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VOLUME 1 , ISSUE 1 ( January-June, 2018 ) > List of Articles


Pulmonary Alveolar Proteinosis—Where Do We Stand?

Mandeep K Sodhi, S Narayanan

Keywords : Pulmonary alveolar proteinosis (PAP) review, Surfactant, Whole lung lavage.

Citation Information : Sodhi MK, Narayanan S. Pulmonary Alveolar Proteinosis—Where Do We Stand?. Journal of Medical Academics 2018; 1 (1):53-57.

DOI: 10.5005/jp-journals-10070-0010

License: NA

Published Online: 01-04-2018

Copyright Statement:  NA


Aim: This review intends to recapitulate the knowledge about pulmonary alveolar proteinosis (PAP) and insight into the advances in the pathogenesis and treatment of this condition. Background: A PAP is a seldom occurring disease with numerous possible etiologies. Review results: The disease has an insidious onset and the opinion is mostly delayed due to the fact that patients present late when there is abundant surfactant assimilation in alveoli to diminish gas exchange and cause dyspnea. An appropriate history, typical chest radiographic and high resolution computed tomography (HRCT) findings together with characteristic b ronchoalveolar lavage (BAL) fluid help to elucidate the diagnosis in most cases. However, transbronchial lung biopsy (TBLB) or open lung biopsy may be rarely needed for difficult to diagnose cases. Treatment is needed for patients with symptomatic disease and whole lung lavage is the treatment of choice. Conclusion: A PAP is a rare disease entity with variable natural history. The clinical course varies from respiratory failure to spontaneous resolution. Clinical significance: This review will help to furnish an outline of the various aspects of this disease in light of fresh scientific advancements in the pathogenesis and treatment of this condition. Knowledge about the disease will serve to better define the role of alternative and new therapies for the same.

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  1. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med 1958;258:1123-1142.
  2. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002;166:215-235.
  3. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003;349:2527-2539.
  4. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of autoimmune pulmonary alveolar proteinosis patients in Japan. Am J Respir Crit Care Med 2008;177:752–762.
  5. Hadda V, Tiwari P, Madan K, etal. Pulmonary alveolar proteinosis: Experience from a tertiary care center and systematic review of Indian literature. Lung India 2016;33:626-634.
  6. Hwang JA, Song JH, Kim JH et al. Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey. BMC Pulm Med. 2017 Nov 21;17(1):147
  7. Goldstein LS, Kavuru MS, Curtis-McCarthy P, et al. Pulmonary alveolar proteinosis: clinical features and outcomes. Chest 1998;114:1357-1362.
  8. Prakash UB, Barham SS, Carpenter HA, et al. Pulmonary alveolarphospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 1987;62:499-518.
  9. Wasserman K, Mason GR. Pulmonary alveolar proteinosis. In: Murray JF, Nadel JA, editors Textbook of respiratory medicine, 5th ed. Philadelphia: Saunders; 1994. p. 1933– 1946
  10. Uchida K, Nakata K, Trapnell BC, et al. High-affinity autoantibodies specifically eliminate granulocyte-macrophagecolony- stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Blood 2004;103(3):1089-1098.
  11. Torrents D, Mykkänen J, Pineda M, et al. Identification of SLC7A7, encoding y_LAT-1, as the lysinuric protein intolerance gene. Nat Genet 1999;21:293-296.
  12. Buechner HA, Ansari A. Acute silico-proteinosis: a new pathologicvariant of acute silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 1969;55:274–284.
  13. Fisher M, Roggli V, Merten D, et al. Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation. Pediatr Pathol 1992;12(3):365-383.18
  14. Hildebrand FL Jr, Rosenow ECI, Habermann TM, et al. Pulmonary complications of leukemia. Chest 1990;98:1233-1239.
  15. Nogee LM, de Mello DE, Dehner LP, et al. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993;328(6):406-410.
  16. Dirksen U, Hattenhorst U, Schneider P, et al. Defective expression of granulocyte-macrophage-colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. Blood 1998;92(4):1097-1103.
  17. Teja K, Cooper PH, Squires JE, et al. Pulmonary alveolar proteinosis in four siblings. N Engl J Med 1981;305(23):1390- 1392.
  18. Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 2010;61:105-119.
  19. Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granulocyte-macrophage-colony-stimulating factor in pulmonary homeostasis. Science 1994;264:713-716.
  20. Haagsman H.P, Diemel R.V. Surfactant-associated proteins: functions and structural variation. Com Biochem Physiol A Mol Integr Physiol 2001;129:91-108.
  21. Burgess AW, Camakaris J, Metcalf D. Purification and properties of colony-stimulating factor from mouse lungconditioned medium. J Biol Chem 1977;252(6):1998-2003
  22. Bonfield TL, Raychaudhuri B, Malur A, et al. PU. 1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage-colony-stimulating factor. Am J Physiol Lung Cell Mol Physiol 2003;285(5):L1132-1136.
  23. Shibata Y, Berclaz PY, Chroneos ZC, et al. GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1. Immunity 2001;15:557-567.
  24. Uchida K, Beck DC, Yamamoto T, et al. GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. N Engl J Med 2007;356:567-79.
  25. Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know. Cleve Clin J Med 2001;68(12):977-978.
  26. Selecky PA, Wasserman K, Benfield JR, et al. The clinical and physiological effect of whole-lung lavage in pulmonary alveolar proteinosis: a ten-year experience. Ann Thorac Surg 1977;24(5):451-461.
  27. Rubin E, Weisbrod GL, Sanders DE. Pulmonary alveolar proteinosis: relationship to silicosis and pulmonary infection. Radiology 1980;135(1):35-41
  28. Lee KN, Levin DL, Webb WR, et al. Pulmonary alveolarproteinosis: high-resolution CT, chest radiographic, and functional correlations. Chest1997;111:989-95.
  29. Johkoh T, Itoh H, Muller N, et al. Crazy-paving appearance at thin-section CT:spectrum of disease and pathologic findings. Radiology 1999;211:155-60.
  30. Martin RJ, Coalson JJ, Rogers RM, et al. Pulmonary alveolar proteinosis: the diagnosis by segmental lavage. Am Rev Respir Dis 1980;121(5):819-825.
  31. Maygarden SJ, Iacocca MV, Funkhouser WK, et al. Pulmonaryalveolar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid. Diagn Cytopathol 2001;24(6):389-395.
  32. Levin DC, Wicks AB, Ellis JH Jr. Transbronchiallungbiopsy via the fiberoptic bronchoscope. Am Rev Respir Dis1974;110:4-12.
  33. Lin FC, Chang GD, Chern MS, et al. Clinicalsignificance of anti-GM-CSF antibodies in idiopathicpulmonary alveolar proteinosis. Thorax. 2006;61(6):528e534.
  34. Du Bois RM, McAllister WA, Branthwaite MA. Alveolar proteinosis: diagnosis and treatment over a 10-year period. Thorax 1983;38(5):360-363.
  35. Gale ME, Karlinsky JB, Robins AG. Bronchopulmonary lavage in pulmonary alveolar proteinosis: chest radiograph observations. AJR Am J Roentgenol 1986;146(5):981- 985.
  36. Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax 2000;55:67-77.
  37. Trapnell B.C, Suzuki T. Pulmonary Alveolar Proteinosis Syndrome. In: Grippi MA, Elias JA, Fishman JA., et al, ed. Fishman's Pulmonary Diseases and Disorders. 5th edition. United States: McGraw Hill Education; 2015. p: 2243-2260
  38. Seymour JF, Presneill JJ, Schoch OD, et al. Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis. Am J Respir Crit Care Med 2001;163:524-531.
  39. Luisetti M, Rodi G, Perotti C, et al. Plasmapheresis fortreatment of pulmonary alveolar proteinosis. Eur Respir J2009;33:1220-2.
  40. Borie R, Debray MP, Laine C, et al. B. Rituximabtherapy in autoimmune pulmonary alveolar proteinosis. Eur Respir J 2009;33(6):1503-1506.
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