{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:16:23Z","timestamp":1783419383667,"version":"3.54.6"},"reference-count":24,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Sarcoidosis is a multisystem inflammatory disease characterized by heterogeneous clinical manifestations and variable disease severity. Hematological inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and systemic immune-inflammation index (SII), have recently attracted attention as accessible indicators of systemic inflammation in sarcoidosis. This study aimed to evaluate radiological stage, symptom burden, pulmonary function parameters, and hematological markers in patients with sarcoidosis. Methods: This retrospective multicenter cohort study included histopathologically confirmed sarcoidosis patients from 10 centers. Demographic characteristics, clinical manifestations, pulmonary function test parameters, serum angiotensin-converting enzyme (ACE) levels, and hematological inflammatory markers (MPV, RDW, NLR, PLR, SII) were evaluated. Patients were categorized according to radiological stage (stage 0\u2013I vs. stage II\u2013IV), symptomatic status, and symptom burden (&lt;3 vs. \u22653 symptoms). Results: Among 458 patients included in the study, stage I (47.8%) and stage II (46.9%) disease were the predominant radiological presentations. Patients with stage II\u2013IV disease were older and demonstrated significantly lower forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1\/FVC ratio, and diffusing capacity for carbon monoxide (DLCO) values together with higher serum ACE levels compared with stage 0\u2013I disease. Dyspnea, weight loss, and extrapulmonary involvement were more frequent in stage 2\u20134 disease. No significant associations were observed between radiological stage and NLR, PLR, or SII values. MPV and RDW values differed significantly between symptomatic and asymptomatic patients. Patients with \u22653 symptoms demonstrated significantly lower pulmonary function parameters together with statistically significant higher NLR, PLR, and SII values. In multivariate analyses, only the SII demonstrated an independent association with a high symptom burden. Conclusions: Serum ACE levels were associated with advanced radiological stage, whereas hemogram-derived inflammatory indices, particularly the NLR, PLR, and SII, were associated with symptom burden rather than radiological stage in sarcoidosis and may reflect symptomatic inflammatory activity.<\/jats:p>","DOI":"10.3390\/diagnostics16132082","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:48:32Z","timestamp":1782992912000},"page":"2082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of Systemic Immune-Inflammation Index and Hematological Markers with Symptom Burden and Radiological Stage in Sarcoidosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-3338","authenticated-orcid":false,"given":"Ezgi","family":"Erdem T\u00fcre","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Etlik City Hospital, 06170 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-7615","authenticated-orcid":false,"given":"Berna","family":"Ak\u0131nc\u0131 \u00d6zy\u00fcrek","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Atat\u00fcrk Sanatoryum Training and Research Hospital, 06290 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-4390","authenticated-orcid":false,"given":"Fulsen","family":"Bozku\u015f","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Kahramanmara\u015f S\u00fct\u00e7\u00fc \u0130mam University, 46000 Kahramanmara\u015f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6160-3778","authenticated-orcid":false,"given":"Nilg\u00fcn","family":"Yilmaz Demirci","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-9551","authenticated-orcid":false,"given":"Celal","family":"Sat\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, 34020 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-7419","authenticated-orcid":false,"given":"Ayshan","family":"Mammadova","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1016-7336","authenticated-orcid":false,"given":"G\u00f6zde","family":"Kalbaran Kismet","sequence":"additional","affiliation":[{"name":"Clinic of Pulmonary Medicine, Sultan 2. Abdulhamid Han Training and Research Hospital, 34668\u00a0Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-6484","authenticated-orcid":false,"given":"Zeynep","family":"Erayman Ozen","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Atat\u00fcrk Sanatoryum Training and Research Hospital, 06290 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-4632","authenticated-orcid":false,"given":"Onur","family":"Yaz\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, 09010 Ayd\u0131n, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-2376","authenticated-orcid":false,"given":"\u015eule","family":"Ta\u015f G\u00fclen","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, 09010 Ayd\u0131n, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-1636","authenticated-orcid":false,"given":"Burcu","family":"Akk\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Kahramanmara\u015f S\u00fct\u00e7\u00fc \u0130mam University, 46000 Kahramanmara\u015f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8822-7944","authenticated-orcid":false,"given":"Ay\u015feg\u00fcl","family":"Erin\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, 34020 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-4636","authenticated-orcid":false,"given":"Nevin","family":"Fazl\u0131o\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Nam\u0131k Kemal University, 59030 Tekirda\u011f, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-7608","authenticated-orcid":false,"given":"Pelin P\u0131nar","family":"Deniz","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, \u00c7ukurova University, 01790 Adana, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-2365","authenticated-orcid":false,"given":"P\u0131nar","family":"Y\u0131ld\u0131z G\u00fclhan","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, D\u00fczce University, 81620 D\u00fczce, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-0767","authenticated-orcid":false,"given":"Yasemin","family":"S\u00f6yler","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Atat\u00fcrk Sanatoryum Training and Research Hospital, 06290 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-1322","authenticated-orcid":false,"given":"Aysun","family":"\u015eeng\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, Sakarya University, 54290 Sakarya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-019-0096-x","article-title":"Sarcoidosis","volume":"5","author":"Grunewald","year":"2019","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1136\/thoraxjnl-2019-214348","article-title":"BTS Clinical Statement on Pulmonary Sarcoidosis","volume":"76","author":"Thillai","year":"2021","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1136\/bmj.2.5261.1165","article-title":"Prognosis of Intrathoracic Sarcoidosis in England. A Review of 136 Cases after Five Years\u2019 Observation","volume":"2","author":"Scadding","year":"1961","journal-title":"Br. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e000357","DOI":"10.1136\/bmjresp-2018-000357","article-title":"Sarcoidosis in the UK: Insights from British Thoracic Society Registry Data","volume":"6","author":"Thillai","year":"2019","journal-title":"BMJ Open Respir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Erdem T\u00fcre, E., Ak\u0131nc\u0131 \u00d6zy\u00fcrek, B., Seyfettin \u00c7elik, E.P., Anar, C., Y\u0131lmaz Demirci, N., Co\u015fkun, F., and Okutan, O. (2026). From Guidelines to Reality: How Do Physicians Really Manage Sarcoidosis?. BMC Pulm. Med., 26.","DOI":"10.1186\/s12890-026-04226-x"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hu, X., Zou, L., Wang, S., Zeng, T., Li, P., Shen, Y., and Chen, L. (2022). Performance of Serum Angiotensin-Converting Enzyme in Diagnosing Sarcoidosis and Predicting the Active Status of Sarcoidosis: A Meta-Analysis. Biomolecules, 12.","DOI":"10.3390\/biom12101400"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/crj.12101","article-title":"Prognostic Value of Red Cell Distribution Width in Patients with Sarcoidosis","volume":"9","author":"Ozsu","year":"2015","journal-title":"Clin. Respir. J."},{"key":"ref_8","first-page":"e2023008","article-title":"Systematic Review of the Diagnostic Role of Neutrophil to Lymphocyte Ratio in Sarcoidosis","volume":"40","author":"Kalami","year":"2023","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2217\/bmm-2018-0252","article-title":"Predictive Value of Platelet-to-Lymphocyte Ratio in Patients with Sarcoidosis","volume":"13","author":"Karadeniz","year":"2019","journal-title":"Biomark. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10238-024-01294-3","article-title":"The Diagnostic Role of the Systemic Inflammation Index in Patients with Immunological Diseases: A Systematic Review and Meta-Analysis","volume":"24","author":"Mangoni","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Onyilmaz, T., Argun Baris, S., Kaya, H., Pehlivan, A.Z., Albayrak, H., Aktoprak, S.N., Boyaci, H., and Basyigit, I. (2025). Predictive Impact of Hematological and Biochemical Parameters on the Clinical Course of Sarcoidosis. Diagnostics, 15.","DOI":"10.3390\/diagnostics15192501"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105998","DOI":"10.1016\/j.rmed.2020.105998","article-title":"Clinical Features and Outcomes of Asymptomatic Pulmonary Sarcoidosis. A Comparative Cohort Study","volume":"169","author":"Iriarte","year":"2020","journal-title":"Respir. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00408-019-00206-7","article-title":"The Burden of Sarcoidosis Symptoms from a Patient Perspective","volume":"197","author":"Voortman","year":"2019","journal-title":"Lung"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1183\/09031936.00002512","article-title":"Sarcoidosis-Associated Fatigue","volume":"40","author":"Drent","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13023-024-03152-7","article-title":"Diagnostic Delay of Sarcoidosis: An Integrated Systematic Review","volume":"19","author":"Namsrai","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stjepanovic, M., Maric, N., Belic, S., Milin-Lazovic, J., Djurdjevic, N., Jankovic, J., Petrovic, M., Peric, J., Tulic, I., and Cvejic, J. (2024). Characteristics of Patients with Sarcoidosis with Emphasis on Acute vs. Chronic Forms-A Single Center Experience. J. Pers. Med., 14.","DOI":"10.3390\/jpm14060616"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12016-014-8450-y","article-title":"The Clinical Features of Sarcoidosis: A Comprehensive Review","volume":"49","author":"Judson","year":"2015","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rmed.2019.03.012","article-title":"Quantifying the Relationship between Symptoms at Presentation and the Prognosis of Sarcoidosis","volume":"152","author":"Judson","year":"2019","journal-title":"Respir. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/crj.12178","article-title":"The Clinical Significance of Hematologic Parameters in Patients with Sarcoidosis","volume":"10","author":"Dirican","year":"2016","journal-title":"Clin. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/00325481.2022.2082805","article-title":"The Utility of Neutrophil-to-Lymphocyte Ratio Determined at Initial Diagnosis in Predicting Disease Stage and Discriminating between Active and Stable Disease in Patients with Sarcoidosis: A Cross-Sectional Study","volume":"134","author":"Sonkaya","year":"2022","journal-title":"Postgrad. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/ejop.ejop_6_20","article-title":"Can Hematological Parameters Guide the Differentiation between Sarcoidosis and Tuberculous Lymphadenitis?","volume":"23","author":"Kerget","year":"2021","journal-title":"Eurasian J. Pulmonol."},{"key":"ref_22","first-page":"1696450","article-title":"The Association of Neutrophil\/Lymphocyte and Platelet\/Lymphocyte Ratios and Hematological Parameters with Diagnosis, Stages, Extrapulmonary Involvement, Pulmonary Hypertension, Response to Treatment, and Prognosis in Patients with Sarcoidosis","volume":"2020","author":"Korkmaz","year":"2020","journal-title":"Can. Respir. J."},{"key":"ref_23","first-page":"e2023038","article-title":"The Role of Systemic Immune-Inflammation Index (SII) in the Differential Diagnosis of Granulomatous and Reactive LAP Diagnosed by Endobronchial Ultrasonography","volume":"40","author":"Kerget","year":"2023","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.28982\/josam.7823","article-title":"Pan-Immune-Inflammation Value and Systemic Immune-Inflammation Index: Are They Useful Markers in Sarcoidosis? SII and PIV in Sarcoidosis","volume":"7","year":"2023","journal-title":"J. Surg. Med."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/13\/2082\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:48:13Z","timestamp":1783417693000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/13\/2082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":24,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["diagnostics16132082"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16132082","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]}}}