{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:18:16Z","timestamp":1769123896813,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In pulmonary sarcoidosis, alveolar macrophages (AMs) undergo epithelioid transformation, but their quantitative morphologic characteristics and association with systemic disease markers remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research question<\/jats:title>\n                    <jats:p>Do enlargement and activation features of AMs in bronchoalveolar lavage (BAL) samples correlate with systemic markers of sarcoidosis activity (ACE and sIL-2R)?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BAL cells from 16 biopsy-confirmed sarcoidosis cases and 4 healthy controls were cytocentrifuged, Diff-Quik\u00ae\u2013stained, and analyzed using a digital planimetric microscope. Cell area (CA) of 50 randomly selected AMs per subject (total\u202f=\u202f1,000) was quantified and categorized as small, medium, large, or extra-large based on control mean \u00b1 SD cutoffs. Nonparametric tests and principal component analysis (PCA) were applied to examine associations among CA, morphological features, serum ACE, and sIL-2R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean CA was 31% greater in sarcoidosis than in controls (368.2\u202f\u00b1\u202f169.3\u202f\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 281.4\u202f\u00b1\u202f90.9\u202f\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), with higher proportions of large\/extra-large AMs (41% vs. 14%;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Vacuolation, rosette formation, and membrane ruffling were hallmarks of AM activation, correlating strongly with serum ACE and sIL-2R but not with the BALF CD4\/CD8 ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AM enlargement and activation features are quantitative, reproducible surrogates of disease activity in pulmonary sarcoidosis. Clinical implications: Quantitative assessment of alveolar macrophage morphology may aid in assessment and monitoring of sarcoidosis activity and treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1739663","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:54:34Z","timestamp":1769064874000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enlarged, activated alveolar macrophages as quantitative surrogates of disease activity in pulmonary sarcoidosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Manabu","family":"Ishida","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Saraya","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutaka","family":"Kitamura","sequence":"additional","affiliation":[{"name":"GM-CSF Inhalation Promoting Organization","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koh","family":"Nakata","sequence":"additional","affiliation":[{"name":"GM-CSF Inhalation Promoting Organization","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruyuki","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S0272-5231(05)70411-1","article-title":"Descriptive definition and historic aspects of sarcoidosis","volume":"18","author":"James","year":"1997","journal-title":"Clin Chest Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1097\/MCP.0000000000000080","article-title":"Morbidity and mortality in sarcoidosis","volume":"20","author":"Gerke","year":"2014","journal-title":"Curr Opin Pulm Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1164\/ajrccm.160.2.ats4-99","article-title":"Statement on sarcoidosis","volume":"160","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3389\/fimmu.2013.00437","article-title":"Granuloma formation in pulmonary sarcoidosis","volume":"4","author":"Broos","year":"2013","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF02889023","article-title":"Sarcoid macrophage giant cells. 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