{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:41:41Z","timestamp":1792215701727,"version":"4.4.0"},"reference-count":20,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["HCQ4SurfDefect"],"award-info":[{"award-number":["HCQ4SurfDefect"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Gr 970\/9-1"],"award-info":[{"award-number":["Gr 970\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2022,1,19]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare.<\/jats:p><jats:p>In this first case series on autoimmune PAP, we detail the presentation and management issues of four children.<\/jats:p><jats:p>Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach.<\/jats:p><jats:p>The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults.<\/jats:p>","DOI":"10.1183\/23120541.00701-2021","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T16:56:22Z","timestamp":1647536182000},"page":"00701-2021","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Autoimmune pulmonary alveolar proteinosis in children"],"prefix":"10.1183","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-912X","authenticated-orcid":false,"given":"Matthias","family":"Griese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Panagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Effrosyni D.","family":"Manali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-8315","authenticated-orcid":false,"given":"Mirjam","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-7749","authenticated-orcid":false,"given":"Nicolaus","family":"Schwerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7632-1159","authenticated-orcid":false,"given":"Konstantinos","family":"Douros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kallieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7360-6001","authenticated-orcid":false,"given":"Ruth Maria","family":"Urbantat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-7675","authenticated-orcid":false,"given":"Horst","family":"von Bernuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-609X","authenticated-orcid":false,"given":"Lykourgos","family":"Kolilekas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lurdes","family":"Morais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-5666","authenticated-orcid":false,"given":"Ana","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Landwehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-692X","authenticated-orcid":false,"given":"Katrin","family":"Knoflach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-6610","authenticated-orcid":false,"given":"Florian","family":"Gothe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-6655","authenticated-orcid":false,"given":"Karl","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-3002","authenticated-orcid":false,"given":"Vassiliki","family":"Papaevangelou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3592-0037","authenticated-orcid":false,"given":"Athanasios G.","family":"Kaditis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kanaka-Gantenbein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros A.","family":"Papiris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"2024101711293300000_8.1.00701-2021.1","doi-asserted-by":"crossref","first-page":"16","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":"2024101711293300000_8.1.00701-2021.2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0610"},{"key":"2024101711293300000_8.1.00701-2021.3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/s13256-021-02906-2","article-title":"Autoimmune pulmonary alveolar proteinosis successfully treated with lung lavage in an adolescent patient: a case report","volume":"15","author":"Alasiri","year":"2021","journal-title":"J Med Case Rep"},{"key":"2024101711293300000_8.1.00701-2021.4","doi-asserted-by":"crossref","first-page":"e571","DOI":"10.1097\/PEC.0000000000001820","article-title":"Pulmonary alveolar proteinosis: a case of profound hypoxemia in a previously healthy teenager","volume":"37","author":"Feld","year":"2021","journal-title":"Pediatr Emerg Care"},{"key":"2024101711293300000_8.1.00701-2021.5","first-page":"101100","article-title":"Autoimmune pulmonary alveolar proteinosis mimicking Mycoplasma pneumonia in an adolescent","volume":"30","author":"Meka","year":"2020","journal-title":"Respir Med Case Rep"},{"key":"2024101711293300000_8.1.00701-2021.6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1056\/NEJMcps0901689","article-title":"Clinical problem-solving. A crazy cause of dyspnea","volume":"364","author":"Miller","year":"2011","journal-title":"N Engl J Med"},{"key":"2024101711293300000_8.1.00701-2021.7","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1097\/PEC.0000000000001536","article-title":"Pulmonary alveolar proteinosis in hereditary and autoimmune forms with 2 cases","volume":"36","author":"Sirin Kose","year":"2020","journal-title":"Pediatr Emerg Care"},{"key":"2024101711293300000_8.1.00701-2021.8","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2012-006987"},{"key":"2024101711293300000_8.1.00701-2021.9","doi-asserted-by":"crossref","first-page":"641","DOI":"10.12659\/AJCR.897868","article-title":"Successful treatment of autoimmune pulmonary alveolar proteinosis in a pediatric patient","volume":"17","author":"Trukalj","year":"2016","journal-title":"Am J Case Rep"},{"key":"2024101711293300000_8.1.00701-2021.10","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0171-z"},{"key":"2024101711293300000_8.1.00701-2021.11","unstructured":"Webb WR , M\u00fcller NL , Naidich DP . High-resolution CT of the Lung. 4th Edn. Philadelphia, Lippincott Williams & Wilkins, 2009."},{"key":"2024101711293300000_8.1.00701-2021.12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/ppul.25070","article-title":"Pediatric lung imaging features of COVID-19: a systematic review and meta-analysis","volume":"56","author":"Nino","year":"2021","journal-title":"Pediatr Pulmonol"},{"key":"2024101711293300000_8.1.00701-2021.13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1586\/17476348.2015.1035259","article-title":"Pulmonary alveolar proteinosis: time to shift?","volume":"9","author":"Papiris","year":"2015","journal-title":"Expert Rev Respir Med"},{"key":"2024101711293300000_8.1.00701-2021.14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13244-020-00933-z","article-title":"COVID-19 pneumonia: the great radiological mimicker","volume":"11","author":"Duzgun","year":"2020","journal-title":"Insights Imaging"},{"key":"2024101711293300000_8.1.00701-2021.15","doi-asserted-by":"crossref","first-page":"115","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":"2024101711293300000_8.1.00701-2021.16","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00540-020-02812-9","article-title":"General anesthesia affecting on developing brain: evidence from animal to clinical research","volume":"34","author":"Liu","year":"2020","journal-title":"J Anesth"},{"key":"2024101711293300000_8.1.00701-2021.17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2009.01539.x"},{"key":"2024101711293300000_8.1.00701-2021.18","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s40261-014-0208-z","article-title":"Long-term inhaled granulocyte-macrophage-colony stimulating factor in autoimmune pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose","volume":"34","author":"Papiris","year":"2014","journal-title":"Clin Drug Investig"},{"key":"2024101711293300000_8.1.00701-2021.19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12931-018-0862-4","article-title":"Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses","volume":"19","author":"Sheng","year":"2018","journal-title":"Respir Res"},{"key":"2024101711293300000_8.1.00701-2021.20","doi-asserted-by":"crossref","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"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.00701-2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:14:40Z","timestamp":1740374080000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.00701-2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,3,24]]},"published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1183\/23120541.00701-2021"],"URL":"https:\/\/doi.org\/10.1183\/23120541.00701-2021","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]}}}