Pulmonary Alveolar Proteinosis Workup

  • Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Mar 16, 2011
 

Laboratory Studies

Serologic studies are generally not useful for pulmonary alveolar proteinosis (PAP). Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF.[7, 8] Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

The diagnosis can be made by BAL only if PAS staining is requested. Therefore, PAP is probably underdiagnosed.

Lung biopsy findings are classic for PAP. Alveoli are filled with nonfoamy material. Transbronchial biopsies are adequate, and open lung biopsy is not required.

Next

Imaging Studies

CXR in pulmonary alveolar proteinosis (PAP) shows bilateral perihilar infiltrates with consolidation in a "bat-wing" configuration, which may mimic pulmonary edema, although with a typical absence of cardiomegaly or pleural effusion. Unilateral involvement occurs occasionally, and lymphadenopathy is rarely present. Typically, changes progress over weeks to months into a diffuse reticulogranular pattern.

High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as "crazy paving." The crazy-paving pattern also can be observed in exogenous lipoid pneumonia, sarcoidosis, mucinous bronchoalveolar cell carcinoma, and acute respiratory distress syndrome (ARDS).[9, 10] HRCT findings have been able to show several distinctive differences between exogenous lipoid pneumonia and PAP, which had previously only been distinguished pathologically.[11]

Previous
Next

Procedures

Bronchoscopy with transbronchial biopsy and BAL may be helpful. Transbronchial biopsies of affected lung segments, coupled with findings on BAL, are sufficient to make the diagnosis. Use PAS reagent for BAL. Bronchoalveolar lavage fluid appears "milky." Papanicolaou staining may reveal green and orange globules that are diagnostic for PAP. Electron microscopy of BAL may reveal characteristic multilamellar structures.

Transbronchial biopsy may increase the yield. Surgical lung biopsy rarely is necessary for definitive diagnosis.

Previous
Next

Histologic Findings

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material. Electron microscopy of the material in the alveoli shows multilamellated structures and membranous vesicles.

Previous
Proceed to Treatment & Management
 
 
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

  1. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med. Jun 5 1958;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. Feb 2010;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. Dec 2003;29(6):677-82. [Medline].

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

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

  7. 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. Jul 2005;12(7):821-4. [Medline].

  8. 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. Apr 2000;161(4 Pt 1):1294-9. [Medline].

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

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

  11. 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. May 2010;51(4):407-12. [Medline].

  12. 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. Feb 18 2010;[Medline].

  13. 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. Aug 2004;9(3):419-22. [Medline].

  14. Anders P. Pulmonary Alveolar Proteinosis. In: Fishman AP, Elia JA, Fishman JA, Grippi MA, Kaiser LR, Senior RM, eds. Fishman's Pulmonary Diseases and Disorders. 3rd ed. New York, NY: McGraw-Hill; 1998:1223-9.

  15. Carey B, Trapnell BC. The molecular basis of pulmonary alveolar proteinosis. Clin Immunol. Mar 24 2010;[Medline].

  16. Crocker HL, Pfitzner J, Doyle IR, Hague WM, Smith BJ, Ruffin RE. Pulmonary alveolar proteinosis: two contrasting cases. Eur Respir J. Feb 2000;15(2):426-9. [Medline].

  17. 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. Mar 1 2010;181(5):458-64. [Medline].

  18. Ioachimescu OC, Kavuru MS. Pulmonary alveolar proteinosis. Chron Respir Dis. 2006;3(3):149-59. [Medline].

  19. Kitamura T, Uchida K, Tanaka N, Tsuchiya T, Watanabe J, Yamada Y, et al. Serological diagnosis of idiopathic pulmonary alveolar proteinosis. Am J Respir Crit Care Med. Aug 2000;162(2 Pt 1):658-62. [Medline].

  20. Presneill JJ, Nakata K, Inoue Y, Seymour JF. Pulmonary alveolar proteinosis. Clin Chest Med. Sep 2004;25(3):593-613, viii. [Medline].

  21. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. Jul 15 2002;166(2):215-35. [Medline].

  22. Venkateshiah SB, Thomassen MJ, Kavuru MS. Pulmonary alveolar proteinosis. Clinical manifestations and optimal treatment strategies. Treat Respir Med. 2004;3(4):217-27. [Medline].

 
Previous
Next
 
A periodic acid-Schiff histochemical stain of transbronchial biopsy: Alveolar spaces contain considerable amounts of granular material.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.