasis and complicated by mycobacterial infection: successful treatment with granulocyte-macrophage colony stimulating factor after a partial response to whole lung lavage. Respirology. 2004 Aug. 9(3):419-22. [Medline].

  21. Rosen LB, Freeman AF, Yang LM, et al. Anti-GM-CSF Autoantibodies in Patients with Cryptococcal Meningitis. J Immunol. 2013 Apr 15. 190(8):3959-66. [Medline].

  22. Trapnell BC, Suzuki T. Pulmonary Alveolar Proteinosis. Fishman AP, Elia JA, Fishman JA, Grippi MA, Kotloff R, Senior RM, Pack A, eds. Fishman's Pulmonary Diseases and Disorders. 5th ed. New York, NY: McGraw-Hill Educational; 2015. 1028-37.

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