Long-term follow-up and treatment of congenital alveolar proteinosis

BMC Pediatrics

Andreas Hector³  Karl Reiter³  Thomas Nicolai³  Judith Glöckner-Pagel³  Carola Schön³  Oliver J Muensterer¹  Bianca Schaub³  Asli Pamir³  Andrea Schams³  Frank Brasch²  Peter Lohse⁴  Pia Lohse⁴  Anke Sibbersen³  Jan Ripper³  Matthias Griese³ 

[1] Weill-Cornell Medical Center, Division of Pediatric Surgery, New York, NY, USA;Institute for Pathology, Bielefeld, Germany;Dr. von Haunersches Kinderspital, University of Munich, Munich, Germany;Department of Clinical Chemistry-Großhadern, University of Munich, Munich, Germany

关键词: stop codon;    genetic defect;    GM-CSF-R alpha;    therapeutic lung lavage;    pulmonary alveolar proteinosis;   

Others  :  1172137
DOI  :  10.1186/1471-2431-11-72

 received in 2011-03-28, accepted in 2011-08-17,  发布年份 2011

【 摘 要 】

Background

Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP) due to mutations in the GM-CSF receptor are not well known.

Case presentation

A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child.

Conclusions

The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

【 授权许可】

   
2011 Griese et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Trapnell BC, Whitsett JA, Nakata K: Pulmonary alveolar proteinosis. N Engl J Med 2003, 349:2527-2539.
• [2]Seymour JF, Presneill JJ: Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Resp Crit Care Med 2002, 166:215-235.
• [3]Nishinakamura R, Nakayama N, Hirabayashi Y, Inoue T, Aud D, McNeil T, et al.: Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal. Immunity 1995, 2:211-222.
• [4]Dranoff G, Crawford AD, Sadelain M, Ream B, Rashid A, Bronson RT, et al.: Involvement of Granulocyte-Macrophage Colony-Stimulating Factor in Pulmonary Homeostasis. Science 1994, 264:713-716.
• [5]Uchida K, Nakata K, Trapnell BC, Terakawa T, Hamano E, Mikami A, et al.: High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Blood 2004, 103:1089-1098.
• [6]Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, et al.: Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med 2008, 205:2703-2710.
• [7]Martinez-Moczygemba M, Doan ML, Elidemir O, Fan LL, Cheung SW, Lei JT, et al.: Pulmonary alveolar proteinosis caused by deletion of the GM-CSFR alpha gene in the X chromosome pseudoautosomal region 1. J Exp Med 2008, 205:2711-2U19.
• [8]Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, et al.: Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med 2010, 182:1292-1304.
• [9]Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, et al.: Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. J Med Genet 2010.
• [10]Nogee L, Dunbar AE III, Wert S, Askin F, Hamvas A, Whitsett JA: Mutations in the surfactant protein C gene associated with interstitial lung disease. Chest 2002, 121:20S-21S.
• [11]Nogee LM, de Mello DE, Dehner LP, Colten HR: Brief-report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993, 328:406-410.
• [12]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, 77:119-130.
• [13]Ceruti M, Rodi G, Stella GM, Adami A, Bolongaro A, Baritussio A, et al.: Successful whole lung lavage in pulmonary alveolar proteinosis secondary to lysinuric protein intolerance: a case report. Orphanet J Rare Dis 2007., 2
• [14]Reiter K, Schoen C, Griese M, Nicolai T: Whole-lung lavage in infants and children with pulmonary alveolar proteinosis. Pediatr Anesth 2010, 20:1118-1123.
• [15]Paschen C, Reiter K, Stanzel F, Teschler H, Griese M: Therapeutic lung lavages in children and adults. Respir Res 2005, 6:138. BioMed Central Full Text
• [16]Tsai WC, Lewis D, Nasr SZ, Hirschl RB: Liquid ventilation in an infant with pulmonary alveolar proteinosis. Pediatr Pulmonol 1998, 26:283-286.
• [17]Dargaville PA, Mills JF, Headley BM, Chan Y, Coleman L, Loughnan PM, et al.: Therapeutic lung lavage in the piglet model of meconium aspiration syndrome. Am J Respir Crit Care Med 2003, 168:456-463.
• [18]Fiedler W, Weh HJ, Hegewisch-Becker S, Hossfeld DK: GCSF gene is expressed but not rearranged in a patient with isochromosome 17q positive acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1993, 68:49-51.
• [19]Latzin P, Tredano M, Wüst Y, de Blic J, Nicolai T, Bewig B, et al.: Anti-GM-CSF antibodies in pediatric pulmonary alveolar proteinosis. Thorax 2005, 60:39-44.
• [20]Trapnell BC, Carey BC, Uchida K, Suzuki T: Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages. Curr Opin Immunol 2009, 21:514-521.
• [21]Lindemann R, Rajka T, Henrichsen T, Vinorum OG, de Lange C, Erichsen A, et al.: Bronchioalveolar lavage with perfluorochemical liquid during conventional ventilation. Pediatr Crit Care Med 2007, 8:486-488.
• [22]Venkateshiah SB, Yan TD, Bonfield TL, Thomassen MJ, Meziane M, Czich C, et al.: An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis. Chest 2006, 130:227-237.
• [23]Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, et al.: Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2010, 181:1345-1354.
• [24]de Blic J: Pulmonary alveolar proteinosis in children. Paediatr Respir Rev 2004, 5:316-322.
• [25]Mahut B, de Blic J, Le Bourgeois M, Beringer A, Chevalier J-Y, Scheinmann : Partial and massive lung lavages in an infant with severe pulmonary alveolar proteinosis. Pediatr Pulmonol 1992, 13:50-53.