Treatments in Respiratory Medicine

, Volume 3, Issue 4, pp 217–227

Pulmonary Alveolar Proteinosis

Clinical Manifestations and Optimal Treatment Strategies
  • Saiprakash B. Venkateshiah
  • Mary Jane Thomassen
  • Mani S. Kavuru
Therapy In Practice


Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant phospholipids and proteins within the lung alveoli. Important advances have been made over the past 8 years in our understanding of this disease, offering new directions for research and patient care. First, genetically altered mice that are homozygous for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene developed a lung lesion with histologic resemblance to PAP. The surfactant is thought to be catabolized or cleared mostly by alveolar macrophages, this process being dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found in serum and bronchoalveolar lavage fluid of patients with idiopathic PAP but not in healthy controls, thereby raising the suspicion that human PAP may be an autoimmune disease. The relationship between the antibody and disease pathogenesis remains unclear but data suggest that the GM-CSF antibody may have a potential role as a diagnostic test.

No specific therapy exists for PAP. Sequential whole lung lavage is the standard of care. Exogenous therapy with GM-CSF may improve the lung disease in some patients with PAP but this therapy is still experimental. Interventions directed at treating a relative GM-CSF deficiency by administration of GM-CSF or lowering the antibody level (i.e. by plasmapheresis or immunosuppression) may hold promise as future therapy for this rare disease.


  1. 1.
    Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med 1958; 258: 1123–42PubMedCrossRefGoogle Scholar
  2. 2.
    Goldstein LS, Kavuru MS, Curtis-McCarthy P, et al. Pulmonary alveolar proteinosis: clinical features and outcomes. Chest 1998; 114: 1357–62PubMedCrossRefGoogle Scholar
  3. 3.
    Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002; 166: 215–35PubMedCrossRefGoogle Scholar
  4. 4.
    Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 1994; 264: 713–6PubMedCrossRefGoogle Scholar
  5. 5.
    Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci U S A 1994; 91: 5592–6PubMedCrossRefGoogle Scholar
  6. 6.
    Kitamura T, Tanaka N, Watanabe J, et al. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med 1999; 190: 875–80PubMedCrossRefGoogle Scholar
  7. 7.
    Thomassen MJ, Yi T, Raychaudhuri B, et al. Pulmonary alveolar proteinosis is a disease of decreased availability of GM-CSF rather than an intrinsic cellular defect. Clin Immunol 2000; 95: 85–92PubMedCrossRefGoogle Scholar
  8. 8.
    Hoffman RM, Rogers RM. Pulmonary alveolar proteinosis. In: Bone RC, Dantzker DR, editors. Pulmonary and critical care medicine. Vol. 2. SLouis (MO): Mosby Year Book, 1993: 1–7Google Scholar
  9. 9.
    Ben-Dov I, Kishinevski Y, Roznman J, et al. Pulmonary alveolar proteinosis in Israel: ethnic clustering. Isr Med Assoc J 1999; 1: 75–8PubMedGoogle Scholar
  10. 10.
    Asamoto H, Kitaichi M, Nishimura K, et al. Primary pulmonary alveolar proteinosis: clinical observation of 68 patients in Japan [in Japanese]. Nihon Kyobu Shikkan Gakkai Zasshi 1995; 33: 835–45PubMedGoogle Scholar
  11. 11.
    Prakash UB, Barham SS, Carpenter HA, et al. Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 1987; 62: 499–518PubMedCrossRefGoogle Scholar
  12. 12.
    Anton HC, Gray B. Pulmonary alveolar proteinosis presenting with pneumothorax. Clin Radiol 1967; 18: 428–31PubMedCrossRefGoogle Scholar
  13. 13.
    Oliva PB, Vogel JH. Reactive pulmonary hypertension in alveolar proteinosis. Chest 1970; 58: 167–8PubMedCrossRefGoogle Scholar
  14. 14.
    Ramirez J. Pulmonary alveolar proteinosis: treatment by massive bronchopulmonary lavage. Arch Intern Med 1967; 119: 147–56PubMedCrossRefGoogle Scholar
  15. 15.
    Mazzone PJ, Thomassen MJ, Kavuru MS. Pulmonary alveolar proteinosis: recent advances. Semin Respir Crit Care Med 2002; 23: 115–26PubMedCrossRefGoogle Scholar
  16. 16.
    Godwin JD, Muller NL, Takasugi JE. Pulmonary alveolar proteinosis: CT findings. Radiology 1988; 169: 609–13PubMedGoogle Scholar
  17. 17.
    Rubinstein I, Mullen JB, Hoffstein V. Morphologic diagnosis of idiopathic pulmonary alveolar lipoproteinosis: revisited. Arch Intern Med 1988; 148: 813–6PubMedCrossRefGoogle Scholar
  18. 18.
    Lee KN, Levin DL, Webb WR, et al. Pulmonary alveolar proteinosis: high-resolution CT, chest radiographic, and functional correlations. Chest 1997; 111: 989–95PubMedCrossRefGoogle Scholar
  19. 19.
    Holbert JM, Costello P, Li W, et al. CT features of pulmonary alveolar proteinosis. AJR Am J Roentgenol 2001; 176: 1287–94PubMedGoogle Scholar
  20. 20.
    Johkoh T, Itoh H, Muller NL, et al. Crazy-paving appearance at thin-section CT: spectrum of disease and pathologic findings. Radiology 1999; 211: 155–60PubMedGoogle Scholar
  21. 21.
    Murayama S, Murakami J, Yabuuchi H, et al. “Crazy paving appearance” on high resolution CT in various diseases. J Comput Assist Tomogr 1999; 23: 749–52PubMedCrossRefGoogle Scholar
  22. 22.
    Shah PL, Hanseil D, Lawson PR, et al. Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax 2000; 55: 67–77PubMedCrossRefGoogle Scholar
  23. 23.
    Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know. Cleve Clin J Med 2001; 68: 977–8, 981–2, 984–5 passimPubMedCrossRefGoogle Scholar
  24. 24.
    Martin RJ, Rogers RM, Myers NM. Pulmonary alveolar proteinosis: shunt fraction and lactic acid dehydrogenase concentration as aids to diagnosis. Am Rev Respir Dis 1978; 117: 1059–62PubMedGoogle Scholar
  25. 25.
    Hoffman RM, Rogers RM. Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis. Am Rev Respir Dis 1991; 143: 42–6PubMedGoogle Scholar
  26. 26.
    Takahashi T, Munakata M, Suzuki I, et al. Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar proteinosis. Am J Respir Crit Care Med 1998; 158: 1294–8PubMedGoogle Scholar
  27. 27.
    Honda Y, Kuroki Y, Matsuura E, et al. Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med 1995; 152: 1860–6PubMedGoogle Scholar
  28. 28.
    Kuroki Y, Tsutahara S, Shijubo N, et al. Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. Am Rev Respir Dis 1993; 147: 723–9PubMedGoogle Scholar
  29. 29.
    Wang BM, Stern EJ, Schmidt RA, et al. Diagnosing pulmonary alveolar proteinosis: a review and an update. Chest 1997; 111: 460–6PubMedCrossRefGoogle Scholar
  30. 30.
    Maygarden SJ, Iacocca MV, Funkhouser WK, et al. Pulmonary alveolar proteinosis: a spectrum of cytologie, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid. Diagn Cytopathol 2001; 24: 389–95PubMedCrossRefGoogle Scholar
  31. 31.
    Chou CW, Lin FC, Tung SM, et al. Diagnosis of pulmonary alveolar proteinosis: usefulness of papanicolaou-stained smears of bronchoalveolar lavage fluid. Arch Intern Med 2001; 161: 562–6PubMedCrossRefGoogle Scholar
  32. 32.
    Costello JF, Moriarty DC, Branthwaite MA, et al. Diagnosis and management of alveolar proteinosis: the role of electron microscopy. Thorax 1975; 30: 121–32PubMedCrossRefGoogle Scholar
  33. 33.
    Gilmore LB, Talley FA, Hook GE. Classification and morphometric quantitation of insoluble materials from the lungs of patients with alveolar proteinosis. Am J Pathol1988; 133: 252–64PubMedGoogle Scholar
  34. 34.
    Divertie MB, Brown AL, Harrison EG. Pulmonary alveolar proteinosis two cases studied by electron microscopy. Am J Med 1966; 40: 351–9CrossRefGoogle Scholar
  35. 35.
    Miller PA, Ravin CE, Smith GJ, et al. Pulmonary alveolar proteinosis with interstitial involvement. AJR Am J Roentgenol 1981; 137: 1069–71PubMedGoogle Scholar
  36. 36.
    Clague HW, Wallace AC, Morgan WK. Pulmonary interstitial fibrosis associated with alveolar proteinosis. Thorax 1983; 38: 865–6PubMedCrossRefGoogle Scholar
  37. 37.
    Hudson AR, Halprin GM, Miller JA, et al. Pulmonary interstitial fibrosis following alveolar proteinosis. Chest 1974; 65: 700–2PubMedCrossRefGoogle Scholar
  38. 38.
    Kaplan AI, Sabin S. Case report: interstitial fibrosis after uncomplicated pulmonary alveolar proteinosis. Postgrad Med 1977; 61: 263, 265PubMedGoogle Scholar
  39. 39.
    Wasserman K, Mason GR. Pulmonary alveolar proteinosis. In: Mumrray JF, Nadel JA, editors. Textbook of respiratory medicine. Vol. 2. Piladelphia: Saunders, 1994: 1933–46Google Scholar
  40. 40.
    Mikami T, Yamamoto Y, Yokoyama M, et al. Pulmonary alveolar proteinosis: diagnosis using routinely processed smears of bronchoalveolar lavage fluid. J Clin Pathol 1997; 50: 981–4PubMedCrossRefGoogle Scholar
  41. 41.
    Buechner HA, Ansari A. Acute silico-proteinosis: a new pathologic variant of acute silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 1969; 55: 274–8PubMedCrossRefGoogle Scholar
  42. 42.
    Xipell JM, Ham KN, Price CG, et al. Acute silicoproteinosis. Thorax 1977; 32: 104–11PubMedCrossRefGoogle Scholar
  43. 43.
    Ziskind M, Jones RN, Weill H. Silicosis. Am Rev Respir Dis 1976; 113: 643–65PubMedGoogle Scholar
  44. 44.
    Miller RR, Churg AM, Hutcheon M, et al. Pulmonary alveolar proteinosis and aluminum dust exposure. Am Rev Respir Dis 1984; 130: 312–5PubMedGoogle Scholar
  45. 45.
    McDonald JW, Alvarez F, Keller CA. Pulmonary alveolar proteinosis in association with household exposure to fibrous insulation material. Chest 2000; 117: 1813–7PubMedCrossRefGoogle Scholar
  46. 46.
    McCunney RJ, Godefroi R. Pulmonary alveolar proteinosis and cement dust: a case report. J Occup Med 1989; 31: 233–7PubMedCrossRefGoogle Scholar
  47. 47.
    Keller CA, Frost A, Cagle PT, et al. Pulmonary alveolar proteinosis in a painter with elevated pulmonary concentrations of titanium. Chest 1995; 108: 277–80PubMedCrossRefGoogle Scholar
  48. 48.
    Dawkins SA, Gerhard H, Nevin M. Pulmonary alveolar proteinosis: a possible sequel of NO2 exposure. J Occup Med 1991; 33: 638–41PubMedGoogle Scholar
  49. 49.
    Winston DJ, Territo MC, Ho WG, et al. Alveolar macrophage dysfunction in human bone marrow transplant recipients. Am J Med 1982; 73: 859–66PubMedCrossRefGoogle Scholar
  50. 50.
    Springmeyer SC, Altman LC, Kopecky KJ, et al. Alveolar macrophage kinetics and function after interruption of canine marrow function. Am Rev Respir Dis 1982; 125: 347–51PubMedGoogle Scholar
  51. 51.
    Dirksen U, Hattenhorst U, Schneider P, et al. Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. Blood 1998; 92: 1097–103PubMedGoogle Scholar
  52. 52.
    Carnovale R, Zornoza J, Goldman AM, et al. Pulmonary alveolar proteinosis: its association with hematologic malignancy and lymphoma. Radiology 1977; 122: 303–6PubMedGoogle Scholar
  53. 53.
    Aymard JP, Gyger M, Lavallee R, et al. A case of pulmonary alveolar proteinosis complicating chronic myelogenous leukemia: a peculiar pathologic aspect of busulfan lung? Cancer 1984; 53: 954–6PubMedCrossRefGoogle Scholar
  54. 54.
    Cordonnier C, Fleury-Feith J, Escudier E, et al. Secondary alveolar proteinosis is a reversible cause of respiratory failure in leukemic patients. Am J Respir Crit Care Med 1994; 149: 788–94PubMedGoogle Scholar
  55. 55.
    Gacouin A, Le Tulzo Y, Suprin E, et al. Acute respiratory failure caused by secondary alveolar proteinosis in a patient with acute myeloid leukemia: a case report. Intensive Care Med 1998; 24: 265–7PubMedCrossRefGoogle Scholar
  56. 56.
    Haworth JC, Hoogstraten J, Taylor H. Thymic alymphoplasia. Arch Dis Child 1967; 42: 40–54PubMedCrossRefGoogle Scholar
  57. 57.
    Webster Jr JR, Battifora H, Furey C, et al. Pulmonary alveolar proteinosis in two siblings with decreased immunoglobulin A. Am J Med 1980; 69: 786–9PubMedCrossRefGoogle Scholar
  58. 58.
    Yousem SA. Alveolar lipoproteinosis in lung allograft recipients. Hum Pathol 1997; 28: 1383–6PubMedCrossRefGoogle Scholar
  59. 59.
    Israel RH, Magnussen CR. Are AIDS patients at risk for pulmonary alveolar proteinosis? Chest 1989; 96: 641–2PubMedCrossRefGoogle Scholar
  60. 60.
    Ruben FL, Talamo TS. Secondary pulmonary alveolar proteinosis occurring in two patients with acquired immune deficiency syndrome. Am J Med 1986; 80: 1187–90PubMedCrossRefGoogle Scholar
  61. 61.
    Couderc LJ, Bernaudin JF, Epardeau B, et al. Pulmonary alveolar proteinosis and disseminated Mycobacterium avium infection. Respir Med 1996; 90: 641–2PubMedCrossRefGoogle Scholar
  62. 62.
    Bakhos R, Gattuso P, Arcot C, et al. Pulmonary alveolar proteinosis: an unusual association with Mycobacterium avium-intracellulare infection and lymphocytic interstitial pneumonia. South Med J 1996; 89: 801–2PubMedCrossRefGoogle Scholar
  63. 63.
    Reyes JM, Putong PB. Association of pulmonary alveolar lipoproteinosis with mycobacterial infection. Am J Clin Pathol 1980; 74: 478–85PubMedGoogle Scholar
  64. 64.
    Witty LA, Tapson VF, Piantadosi CA. Isolation of mycobacteria in patients with pulmonary alveolar proteinosis. Medicine (Baltimore) 1994; 73: 103–9Google Scholar
  65. 65.
    Pascual J, Gomez Aguinaga MA, et al. Alveolar proteinosis and nocardiosis: a patient treated by bronchopulmonary lavage. Postgrad Med J 1989; 65: 674–7PubMedCrossRefGoogle Scholar
  66. 66.
    Tran Van Nhieu J, Vojtek AM, Bernaudin JF, et al. Pulmonary alveolar proteinosis associated with Pneumocystis carinii: ultrastructural identification in bronchoalveolar lavage in AIDS and immunocompromised non-AIDS patients. Chest 1990; 98: 801–5PubMedCrossRefGoogle Scholar
  67. 67.
    Gumpert BC, Nowacki MR, Amundson DE. Pulmonary alveolar lipoproteinosis: remission after antibiotic treatment. West J Med 1994; 161: 66–8PubMedGoogle Scholar
  68. 68.
    Teja K, Cooper PH, Squires JE, et al. Pulmonary alveolar proteinosis in four siblings. N Engl J Med 1981; 305: 1390–2PubMedCrossRefGoogle Scholar
  69. 69.
    Nogee LM, de Mello DE, Dehner LP, et al. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 1993; 328: 406–10PubMedCrossRefGoogle Scholar
  70. 70.
    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; 93: 1860–3PubMedCrossRefGoogle Scholar
  71. 71.
    Beers MF, Hamvas A, Moxley MA, et al. Pulmonary surfactant metabolism in infants lacking surfactant protein B. Am J Respir Cell Mol Biol 2000; 22: 380–91PubMedGoogle Scholar
  72. 72.
    Reed JA, Whitsett JA. Granulocyte-macrophage colony-stimulating factor and pulmonary surfactant homeostasis. Proc Assoc Am Physicians 1998; 110: 321–32PubMedGoogle Scholar
  73. 73.
    Ikegami M, Ueda T, Hull W, et al. Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation. Am J Physiol 1996; 270: L650–8PubMedGoogle Scholar
  74. 74.
    Huffman JA, Hull WM, Dranoff G, et al. Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice. J Clin Invest 1996; 97: 649–55PubMedCrossRefGoogle Scholar
  75. 75.
    Reed JA, Ikegami M, Cianciolo ER, et al. Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient mice. Am J Physiol 1999; 276: L556–63PubMedGoogle Scholar
  76. 76.
    Nishinakamura R, Wiler R, Dirksen U, et al. The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation. J Exp Med 1996; 183: 2657–62PubMedCrossRefGoogle Scholar
  77. 77.
    Cooke KR, Nishinakamura R, Martin TR, et al. Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 beta c receptor-deficient mice despite correction of alveolar proteinosis after BMT. Bone Marrow Transplant 1997; 20: 657–62PubMedCrossRefGoogle Scholar
  78. 78.
    Tanaka N, Watanabe J, Kitamura T, et al. Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor. FEBS Lett 1999; 442: 246–50PubMedCrossRefGoogle Scholar
  79. 79.
    Bonfield TL, Russell D, Burgess S, et al. Autoantibodies against granulocyte macrophage colony-stimulating factor are diagnostic for pulmonary alveolar proteinosis. Am J Respir Cell Mol Biol 2002; 27: 481–6PubMedGoogle Scholar
  80. 80.
    Parker LA, Novotny DB. Recurrent alveolar proteinosis following double lung transplantation. Chest 1997; 111: 1457–8PubMedCrossRefGoogle Scholar
  81. 81.
    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; 161: 1143–8PubMedGoogle Scholar
  82. 82.
    Seymour JF, Begley CG, Dirksen U, et al. Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis. Blood 1998; 92: 2657–67PubMedGoogle Scholar
  83. 83.
    Dirksen U, Nishinakamura R, Groneck P, et al. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. J Clin Invest 1997; 100: 2211–7PubMedCrossRefGoogle Scholar
  84. 84.
    Ikegami M, Whitsett JA, Chroneos ZC, et al. IL-4 increases surfactant and regulates metabolism in vivo. Am J Physiol Lung Cell Mol Physiol 2000; 278: L75–80PubMedGoogle Scholar
  85. 85.
    Tchou-Wong KM, Harkin TJ, Chi C, et al. GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis. Am J Respir Crit Care Med 1997; 156: 1999–2002PubMedGoogle Scholar
  86. 86.
    Ramirez J, Campbell GD. Pulmonary alveolar proteinosis: endobronchial treatment. Ann Intern Med 1965; 63: 429–41PubMedGoogle Scholar
  87. 87.
    Ramirez J, Kieffer Jr RF, Ball Jr WC. Bronchopulmonary lavage in man. Ann Intern Med 1965; 63: 819–28PubMedGoogle Scholar
  88. 88.
    Wasserman K, Blank N, Fletcher G. Lung lavage (alveolar washing) in alveolar proteinosis. Am J Med 1968; 44: 611–7PubMedCrossRefGoogle Scholar
  89. 89.
    Kao D, Wasserman K, Costley D, et al. Advances in the treatment of pulmonary alveolar proteinosis. Am Rev Respir Dis 1975; 111: 361–3PubMedGoogle Scholar
  90. 90.
    Sunderland WA, Klein RL. Heparin absorption during heparin-saline lung lavage in a patient with pulmonary alveolar proteinosis. Chest 1973; 63: 1033–4PubMedCrossRefGoogle Scholar
  91. 91.
    Hammon WE, McCaffree DR, Cucchiara AJ. A comparison of manual to mechanical chest percussion for clearance of alveolar material in patients with pulmonary alveolar proteinosis (phospholipidosis). Chest 1993; 103: 1409–12PubMedCrossRefGoogle Scholar
  92. 92.
    Avecillas J, Saad CP, Ghamande S. Comparison between unilateral and bilateral sequential whole lung lavage in pulmonary alveolar proteinosis [abstract]. Am J Respir Crit Care Med 2002; 165: A653Google Scholar
  93. 93.
    Rogers RM, Levin DC, Gray BA, et al. Physiologic effects of bronchopulmonary lavage in alveolar proteinosis. Am Rev Respir Dis 1978; 118: 255–64PubMedGoogle Scholar
  94. 94.
    Gale ME, Karlinsky JB, Robins AG. Bronchopulmonary lavage in pulmonary alveolar proteinosis: chest radiograph observations. AJR Am J Roentgenol 1986; 146: 981–5PubMedGoogle Scholar
  95. 95.
    Hoffman RM, Dauber JH, Rogers RM. Improvement in alveolar macrophage migration after therapeutic whole lung lavage in pulmonary alveolar proteinosis. Am Rev Respir Dis 1989; 139: 1030–2PubMedGoogle Scholar
  96. 96.
    Murayama J, Fukuda K, Sato T, et al. Pulmonary alveolar proteinosis. Xe-133 scintigraphic findings before and after bronchopulmonary lavage. Clin Nucl Med 1993; 18: 123–5PubMedCrossRefGoogle Scholar
  97. 97.
    Selecky PA, Wasserman K, Benfield JR, et al. The clinical and physiological effect of whole-lung lavage in pulmonary alveolar proteinosis: a ten-year experience. Ann Thorac Surg 1977; 24: 451–61PubMedCrossRefGoogle Scholar
  98. 98.
    Kavuru MP, Popovich M. Therapeutic whole lung lavage: a stop-gap therapy for alveolar proteinosis. Chest 2002; 122(4): 1123–4PubMedCrossRefGoogle Scholar
  99. 99.
    Ben-Abraham R, Greenfeld A, Rozenman J, et al. Pulmonary alveolar proteinosis: step-by-step perioperative care of whole lung lavage procedure. Heart Lung 2002; 31: 43–9PubMedCrossRefGoogle Scholar
  100. 100.
    Rogers RM, Szidon JP, Shelburne J, et al. Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. N Engl J Med 1972; 286: 1230–3PubMedCrossRefGoogle Scholar
  101. 101.
    Smith JD, Millen JE, Safar P, et al. Intrathoracic pressure, pulmonary vascular pressures and gas exchange during pulmonary lavage. Anesthesiology 1970; 33: 401–5PubMedCrossRefGoogle Scholar
  102. 102.
    Aguinaga MA, Santos P, Renes E, et al. Hemodynamic changes during whole bronchoalveolar lavage in two cases of pulmonary alveolar proteinosis. Intensive Care Med 1991; 17: 421–3PubMedCrossRefGoogle Scholar
  103. 103.
    Brach BB, Harreil JH, Moser KM. Alveolar proteinosis: lobar lavage by fiberoptic bronchoscopic technique. Chest 1976; 69: 224–7PubMedCrossRefGoogle Scholar
  104. 104.
    Heymach III GJ, Shaw RC, McDonald JA, et al. Fiberoptic bronchopulmonary lavage for alveolar proteinosis in a patient with only one lung. Chest 1982; 81: 508–10PubMedCrossRefGoogle Scholar
  105. 105.
    Nagasaka Y, Takahashi M, Ueshima H, et al. Bronchoalveolar lavage with trypsin in pulmonary alveolar proteinosis. Thorax 1996; 51: 769–70PubMedCrossRefGoogle Scholar
  106. 106.
    Cheng SL, Chang HT, Lau HP, et al. Pulmonary alveolar proteinosis: treatment by bronchofiberscopic lobar lavage. Chest 2002; 122: 1480–5PubMedCrossRefGoogle Scholar
  107. 107.
    Seymour JF, Dunn AR, Vincent JM, et al. Efficacy of granulocyte-macrophage colony-stimulating factor in acquired alveolar proteinosis. N Engl J Med 1996; 335: 1924–5PubMedCrossRefGoogle Scholar
  108. 108.
    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; 163: 524–31PubMedGoogle Scholar
  109. 109.
    Mazzone PJ, Sullivan EJ, Piccin R. Granulocyte macrophage-colony stimulating factor therapy for pulmonary alveolar proteinosis [abstract]. Am J Respir Crit Care Med 2000; 161: A888Google Scholar
  110. 110.
    Bonfield TL, Kavuru MS, Thomassen MJ. Anti-GM-CSF titer predicts response to GM-CSF therapy in pulmonary alveolar proteinosis. Clin Immunol 2002; 105: 342–50PubMedCrossRefGoogle Scholar
  111. 111.
    Barraclough RM, Gillies AJ. Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. Thorax 2001; 56: 664–5PubMedCrossRefGoogle Scholar
  112. 112.
    deVega MG, Sanchez-Palencia A, Ramirez A, et al. GM-CSF therapy in pulmonary alveolar proteinosis [letter]. Thorax 2002; 57: 837PubMedCrossRefGoogle Scholar
  113. 113.
    Schoch OD, Nierhobb N, Dubach HU, et al. Treatment of pulmonary alveolar proteinosis (PAP): is GM-CSF an option [abstract]? Eur Respir J 1998; 12: 131sGoogle Scholar
  114. 114.
    Schoch OD, Schanz U, Koller M, et al. BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF. Thorax 2002; 57: 277–80PubMedCrossRefGoogle Scholar
  115. 115.
    Seymour JF, Doyle IR, Nakata K, et al. Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis. Thorax 2003; 58: 252–7PubMedCrossRefGoogle Scholar
  116. 116.
    Lieschke GJ, Cebon J, Morstyn G. Characterization of the clinical effects after the first dose of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1989; 74: 2634–43PubMedGoogle Scholar
  117. 117.
    Anderson PM, Markovic SN, Sloan JA, et al. Aerosol granulocyte macrophagecolony stimulating factor: a low toxicity, lung-specific biological therapy in patients with lung metastases. Clin Cancer Res 1999; 5: 2316–23PubMedGoogle Scholar
  118. 118.
    Wylam ME, Ten RM, Katzmann JA. Aerosolized GM-CSF improves pulmonary function in idiopathic pulmonary alveolar proteinosis [abstract]. Am J Resp Crit Care Med 2000; 161: A889Google Scholar
  119. 119.
    Tazawa R, Ishimoto O, Suzuki T, et al. Granulocyte-macrophage colony stimulating factor inhalation therapy as a treatment for pulmonary alveolar proteinosis [abstract]. Eur Respir J 2003; 22: 377s–8sGoogle Scholar
  120. 120.
    Kavuru MS, Bonfield TL, Thomassen MJ. Plasmapheresis, GM-CSF, and alveolar proteinosis [letter]. Am J Respir Crit Care Med 2003; 167: 1036PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Saiprakash B. Venkateshiah
    • 1
  • Mary Jane Thomassen
    • 1
  • Mani S. Kavuru
    • 1
  1. 1.Department of Pulmonary and Critical Care MedicineCleveland Clinic FoundationClevelandUSA
  2. 2.Pulmonary Function LaboratoryCleveland Clinic FoundationClevelandUSA

Personalised recommendations