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Pediatric Alveolar Proteinosis Clinical Presentation

  • Author: Danielle M Goetz, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
 
Updated: Dec 21, 2015
 

History

Predominant symptoms depend on the patient's age at presentation and include neonatal respiratory distress, progressive exertional dyspnea with insidious onset, cough, fatigue, low-grade fever, and weight loss.[18] Chest pain and hemoptysis occur less commonly, especially if secondary infection is present.[1] Note the following:

  • Neonatal respiratory distress: Patients with the congenital form of pulmonary alveolar proteinosis (PAP) present with progressive respiratory failure and marked hypoxemia shortly after birth. [11] The condition is initially indistinguishable from other causes of neonatal respiratory distress, including infant respiratory distress syndrome, congenital pneumonia, sepsis, and some forms of congenital heart disease. Patients were typically born after normal, uncomplicated pregnancies. [14, 15, 21] Prolonged ventilator dependence is ascribed to slow resolution of the initial illness, persisting atelectasis, or pneumonia.
  • Dyspnea: In children and young adults, the most consistent finding is shortness of breath upon exertion. Case series showed that the prevalence of dyspnea in adults with PAP was 50-80%. [10, 17, 18] In the initial stages of illness, dyspnea may manifest as diminished exercise tolerance.
  • Cough: Patients may have associated mild cough that occasionally produces thick sputum or solid material. As many as 80% of adults report having a cough. [10]
  • Failure to thrive: Although failure to thrive is obviously more common in young children and infants than in others, poor weight gain, poor appetite, and malaise are often present in older children as well. Patients often have a decreased level of activity and difficulty feeding. [18]
  • Chest pain: Chest pain is uncommon, occurring in 10-20% of patients. [10]
  • Fever: Fever is unusual and may signify superinfection. [10]
  • Unusual presentations: Rare patients present with pneumothorax or hemoptysis. Another uncommon presentation is a child with persisting infiltrates on chest radiography.
  • Family history: Because the congenital form is transmitted as an autosomal recessive disease, families may report a history of a previous child with neonatal respiratory distress. [11]
  • Risk factors: Young adults may have risk factors, such as a smoking history or exposure to metallic dust. The patient's history may also suggest predisposing conditions, such as immunodeficiency, malignancy, or autoimmune disease. [18]
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Physical

PAP has been termed a silent pulmonary condition in which the auscultatory findings are usually relatively benign compared with the radiographic evidence of disease.

  • Physical examination may reveal evidence of failure to thrive or poor weight gain. Other findings include signs of a predisposing disease process (eg, malignancy, infection, immunodeficiency).
  • Digital clubbing is a late sign and is present in a small percentage of patients. [1, 10]
  • Examination of the respiratory system may reveal crackles, clubbing, and cyanosis. Most often, chest findings are unremarkable. [10]
  • In newborns with CAP, the clinical presentation is marked by respiratory failure rapidly leading to death. [11]
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Causes

Three types of PAP have been described: congenital (genetic), secondary (acquired), and idiopathic (primary). All lead to impaired clearance of surfactant from the alveolar space.

Congenital (genetic) PAP

Congenital (genetic) PAP describes a group of disorders caused by mutations in the genes that encode for surfactant protein B or C, ATP-binding cassette 3 (ABCA3), NK2 homeobox 1 (NKX2-1), or the beta chain of the receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF).[12, 18] There has also been described a mutation in SLC7A7, which leads to lysinuric protein intolerance and PAP.[12]

Most cases of congenital or genetic PAP are transmitted in an autosomal recessive pattern.[11]

The most common cause of congenital PAP is homozygosity for a frame-shift mutation in the surfactant protein B (SP-B) gene that leads to unstable SP-B mRNA, decreased protein levels, and subsequent deficient processing of SP-C.[11]

Mutations in the SP-C gene can also lead to neonatal respiratory distress.[22]

Molecular genetic heterogeneity among infants with congenital SP-B deficiency has been reported. For example, patients heterozygous for the SP-B gene mutation have been found to have normal pulmonary function as of their fourth decade of life.[18]

Other cases of congenital PAP have no known abnormalities in SP-B but are associated with disturbances in the alpha chain of the GM-CSF receptor, encoded by CSF2RA, or in the beta chain of the GM-CSF receptor, encoded by CSF2RB[12]

Lysinuric protein intolerance is an autosomal recessive disease caused by mutation of SLC7A7, leading to defective transport of cationic amino acids at the membrane of epithelial cells in the intestine and kidney. The clinical picture involves failure to thrive and gastrointestinal symptoms, including pancreatic insufficiency, as well as renal insufficiency. There are excessive amounts of dibasic amino acids (arginine, lysine, and ornithine) in the urine. Pulmonary manifestations can include PAP and respiratory insufficiency.[12]

Secondary (acquired) PAP

Secondary development of PAP has numerous underlying causes, usually systemic inflammatory disease or hematologic disorders and cancers.[18, 23]

Other inciting agents for PAP include inhaled precipitants such as aluminum, titanium, silicates, cement dust, and insecticides.[3]

The etiology is unknown, although some have speculated that the small particles may stimulate excessive secretion of surfactant, impair macrophage clearance, or both.

Autoimmune PAP

Autoimmune (formerly known as idiopathic, or primary PAP), which accounts for more than 90% of all cases of PAP, is due to the presence of anti-GM-CSF antibodies. These antibodies prevent the binding of GM-CSF to GM-CSF receptors on alveolar macrophages.[1, 12, 18]

Research with GM-CSF knockout mice in 1994 revealed decreased surfactant clearance and the development of a condition similar to human PAP.

The GM-CSF knockout mice had normal hematopoiesis but impaired surfactant clearance by alveolar macrophages.

This first suggested that intracellular signaling initiated by the binding of GM-CSF to its receptor is necessary for pulmonary surfactant homeostasis.[23]

GM-CSF is a cytokine that stimulates proliferation and differentiation of neutrophil, monocyte, and macrophage hematopoietic cells in vitro when it engages with its receptor. The GM-CSF receptor comprises a specific alpha chain and common beta chain. Alveolar macrophages and alveolar type II epithelial cells express this beta chain.[1]

The interruption of GM-CSF signaling leads to failure of PU.1-mediated terminal differentiation of alveolar macrophages, impaired catabolism of surfactant, and progressive accumulation in structurally normal alveoli.[24]

Trapnell et al found GM-CSF – neutralizing autoantibody in serum and in BAL fluid obtained from humans with acquired PAP.[1] They suggested that the antibody inhibits GM-CSF activity and leads to the accumulation of proteinaceous fluid in the alveoli. This antibody has not been identified in patients with congenital or secondary PAP.

Other considerations

Various microorganisms are described in association with PAP, including Nocardia species, Mycobacterium tuberculosis and Mycobacterium avium-intracellulare, human immunodeficiency virus (HIV), Pneumocystis species, Cryptococcus species, and cytomegalovirus.[18]

Recent research examining host defense in GM-CSF knockout mice demonstrated the restoration of immune function with return to GM-CSF expression. This finding supports the conclusion that GM-CSF plays a role in local immunity in the lung.[1, 25]

Recent research examining therapy with GM-CSF by inhaled or subcutaneous route in patients with autoimmune PAP suggests benefit.[24]

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Contributor Information and Disclosures
Author

Danielle M Goetz, MD Clinical Assistant Professor of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Women and Children's Hospital of Buffalo; Associate Cystic Fibrosis Center Director, Director of Pediatric Resident and Medical Student Rotation in Pediatric Pulmonology at Women's and Children's Hospital of Buffalo

Danielle M Goetz, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Charles Callahan, DO Professor, Chief, Department of Pediatrics and Pediatric Pulmonology, Tripler 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, Christian Medical and Dental Associations

Disclosure: Nothing to disclose.

Chief Editor

Girish D Sharma, MD, FCCP, FAAP Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush Children's Hospital, Rush University Medical Center

Girish D Sharma, MD, FCCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Additional Contributors

Michael R Bye, MD Professor of Clinical Pediatrics, State University of New York at Buffalo School of Medicine; Attending Physician, Pediatric Pulmonary Division, Women's and Children's Hospital of Buffalo

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Susanna A McColley, MD Professor of Pediatrics, Northwestern University, The Feinberg School of Medicine; Director of Cystic Fibrosis Center, Head, Division of Pulmonary Medicine, Children's Memorial Medical Center of Chicago

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, American Thoracic Society

Disclosure: Received honoraria from Genentech for speaking and teaching; Received honoraria from Genentech for consulting; Partner received consulting fee from Boston Scientific for consulting; Received honoraria from Gilead for speaking and teaching; Received consulting fee from Caremark for consulting; Received honoraria from Vertex Pharmaceuticals for speaking and teaching.

Acknowledgements

Michael Bye, MD, Professor of Clinical Pediatrics, Division of Pediatric Pulmonology, Women & Children's Hospital of Buffalo and State University of New York at Buffalo School of Medicine

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

  2. [Guideline] Leth S, Bendstrup E, Vestergaard H and Hilberg O. Autoimmune pulmonary alveolar proteinosis: treatment options in year 2013. Respirology. 2013. 18:82-91.

  3. Patel SM, Sekuguchi H, Reynold J and Krowks M. Pulmonary alveolar proteinosis. Canadian Respiratory Journal. 2012. 19:243-45.

  4. Raj D, Bhutia TD, Mathur S, Kabra SK, Lodha R. Pulmonary Alveolar Proteinosis Secondary to Pneumocystis jiroveci Infection in an Infant with Common Variable Immunodeficiency. Indian J Pediatr. 2013 May 5. [Medline].

  5. Hammami S, Harrathi K, Lajmi K, Hadded S, Ben Meriem C, Guédiche MN. Congenital pulmonary alveolar proteinosis. Case Rep Pediatr. 2013. 2013:764216. [Medline]. [Full Text].

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

  7. 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. 1994 Jul. 125(1):43-50. [Medline].

  8. Enaud L, Hadchouel A, Coulomb A, Berteloot L, Lacaille F, Boccon-Gibod L, et al. Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?. Orphanet J Rare Dis. 2014 Jun 14. 9:85. [Medline].

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

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

  11. 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. 1994 Apr. 93(4):1860-3. [Medline].

  12. Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, et al. Pulmonary alveolar proteinosis. European Respiratory Reviews. 2011. 20:98-107.

  13. Carey B & Trapnell B. Molecular basis of pulmonary alveolar proteinosis. Clinical Immunology. 2010. 135:223-25. [Full Text].

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

  15. 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. 1980 Mar. 121(3):583-6. [Medline]. [Full Text].

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

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

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

  19. Inoue Y et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. American Journal of Respiratory and Critical Care Medicine. 2008. 177:752-62.

  20. Tabatabaei SA, Karimi A, Tabatabaei SR, Radpay B, Jadali F, Shiva F, et al. Pulmonary alveolar proteinosis in children: a case series. J Res Med Sci. 2010 Mar. 15(2):120-4. [Medline]. [Full Text].

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

  22. 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. 2002 Mar. 121(3 Suppl):20S-21S. [Medline].

  23. Doerschuk CM. Pulmonary Alveolar Proteinosis- Is Host Defense Awry?. N Engl J Med. Feb 2007. 356:547-49.

  24. Khan A, Agarwal R, and Aggarwal A. Effectiveness of granulocyte-macrophage colony-stimulating factor therapy in autoimmune pulmonary alveolar proteinosis. Chest. 2012. 141:1273-83.

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

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

  27. Bonella F, Ohshimo S, Miaotian C, Griese M, Guzman J and Costable U. Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis. Orphanet Journal of Rare Diseases. 2013. 2013:[Full Text].

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

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

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

  31. Griese M, Ripper J, Sibbersen A, Lohse P, Lohse P, Brasch F, et al. Long-term follow-up and treatment of congenital alveolar proteinosis. BMC Pediatr. 2011 Aug 17. 11:72. [Medline]. [Full Text].

  32. 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 Feb. 163(2):524-31. [Medline].

  33. 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. 2000 Apr. 161(4 Pt 1):1143-8. [Medline].

  34. Malur A, Kavuru M, Marshall I, Barna B, Huizar I, Karnekar R, et al. Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis. Respiratory Research. 2012. 13:46. [Full Text].

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

  36. Lingadevaru H, Romano MA, Fauman K, Cooley E, Annich GM, Cornell TT. Challenges during repeat extracorporeal life support in a patient with pulmonary alveolar proteinosis. ASAIO J. 2011 Sep-Oct. 57(5):473-4. [Medline].

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

  38. DiFusco LA, Verma RK. Whole-lung lavage for pediatric patients with pulmonary alveolar proteinosis. AORN J. 2013 Jul. 98(1):50-67; quiz 68-70. [Medline].

  39. Badiozaman R, Tahereh P, Shideh D, Mohammadreza B, Ahmadreza A, Seyyedahmad T. Whole lung lavage of nine children with pulmonary alveolar proteinosis: experience in a tertiary lung center. Iran J Pediatr. 2013 Feb. 23(1):95-9. [Medline]. [Full Text].

  40. Gonçalves BM, Teixeira VC, Bittencourt PF. Anesthesia for lung lavage in pediatric patient with pulmonary alveolar proteinosis. Rev Bras Anestesiol. 2012 Mar-Apr. 62(2):269-73. [Medline].

  41. Wilson CA, Wilmshurst SL, Black AE. Anesthetic techniques to facilitate lung lavage for pulmonary alveolar proteinosis in children-new airway techniques and a review of the literature. Paediatr Anaesth. 2015 Jun. 25 (6):546-53. [Medline].

  42. Reiter K, Schoen C, Griese M & Nicolai T. Whole-lung lavage in infants and children with pulmonary alveolar proteinosis. Pediatric Anesthesia. 2010. 20:1118-1123.

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

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

  45. 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. 2006 Apr. 41(4):367-70. [Medline].

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

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

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

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

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

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

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

  53. 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 May-Jun. 12(3):365-83. [Medline].

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

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

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

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

  58. 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. 1995 May. 8(5):689-96. [Medline].

  59. 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].

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

  61. 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. 2000 Aug. 162(2 Pt 1):658-62. [Medline].

  62. 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. 2005 Mar. 127(3):1058-64. [Medline].

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

  64. 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. 2006 Apr. 208(4):349-54. [Medline].

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

  66. 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. 1994 Apr. 25(4):400-7. [Medline].

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

  68. Paschen C, Reiter K, Stanzel F, Teschler H and Griese M. Therapeutic lung lavages in children and adults. Respiratory Research. November 2005. 6:138. [Full Text].

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

  70. Santamaria F, Brancaccio G, Parenti G et al. Recurrent fatal pulmonary alveolar proteinosis after heart-lung transplantation in a child wiht lysinuric protein intolerance. Journal od Pediatrics. 2004. 145:268-72.

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

  72. 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].

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

  74. 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. 2005 Jan. 57(1):89-98. [Medline].

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

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

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

  78. Berteloot L, Taam RA, Emond-Gonsard S, Mamou-Mani T, Lambot K, Grévent D, et al. Primary pulmonary alveolar proteinosis: computed tomography features at diagnosis. Pediatr Radiol. 2014 Jul. 44 (7):795-802. [Medline].

 
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