Miyashita K, Hozumi H, Inoue Y, Suzuki T, Suda T. Nationwide survey of adult patients with pulmonary alveolar proteinosis using the National Database of designated intractable diseases of Japan. Respir Investig. 2023;61:364–70. https://doi.org/10.1016/j.resinv.2023.02.011.

Article  CAS  PubMed  Google Scholar 

McCarthy C, Avetisyan R, Carey BC, Chalk C, Trapnell BC. Prevalence and healthcare burden of pulmonary alveolar proteinosis. Orphanet J Rare Dis. 2018;13:129. https://doi.org/10.1186/s13023-018-0846-y.

Article  PubMed  PubMed Central  Google Scholar 

Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med. 1958;258:1123–42. https://doi.org/10.1056/NEJM195806052582301.

Article  CAS  PubMed  Google Scholar 

Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med. 2003;349:2527–39. https://doi.org/10.1056/NEJMra023226.

Article  CAS  PubMed  Google Scholar 

• McCarthy C, Carey BC, Trapnell BC. Autoimmune Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med. 2022;205:1016–35. https://doi.org/10.1164/rccm.202112-2742SO. State of the art comprehensive review of autoimmune pulmonary alveolar proteinosis.

Article  CAS  PubMed  Google Scholar 

Inoue Y, Trapnell BC, Tazawa R, Arai T, Takada T, Hizawa N, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med. 2008;177:752–62. https://doi.org/10.1164/rccm.200708-1271OC.

Article  PubMed  PubMed Central  Google Scholar 

Han S, Mallampalli RK. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Ann Am Thorac Soc. 2015;12:765–74. https://doi.org/10.1513/AnnalsATS.201411-507FR.

Article  PubMed  PubMed Central  Google Scholar 

Gschwend J, Sherman SPM, Ridder F, Feng X, Liang H-E, Locksley RM, et al. Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth. J Exp Med. 2021. https://doi.org/10.1084/jem.20210745.

Article  PubMed  PubMed Central  Google Scholar 

Schneider C, Nobs SP, Kurrer M, Rehrauer H, Thiele C, Kopf M. Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol. 2014;15:1026–37. https://doi.org/10.1038/ni.3005.

Article  CAS  PubMed  Google Scholar 

Wojcik AJ, Skaflen MD, Srinivasan S, Hedrick CC. A critical role for ABCG1 in macrophage inflammation and lung homeostasis. J Immunol. 2008;180:4273–82. https://doi.org/10.4049/jimmunol.180.6.4273.

Article  CAS  PubMed  Google Scholar 

Wang B, Tontonoz P. Liver X receptors in lipid signalling and membrane homeostasis. Nat Rev Endocrinol. 2018;14:452–63. https://doi.org/10.1038/s41574-018-0037-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J, et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5:16. https://doi.org/10.1038/s41572-019-0066-3.

Article  PubMed  Google Scholar 

McCarthy C, Lee E, Bridges JP, Sallese A, Suzuki T, Woods JC, et al. Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis. Nat Commun. 2018;9:3127. https://doi.org/10.1038/s41467-018-05491-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sakagami T, Uchida K, Suzuki T, Carey BC, Wood RE, Wert SE, et al. Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis. N Engl J Med. 2009;361:2679–81. https://doi.org/10.1056/NEJMc0904077.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dhagat U, Hercus TR, Broughton SE, Nero TL, Cheung Tung Shing KS, Barry EF, et al. The mechanism of GM-CSF inhibition by human GM-CSF auto-antibodies suggests novel therapeutic opportunities. MAbs. 2018;10:1018–29. https://doi.org/10.1080/19420862.2018.1494107.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Uchida K. High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Blood. 2003;103:1089–98. https://doi.org/10.1182/blood-2003-05-1565.

Article  CAS  PubMed  Google Scholar 

Hwang JA, Song JH, Kim JH, Chung MP, Kim DS, Song JW, et al. Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey. BMC Pulm Med. 2017;17:147. https://doi.org/10.1186/s12890-017-0493-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Uchida K, Nakata K, Suzuki T, Luisetti M, Watanabe M, Koch DE, et al. Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. Blood. 2009;113:2547–56. https://doi.org/10.1182/blood-2009-05-155689.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seymour JF, Doyle IR, Nakata K, Presneill JJ, Schoch OD, Hamano E, 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;58:252–7. https://doi.org/10.1136/thorax.58.3.252.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ataya A, Knight V, Carey BC, Lee E, Tarling EJ, Wang T. The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review. Front Immunol. 2021;12: 752856. https://doi.org/10.3389/fimmu.2021.752856.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mabo A, Borie R, Wemeau-Stervinou L, Uzunhan Y, Gomez E, Prevot G, et al. Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort. Thorax. 2023;79:68–74. https://doi.org/10.1136/thorax-2023-220040.

Article  PubMed  Google Scholar 

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;21:514–21. https://doi.org/10.1016/j.coi.2009.09.004.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trapnell BC, Whitsett JA. GM-CSF Regulates Pulmonary Surfactant Homeostasis and Alveolar Macrophage-Mediated Innate Host Defense. Annu Rev Physiol. 2002;64:775–802. https://doi.org/10.1146/annurev.physiol.64.090601.113847.

Article  CAS  PubMed  Google Scholar 

Campo I, Mariani F, Rodi G, Paracchini E, Tsana E, Piloni D, et al. Assessment and management of pulmonary alveolar proteinosis in a reference center. Orphanet J Rare Dis. 2013;8:40. https://doi.org/10.1186/1750-1172-8-40.

Article  PubMed  PubMed Central  Google Scholar 

Hawkins P, Chawke L, Cormican L, Wikenheiser-Brokamp KA, Fabre A, Keane MP, et al. Autoimmune pulmonary alveolar proteinosis: a discrepancy between symptoms and CT findings. Lancet. 2021;398: e7. https://doi.org/10.1016/S0140-6736(21)01254-X.

Article  PubMed  Google Scholar 

Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. 2002;166:215–35. https://doi.org/10.1164/rccm.2109105.

Article  PubMed  Google Scholar 

Punatar AD, Kusne S, Blair JE, Seville MT, Vikram HR. Opportunistic infections in patients with pulmonary alveolar proteinosis. J Infect. 2012;65:173–9. https://doi.org/10.1016/j.jinf.2012.03.020.

Article  PubMed  Google Scholar 

Mariani F, Infusino C, Lettieri S, Piloni D, Bosio M, De Silvestri A, et al. Lung fibrosis in Pulmonary Alveolar Proteinosis (PAP): different stages of a syndrome or distinct diseases? Rare ILD / DPLD. European Respiratory Society. 2021. https://doi.org/10.1183/13993003.congress-2021.PA2369.

Article  Google Scholar 

Hunt AN, Malur A, Monfort T, Lagoudakis P, Mahajan S, Postle AD, et al. Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis. Am J Respir Cell Mol Biol. 2017;57:448–58. https://doi.org/10.1165/rcmb.2016-0242OC.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seymour JF. Extra-pulmonary aspects of acquired pulmonary alveolar proteinosis as predicted by granulocyte-macrophage colony-stimulating factor-deficient mice. Respirology. 2006. https://doi.org/10.1111/j.1440-1843.2006.00801.x.

Article  PubMed  Google Scholar 

Da Nam B, Kim TJ, Chung MP, Chung MJ, Kim TS, Lee KS. CT findings in pulmonary alveolar proteinosis: serial changes and prognostic implications. J Thorac Dis. 2018;10:5774–83. https://doi.org/10.21037/jtd.2018.09.86.

Article  PubMed  PubMed Central  Google Scholar 

Fijołek J, Wiatr E, Radzikowska E, Bestry I, Langfort R, Polubiec-Kownacka M, et al. Pulmonary alveolar proteinosis during a 30-year observation. Diagnosis and treatment Pneumonol Alergol Pol. 2014;82:206–17. https://doi.org/10.5603/PiAP.2014.0028.

Article  PubMed  Google Scholar 

Uchida K, Nakata K, Carey B, Chalk C, Suzuki T, Sakagami T, et al. Standardized serum GM-CSF autoantibody te