{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:56:23Z","timestamp":1784332583776,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pulmonary alveolar proteinosis (PAP) is a rare syndrome first described by Rosen et al. in 1958. Despite our considerably evolved understanding of PAP over the past decades, no bibliometric studies have been reported on this field. We aimed to analyze and visualize the research hotspots and current trends of the PAP research field using a bibliometric analysis to help understand the future development of basic and clinical research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The literature regarding PAP was culled from the Web of Science Core Collection (WoSCC) database. Data were extracted from the relevant articles and visually analyzed using CiteSpace and VOSviewer software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine hundred and nine qualifying articles were included in the analysis. Publications regarding PAP increased over time. These articles mainly come from 407 institutions of 57 countries. The leading countries were the USA and Japan. University of Cincinnati (USA) and Niigata University (Japan) featured the highest number of publications among all institutions. Bruce C Trapnell exerts a significant publication impact and has made the most outstanding contributions in the field of PAP. <jats:italic>American Journal of Physiology-Lung Cellular and Molecular Physiology<\/jats:italic> was the journal with the most publications, and <jats:italic>American Journal of Respiratory and Critical Care Medicine<\/jats:italic> was the most commonly cited journal. All the top 5 co-cited journals belong to Q1. Keyword citation bursts revealed that inflammation, deficiency, tissue resident macrophage, classification, autoimmune pulmonary alveolar proteinosis, sarcoidosis, gm csf, high resolution ct, and fetal monocyte were the emerging research hotspots.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Research on PAP is prosperous. International cooperation is also expected to deepen and strengthen in the future. Our results indicated that the etiology and pathogenesis of PAP, current and emerging therapies, especially the novel pathogenesis-based options will remain research hotspots in the future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.846480","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:19:50Z","timestamp":1648415990000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Bibliometric Analysis of Pulmonary Alveolar Proteinosis From 2001 to 2021"],"prefix":"10.3389","volume":"9","author":[{"given":"Shixu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangning","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjie","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1056\/NEJM195806052582301","article-title":"Pulmonary alveolar proteinosis","volume":"258","author":"Rosen","year":"1958","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-018-0846-y","article-title":"Prevalence and healthcare burden of pulmonary alveolar proteinosis","volume":"13","author":"McCarthy","year":"2018","journal-title":"Orphanet J Rare Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41572-019-0066-3","article-title":"Pulmonary alveolar proteinosis","volume":"5","author":"Trapnell","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B4","doi-asserted-by":"publisher","first-page":"701","DOI":"10.2147\/TCRM.S193884","article-title":"Update on diagnosis and treatment of adult pulmonary alveolar proteinosis","volume":"17","author":"Iftikhar","year":"2021","journal-title":"Ther Clin Risk Manag."},{"key":"B5","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/S2213-2600(18)30043-2","article-title":"Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach","volume":"6","author":"Kumar","year":"2018","journal-title":"Lancet Respir Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S1074-7613(01)00218-7","article-title":"GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU. 1","volume":"15","author":"Shibata","year":"2001","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.ijmedinf.2016.11.006","article-title":"Visualizing the knowledge structure and evolution of big data research in healthcare informatics","volume":"98","author":"Gu","year":"2017","journal-title":"Int J Med Informatics."},{"key":"B8","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/asi.20317","article-title":"CiteSpace II: detecting and visualizing emerging trends and transient patterns in scientific literature","volume":"57","author":"Chen","year":"2006","journal-title":"J Am Soc Information Sci Technol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s11192-009-0146-3","article-title":"Software survey: VOSviewer, a computer program for bibliometric mapping","volume":"84","author":"Van Eck","year":"2010","journal-title":"Scientometrics."},{"key":"B10","doi-asserted-by":"publisher","first-page":"731933","DOI":"10.3389\/fimmu.2021.731933","article-title":"A bibliometric analysis of pyroptosis from 2001 to 2021","volume":"12","author":"Ma","year":"2021","journal-title":"Front Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3163\/1536-5050.103.4.013","article-title":"Bibliometrics basics","volume":"103","author":"Cooper","year":"2015","journal-title":"J Med Libr Assoc."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5303","DOI":"10.1073\/pnas.0307513100","article-title":"Searching for intellectual turning points: progressive knowledge domain visualization","volume":"101","author":"Chen","year":"2004","journal-title":"Proc Natl Acad Sci USA."},{"key":"B13","article-title":"CiteSpace II: visualization and knowledge discovery in bibliographic databases","volume-title":"AMIA Annual Symposium Proceedings","author":"Synnestvedt","year":"2005"},{"key":"B14","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1517\/14712598.2012.674507","article-title":"Emerging trends in regenerative medicine: a scientometric analysis in CiteSpace","volume":"12","author":"Chen","year":"2012","journal-title":"Expert Opinion Biol Ther."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1056\/NEJMra023226","article-title":"Pulmonary alveolar proteinosis","volume":"349","author":"Trapnell","year":"2003","journal-title":"N Engl J Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1164\/rccm.2109105","article-title":"Pulmonary alveolar proteinosis: progress in the first 44 years","volume":"166","author":"Seymour","year":"2002","journal-title":"Am J Respir Crit Care Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1084\/jem.190.6.875","article-title":"Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte\/macrophage colony-stimulating factor","volume":"190","author":"Kitamura","year":"1999","journal-title":"J Exp Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1126\/science.8171324","article-title":"Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis","volume":"264","author":"Dranoff","year":"1994","journal-title":"Science."},{"key":"B19","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1164\/rccm.200708-1271OC","article-title":"Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan","volume":"177","author":"Inoue","year":"2008","journal-title":"Am J Respir Crit Care Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5592","DOI":"10.1073\/pnas.91.12.5592","article-title":"Granulocyte\/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology","volume":"91","author":"Stanley","year":"1994","journal-title":"Proc Natl Acad Sci USA."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1182\/blood-2003-05-1565","article-title":"High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis","volume":"103","author":"Uchida","year":"2004","journal-title":"Blood."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2703","DOI":"10.1084\/jem.20080990","article-title":"Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA","volume":"205","author":"Suzuki","year":"2008","journal-title":"J Exp Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1183\/09031936.00197710","article-title":"An open-label trial of rituximab therapy in pulmonary alveolar proteinosis","volume":"38","author":"Kavuru","year":"2011","journal-title":"Euro Respir J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1056\/NEJMoa1816216","article-title":"Inhaled GM-CSF for pulmonary alveolar proteinosis","volume":"381","author":"Tazawa","year":"2019","journal-title":"N Engl J Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1164\/rccm.200906-0978OC","article-title":"Inhaled granulocyte\/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis","volume":"181","author":"Tazawa","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1056\/NEJMoa062505","article-title":"GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis","volume":"356","author":"Uchida","year":"2007","journal-title":"N Engl J Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1164\/rccm.201002-0271OC","article-title":"Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy","volume":"182","author":"Suzuki","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.stemcr.2016.06.011","article-title":"Murine iPSC-derived macrophages as a tool for disease modeling of hereditary pulmonary alveolar proteinosis due to Csf2rb deficiency","volume":"7","author":"Mucci","year":"2016","journal-title":"Stem Cell Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/nature13807","article-title":"Pulmonary macrophage transplantation therapy","volume":"514","author":"Suzuki","year":"2014","journal-title":"Nature."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-05491-z","article-title":"Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis","volume":"9","author":"McCarthy","year":"2018","journal-title":"Nat Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1164\/ajrccm.162.2.9910032","article-title":"Serological diagnosis of idiopathic pulmonary alveolar proteinosis","volume":"162","author":"Kitamura","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12931-018-0780-5","article-title":"Rituximab for auto-immune alveolar proteinosis, a real life cohort study","volume":"19","author":"Soyez","year":"2018","journal-title":"Respir Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1378\/chest.130.1.227","article-title":"An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis","volume":"130","author":"Venkateshiah","year":"2006","journal-title":"Chest."},{"key":"B34","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S0014-5793(98)01668-8","article-title":"Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor","volume":"442","author":"Tanaka","year":"1999","journal-title":"FEBS Lett."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1002\/j.1460-2075.1989.tb08541.x","article-title":"Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor","volume":"8","author":"Gearing","year":"1989","journal-title":"EMBO J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/ni.3005","article-title":"Induction of the nuclear receptor PPAR-\u03b3 by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages","volume":"15","author":"Schneider","year":"2014","journal-title":"Nat Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"L1132","DOI":"10.1152\/ajplung.00216.2003","article-title":"PU. 1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage colony-stimulating factor","volume":"285","author":"Bonfield","year":"2003","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/83328","article-title":"The role of PPAR-\u03b3 in macrophage differentiation and cholesterol uptake","volume":"7","author":"Moore","year":"2001","journal-title":"Nat Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-10879-w","article-title":"Targeting cholesterol homeostasis in lung diseases","volume":"7","author":"Sallese","year":"2017","journal-title":"Sci Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/1074-7613(95)90046-2","article-title":"Mice deficient for the IL-3\/GM-CSF\/IL-5 \u03b2c receptor exhibit lung pathology and impaired immune response, while \u03b2IL3 receptor-deficient mice are normal","volume":"2","author":"Nishinakamura","year":"1995","journal-title":"Immunity."},{"key":"B41","doi-asserted-by":"publisher","first-page":"9565","DOI":"10.1073\/pnas.92.21.9565","article-title":"Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5","volume":"92","author":"Robb","year":"1995","journal-title":"Proc Natl Acad Sci USA."},{"key":"B42","first-page":"4857","article-title":"Pulmonary macrophage transplantation therapy in Csf2ra gene-ablated mice: a novel model of hereditary pulmonary alveolar proteinosis in children","volume-title":"B108 Cystic Fibrosis, Primary Ciliary Dyskinesia, and ILD","author":"Shima","year":"2017"},{"key":"B43","article-title":"Development and validation of Csf2ra gene-deficient mice as a clinically relevant model of children with hereditary pulmonary alveolar proteinosis","volume-title":"B108 Cystic Fibrosis, Primary Ciliary Dyskinesia, and ILD","author":"Suzuki","year":"2017"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1056\/NEJMc070650","article-title":"GM-CSF autoantibodies in pulmonary alveolar proteinosis","volume":"353","author":"Bendtzen","year":"2005","journal-title":"N Engl J Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1164\/rccm.201001-0008OC","article-title":"Patient-derived granulocyte\/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates","volume":"182","author":"Sakagami","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1056\/NEJMc0904077","article-title":"Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis","volume":"361","author":"Sakagami","year":"2009","journal-title":"N Engl J Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"819","DOI":"10.7326\/0003-4819-63-5-819","article-title":"Bronchopulmonary lavage in man","volume":"63","author":"Ramirez-R","year":"1965","journal-title":"Ann Internal Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1097\/LBR.0000000000000180","article-title":"Therapeutic whole-lung lavage for pulmonary alveolar proteinosis: a procedural update","volume":"22","author":"Abdelmalak","year":"2015","journal-title":"J Bronchol Interventional Pulmonol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1378\/chest.09-2295","article-title":"Whole-lung lavage for pulmonary alveolar proteinosis","volume":"136","author":"Michaud","year":"2009","journal-title":"Chest."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-016-0497-9","article-title":"Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures","volume":"11","author":"Campo","year":"2016","journal-title":"Orphanet J Rare Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1056\/NEJM199612193352513","article-title":"Efficacy of granulocyte-macrophage colony-stimulating factor in acquired alveolar proteinosis","volume":"335","author":"Seymour","year":"1996","journal-title":"N Engl J Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1164\/ajrccm.163.2.2003146","article-title":"Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis","volume":"163","author":"Seymour","year":"2001","journal-title":"Am J Respir Crit Care Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1056\/NEJMoa1913590","article-title":"Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis","volume":"383","author":"Trapnell","year":"2020","journal-title":"N Engl J Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12890-015-0085-0","article-title":"Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study","volume":"15","author":"Akasaka","year":"2015","journal-title":"BMC Pulmonary Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.rmr.2016.06.002","article-title":"Plasmapheresis failure in the treatment of auto-immune pulmonary alveolar proteinosis","volume":"34","author":"Jezequel","year":"2017","journal-title":"Revue Maladies Respir."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1183\/09031936.00097508","article-title":"Plasmapheresis for treatment of pulmonary alveolar proteinosis","volume":"33","author":"Luisetti","year":"2009","journal-title":"Euro Respir J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1038\/bmt.2010.321","article-title":"Pulmonary alveolar proteinosis following allogeneic hematopoietic cell transplantation","volume":"46","author":"Pidala","year":"2011","journal-title":"Bone Marrow Transplant."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.846480\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:19:54Z","timestamp":1648415994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.846480\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":57,"alternative-id":["10.3389\/fmed.2022.846480"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.846480","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]},"article-number":"846480"}}