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Pulmonary Alveolar Proteinosis Workup

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

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.[11, 12] Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

Recent studies have shown a correlation between the levels of some tumor markers such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) and severity of PAP.[13]

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.

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Imaging Studies

Chest radiography 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).[14, 15] PAP may also present as ground-glass opacity (GGO), mimicking carcinoma.[16] HRCT findings have been able to show several distinctive differences between exogenous lipoid pneumonia and PAP, which had previously only been distinguished pathologically.[17]

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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.

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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.

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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
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  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].

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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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