eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Alveolar Proteinosis: Follow-up

Author: Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Coauthor(s): Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland; Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Contributor Information and Disclosures

Updated: Aug 5, 2008

Follow-up

Further Inpatient Care

  • Admit patients for diagnostic workup and lung lavage.
  • For affected neonates, lung transplantation should be considered early.

Further Outpatient Care

  • Monitor for disease progression. Increasing symptoms may warrant further lung lavage. Vigorous lung physiotherapy may be helpful.
  • The optimal imaging modality for serial follow-up remains unclear. Lee et al (1997) concluded that, although HRCT findings are most closely correlated with pulmonary function, plain chest radiography provides sufficient information in conjunction with clinical findings and PFT.17

Inpatient & Outpatient Medications

  • Bronchodilators may be used if evidence of airway reactivity is present.
  • Mucolytics, including acetylcysteine, trypsin, and ambroxol, have all been used; their efficacy is unknown.
  • Recent data suggest that GM-CSF may be useful.
  • Although a high-calorie diet is essential, ensure that the carbohydrate load is not excessive because this may exacerbate respiratory difficulties by causing a high respiratory quotient and hence a high CO2 burden.
  • No medications are specifically contraindicated.

Transfer

  • Transfer to a tertiary center may be necessary for further diagnostic workup, supportive care ECMO, or lung transplantation.
  • In view of the rarity of this condition, consider early transfer to a tertiary level institution experienced in managing this condition.

Deterrence/Prevention

  • Smoking by, or around, the patient must be discouraged.

Complications

  • Death
  • Superinfection
  • Pulmonary fibrosis
  • Secondary amyloidosis

Prognosis

  • CAP: Without lung transplantation, mortality is almost inevitable in the neonatal age group.10
  • Acquired pulmonary alveolar proteinosis (PAP): Analysis of published data suggested an actuarial 5-year disease-specific survival rate of 88% ±5%. The 5-year survival rate for children younger than 5 years was 14% ±13%, although this rate represented data from 7 children.10 Many investigators have reported spontaneous remission in a select group of adults with acquired PAP. Seymour and Presneill (2002) reported 24 of 303 patients (7.9%) had spontaneous improvement.10 Whether this improvement led to true resolution of the disease and restoration of lung function and surfactant clearance was unclear.

Patient Education

  • Patients with PAP may benefit from postural drainage, but no data support this hypothesis.
  • Smoking near the patient must be discouraged.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize associated conditions, including immunodeficiency states, malignancy, and infections
  • Failure to offer genetic counseling to parents of an affected child
 


More on Alveolar Proteinosis

Overview: Alveolar Proteinosis
Differential Diagnoses & Workup: Alveolar Proteinosis
Treatment & Medication: Alveolar Proteinosis
Follow-up: Alveolar Proteinosis
References
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References

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

  2. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med. Dec 25 2003;349(26):2527-39. [Medline].

  3. deMello DE, Nogee LM, Heyman S, et al. Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency. J Pediatr. Jul 1994;125(1):43-50. [Medline].

  4. Goldstein LS, Kavuru MS, Curtis-McCarthy P, et al. Pulmonary alveolar proteinosis: clinical features and outcomes. Chest. Nov 1998;114(5):1357-62. [Medline].

  5. Nogee LM, Garnier G, Dietz HC, et al. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. Apr 1994;93(4):1860-3. [Medline].

  6. Knight DP, Knight JA. Pulmonary alveolar proteinosis in the newborn. Arch Pathol Lab Med. Jun 1985;109(6):529-31. [Medline].

  7. Coleman M, Dehner LP, Sibley RK, Burke BA, L'Heureux PR, Thompson TR. Pulmonary alveolar proteinosis: an uncommon cause of chronic neonatal respiratory distress. Am Rev Respir Dis. Mar 1980;121(3):583-6. [Medline]. [Full Text].

  8. Prakash UB, Barham SS, Carpenter HA, Dines DE, Marsh HM. Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc. Jun 1987;62(6):499-518. [Medline].

  9. Witty LA, Tapson VF, Piantadosi CA. Isolation of mycobacteria in patients with pulmonary alveolar proteinosis. Medicine (Baltimore). Mar 1994;73(2):103-9. [Medline].

  10. 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].

  11. Schumacher RE, Marrogi AJ, Heidelberger KP. Pulmonary alveolar proteinosis in a newborn. Pediatr Pulmonol. 1989;7(3):178-82. [Medline].

  12. Nogee LM, Dunbar AE 3rd, Wert S, Askin F, Hamvas A, Whitsett JA. Mutations in the surfactant protein C gene associated with interstitial lung disease. Chest. Mar 2002;121(3 Suppl):20S-21S. [Medline].

  13. Uchida K, Beck DC, Yamamoto T, et al. GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. N Engl J Med. Feb 8 2007;356(6):567-79. [Medline].

  14. Mahut B, Delacourt C, Scheinmann P, et al. Pulmonary alveolar proteinosis: experience with eight pediatric cases and a review. Pediatrics. Jan 1996;97(1):117-22. [Medline].

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

  16. Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know. Cleve Clin J Med. Dec 2001;68(12):977-8, 981-2, 984-5 passim. [Medline].

  17. Lee KN, Levin DL, Webb WR, et al. Pulmonary alveolar proteinosis: high-resolution CT, chest radiographic, and functional correlations. Chest. Apr 1997;111(4):989-95. [Medline].

  18. Albafouille V, Sayegh N, De Coudenhove S, et al. CT scan patterns of pulmonary alveolar proteinosis in children. Pediatr Radiol. Mar 1999;29(3):147-52. [Medline].

  19. Wang BM, Stern EJ, Schmidt RA, Pierson DJ. Diagnosing pulmonary alveolar proteinosis. A review and an update. Chest. Feb 1997;111(2):460-6. [Medline].

  20. 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. Feb 2001;163(2):524-31. [Medline].

  21. Kavuru MS, Sullivan EJ, Piccin R, et al. Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis. Am J Respir Crit Care Med. Apr 2000;161(4 Pt 1):1143-8. [Medline].

  22. Hamvas A, Cole FS, deMello DE, et al. Surfactant protein B deficiency: antenatal diagnosis and prospective treatment with surfactant replacement. J Pediatr. Sep 1994;125(3):356-61. [Medline].

  23. Claypool WD, Rogers RM, Matuschak GM. Update on the clinical diagnosis, management, and pathogenesis of pulmonary alveolar proteinosis (phospholipidosis). Chest. Apr 1984;85(4):550-8. [Medline].

  24. Parker LA, Novotny DB. Recurrent alveolar proteinosis following double lung transplantation. Chest. May 1997;111(5):1457-8. [Medline].

  25. Price A, Manson D, Cutz E, Dell S. Pulmonary alveolar proteinosis associated with anti-GM-CSF antibodies in a child: successful treatment with inhaled GM-CSF. Pediatr Pulmonol. Apr 2006;41(4):367-70. [Medline].

  26. Cho K, Nakata K, Ariga T, et al. Successful treatment of congenital pulmonary alveolar proteinosis with intravenous immunoglobulin G administration. Respirology. Jan 2006;11 Suppl:S74-7. [Medline].

  27. Anton HC, Gray B. Pulmonary alveolar proteinosis presenting with pneumothorax. Clin Radiol. Oct 1967;18(4):428-31. [Medline].

  28. Arora PL, Rogers RM, Mayock RL. Alveolar proteinosis. Experience with trypsin therapy. Am J Med. Jun 1968;44(6):889-99. [Medline].

  29. Ballard PL, Nogee LM, Beers MF, et al. Partial deficiency of surfactant protein B in an infant with chronic lung disease. Pediatrics. Dec 1995;96(6):1046-52. [Medline].

  30. Barraclough RM, Gillies AJ. Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. Thorax. Aug 2001;56(8):664-5. [Medline].

  31. Clague HW, Wallace AC, Morgan WK. Pulmonary interstitial fibrosis associated with alveolar proteinosis. Thorax. Nov 1983;38(11):865-6. [Medline].

  32. 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. May-Jun 1992;12(3):365-83. [Medline].

  33. Ganguli PC, Lynne-Davies P, Sproule BJ. Pulmonary alveolar proteinosis, bronchiectasis and secondary amyloidosis: a case report. Can Med Assoc J. Mar 4 1972;106(5):569 passim. [Medline].

  34. Gough J. Silicosis and alveolar proteinosis. Br Med J. Mar 11 1967;1(540):629. [Medline].

  35. Hamvas A. Surfactant protein B deficiency: insights into inherited disorders of lung cell metabolism. Curr Probl Pediatr. Oct 1997;27(9):325-45. [Medline].

  36. Hildebrand FL Jr, Rosenow EC 3d, Habermann TM, Tazelaar HD. Pulmonary complications of leukemia. Chest. Nov 1990;98(5):1233-9. [Medline].

  37. Hirakata Y, Kobayashi J, Sugama Y, Kitamura S. Elevation of tumour markers in serum and bronchoalveolar lavage fluid in pulmonary alveolar proteinosis. Eur Respir J. May 1995;8(5):689-96. [Medline].

  38. Honda Y, Kuroki Y, Shijubo N, et al. Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic pulmonary fibrosis and its clinical significance. Respiration. 1995;62(2):64-9. [Medline].

  39. Jansen HM, Zuurmond WW, Roos CM, et al. Whole-lung lavage under hyperbaric oxygen conditions for alveolar proteinosis with respiratory failure. Chest. Jun 1987;91(6):829-32. [Medline].

  40. Lin FC, Chen YC, Chang HI, Chang SC. Effect of body position on gas exchange in patients with idiopathic pulmonary alveolar proteinosis: no benefit of prone positioning. Chest. Mar 2005;127(3):1058-64. [Medline].

  41. Martinez-Lopez MA, Gomez-Cerezo G, Villasante C, et al. Pulmonary alveolar proteinosis: prolonged spontaneous remission in two patients. Eur Respir J. Mar 1991;4(3):377-9. [Medline].

  42. Nara M, Sano K, Ogawa H, et al. Serum antibody against granulocyte/macrophage colony-stimulating factor and KL-6 in idiopathic pulmonary alveolar proteinosis. Tohoku J Exp Med. Apr 2006;208(4):349-54. [Medline].

  43. Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol. 2004;66:601-23. [Medline].

  44. Parto K, Kallajoki M, Aho H, Simell O. Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients. Hum Pathol. Apr 1994;25(4):400-7. [Medline].

  45. Paschen C, Reiter K, Stanzel F, et al. Therapeutic lung lavages in children and adults. Respir Res. 2005;6:138. [Medline].

  46. Ranchod M, Bissell M. Pulmonary alveolar proteinosis and cytomegalovirus infection. Arch Pathol Lab Med. Mar 1979;103(3):139-42. [Medline].

  47. Samuels MP, Warner JO. Pulmonary alveolar lipoproteinosis complicating juvenile dermatomyositis. Thorax. Nov 1988;43(11):939-40. [Medline].

  48. Seymour JF, Dunn AR, Vincent JM, et al. Efficacy of granulocyte-macrophage colony-stimulating factor in acquired alveolar proteinosis. N Engl J Med. Dec 19 1996;335(25):1924-5. [Medline].

  49. Shah PL, Conway S, Scott SF, et al. A case-controlled study with dornase alfa to evaluate impact on disease progression over a 4-year period. Respiration. 2001;68(2):160-4. [Medline].

  50. Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax. Jan 2000;55(1):67-77. [Medline].

  51. Spock A. Long-term survival of paediatric patients with pulmonary alveolar proteinosis treated with lung lavage. Eur Respir J. Jun 2005;25(6):1127. [Medline].

  52. Stevens PA, Pettenazzo A, Brasch F, et al. Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene. Pediatr Res. Jan 2005;57(1):89-98. [Medline].

  53. Summers JE. Pulmonary alveolar proteinosis. Review of the literature with follow-up studies and report of two new cases. Calif Med. Jun 1966;104(6):428-36. [Medline].

  54. Sunderland WA, Campbell RA, Edwards MJ. Pulmonary alveolar proteinosis and pulmonary cryptococcosis in an adolescent boy. J Pediatr. Mar 1972;80(3):450-6. [Medline].

  55. Tsai WC, Lewis D, Nasr SZ, Hirschl RB. Liquid ventilation in an infant with pulmonary alveolar proteinosis. Pediatr Pulmonol. Oct 1998;26(4):283-6. [Medline].

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Further Reading

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Keywords

alveolar proteinosis, pulmonary alveolar proteinosis, PAP, respiratory failure, congenital alveolar proteinosis, CAP, secondary pulmonary alveolar proteinosis, pulmonary macrophage dysfunction, smoking, tobacco use, neonatal respiratory distress, respiratory distress syndrome, pneumonia, sepsis, failure to thrive, dyspnea, pneumothorax, lysinuric protein intolerance, Nocardia species, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, human immunodeficiency virus, HIV, Pneumocystis species, Cryptococcus species, cytomegalovirus, polycythemia, respiratory alkalosis, hyperventilation

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Contributor Information and Disclosures

Author

Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Anne E Stone, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland
David J Vaughan, MBBCh is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Jerry Zimmerman, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, Society for Pediatric Research, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Susanna A McColley, MD, Director of Cystic Fibrosis Center; Head, Division of Pulmonary Medicine; Associate Professor, Department of Pediatrics, Children's Memorial Medical Center of Chicago, Northwestern University
Susanna A McColley, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Sleep Disorders Association, and American Thoracic Society
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Consulting fee Consulting; Novartis Consulting fee Consulting; Altus Consulting fee Consulting; Axcan Scandi Consulting fee Consulting; Boston Scientific Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

 
 
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