{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:06:25Z","timestamp":1789981585920,"version":"4.0.1"},"reference-count":50,"publisher":"European Respiratory Society (ERS)","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015511","name":"Savara Pharmaceuticals","doi-asserted-by":"publisher","award":["provided study drug"],"award-info":[{"award-number":["provided study drug"]}],"id":[{"id":"10.13039\/100015511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"Deutsches Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC2026, SFB-TRR84, KFO309, SFB1021"],"award-info":[{"award-number":["EXC2026, SFB-TRR84, KFO309, SFB1021"]}],"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":[[2026,3,22]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) enhances pulmonary host defence and promotes re-establishment of alveolar barrier function. We investigated the safety, feasibility and efficacy of nebulised recombinant human (rh)GM-CSF (molgramostim) in pneumonia-related acute respiratory distress syndrome (ARDS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicentre, randomised, double-blind, parallel-group, placebo-controlled, investigator-initiated phase 2a trial, patients were randomised to receive nebulised low-dose (150\u2005\u03bcg) or high-dose (450\u2005\u03bcg) rhGM-CSF or placebo for 3\u2005days. Bronchoalveolar lavage (BAL) was performed before the first dose and after dosing. The primary outcome parameter was the composite GI-HOPE score, representing expression changes of CD80, CD86, CD206 and human leukocyte antigen (HLA)-DR on alveolar macrophages after dosing compared to baseline. Secondary outcomes included oxygenation, Sequential Organ Failure Assessment (SOFA) scores and clinical end-points at day 28.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      46 participants were randomised, 43 completed treatment (n=15 placebo, n=16 low dose and n=12 high dose), and BAL was performed on 38 participants before and after treatment. Although the composite biological GI-HOPE score did not reach significance (p&gt;0.05), high-dose treatment caused upregulation of HLA-DR and CD206 on alveolar macrophages, indicating deposition in the alveolar compartment and beneficial macrophage activation (HLA-DR: p=0.0406\n                      <jats:italic>versus<\/jats:italic>\n                      low dose, p=0.1841\n                      <jats:italic>versus<\/jats:italic>\n                      placebo; CD206: p=0.009\n                      <jats:italic>versus<\/jats:italic>\n                      low dose, p=0.0179\n                      <jats:italic>versus<\/jats:italic>\n                      placebo). High-dose rhGM-CSF treatment revealed a favourable profile of oxygenation at the end of analysis compared to time-points before inhalation (p=0.095 and p=0.0175) or compared to the low-dose and placebo groups (p=0.0063 and p=0.0198; visit 13), and was associated with decreased SOFA scores in the high-dose group over time (p=0.0013 and p=0.00023 compared to low dose and placebo). Importantly, inhaled rhGM-CSF did not increase alveolar or systemic inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inhalation of 450\u2005\u03bcg rhGM-CSF was safe, and promoted a favourable profile regarding alveolar macrophage activation, oxygenation and SOFA scores over time; however, it did not lead to differences in the GI-HOPE score.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01795-2025","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:45:19Z","timestamp":1776959119000},"page":"01795-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhaled granulocyte\u2013macrophage colony-stimulating factor (molgramostim) as host-directed therapy for pneumonia-related acute respiratory distress syndrome: a multicentre, randomised, placebo-controlled phase 2a trial (GI-HOPE)"],"prefix":"10.1183","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-0911","authenticated-orcid":false,"given":"Susanne","family":"Herold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-7356","authenticated-orcid":false,"given":"Tobias","family":"Welte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zacharowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Meybohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5544-9647","authenticated-orcid":false,"given":"Jochen","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Dieter","family":"Walmrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-623X","authenticated-orcid":false,"given":"Khodr","family":"Tello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-9783","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Vad\u00e1sz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Malainou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kuznetsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Matt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1959-7295","authenticated-orcid":false,"given":"Janina","family":"Trauth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-0894","authenticated-orcid":false,"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Lohmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"2026092101451234000_12.5.01795-2025.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"2026092101451234000_12.5.01795-2025.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.5669"},{"key":"2026092101451234000_12.5.01795-2025.3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2213-2600(14)70097-9","article-title":"Subphenotypes 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