{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T18:03:43Z","timestamp":1771956223092,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Objective: Acute exacerbations (AECOPD) are primary determinants of clinical instability in chronic obstructive pulmonary disease (COPD), and the \u201cfrequent exacerbator\u201d (\u22652\/year) phenotype markedly increases morbidity and healthcare utilization. In this study, we evaluated the association between the Systemic Immune-Inflammation Index (SII), calculated from routine hemogram parameters during the stable period, and the occurrence of frequent exacerbations within the subsequent 1 year, and aimed to define a clinically applicable SII threshold (cut-off). Materials and Methods: In this retrospective observational cohort study conducted at a tertiary care center, patients who attended the outpatient clinic between January 2020 and February 2025 and had COPD confirmed by post-bronchodilator spirometric criteria (FEV1\/FVC &lt; 70%) were identified through electronic medical records. The index date was defined as a routine outpatient visit during stable COPD; patients were followed for AECOPD for 365 days after the index date. The stable period was defined as a visit occurring \u22654 weeks after the last exacerbation and without signs of acute infection. Patients with positive COVID-19 PCR results were excluded due to the uncertainty in distinguishing exacerbation from COVID-19. The primary endpoint was the development of frequent exacerbations (\u22652 AECOPD) within 365 days. AECOPD was defined as an acute worsening of dyspnea, cough, and\/or sputum requiring additional pharmacotherapy (systemic corticosteroids and\/or antibiotics). SII, NLR, PLR, LMR, and PPN were calculated using hemogram parameters. Groups (&lt;2 vs. \u22652 exacerbations) were compared; a ROC\u2013Youden analysis was performed to determine cut-offs. After ROC-based dichotomization, univariate and multivariable logistic regression analyses were used to evaluate associations; multicollinearity was assessed using the VIF. To address potential optimism bias, diagnostic performance metrics (AUC, sensitivity, specificity) were internally validated using 1000 stratified bootstrap replicates. Results: A total of 159 patients were included. The cohort was predominantly male (91.2%). Demographic characteristics and most spirometric parameters were similar between groups; a trend toward lower absolute FVC was observed in the \u22652 exacerbation group (p = 0.051). Platelet counts were higher in the \u22652 exacerbation group (p = 0.029). In the ROC analysis, AUC values ranged from 0.505 to 0.591 across indices. For the SII, the AUC was 0.591 (95% CI: 0.500\u20130.677; p = 0.049), and the optimal cut-off was 1082.79. The LMR cut-off was 1.76; however, the LMR did not demonstrate statistically significant discriminatory performance in the ROC analysis (AUC 0.535; p = 0.448). In univariate analyses, SII &gt; 1082.79 (OR = 3.028, 95% CI: 1.522\u20136.027; p = 0.002) was associated with frequent exacerbations. In a multivariable logistic regression adjusted for cardiovascular disease and overall comorbidity status, SII &gt; 1082.79 remained independently associated (OR = 3.029, 95% CI: 1.485\u20136.179; p = 0.002). Other hemogram-derived indices did not retain independent prognostic significance in this outpatient cohort. Conclusion: SII measured during stable COPD was independently associated with frequent exacerbations over the subsequent 1 year. The SII &gt; 1082.79 threshold may offer a practical risk stratification approach to flag \u201chigh-risk\u201d patients in outpatient care. However, given the modest discriminative performance and the single-cohort derivation, this cut-off should be considered exploratory despite the use of bootstrap internal validation. Because this was a single-center study with a predominantly male cohort, the generalizability\u2014particularly to female patients and other settings\u2014requires prospective external validation.<\/jats:p>","DOI":"10.3390\/medicina62030429","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T16:58:18Z","timestamp":1771952298000},"page":"429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Clinical Cut-Off Value for the Systemic Immune-Inflammation Index to Predict Frequent Exacerbations in Stable COPD"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-3333","authenticated-orcid":false,"given":"Ozlem","family":"Sengoren Dikis","sequence":"first","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4274-0333","authenticated-orcid":false,"given":"Ceren","family":"Degirmenci","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Mu\u011fla Research and Training Hospital, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-5813","authenticated-orcid":false,"given":"Sabri Serhan","family":"Olcay","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-7187","authenticated-orcid":false,"given":"Fulden Cantas","family":"Turkis","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hacer Aybike","family":"Toptas Ogut","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-9233","authenticated-orcid":false,"given":"Utku","family":"Tapan","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0935-5927","authenticated-orcid":false,"given":"Fatih","family":"Alasan","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozge","family":"Oral Tapan","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/S2213-2600(24)00413-2","article-title":"GOLD COPD report: 2025 update","volume":"13","author":"Venkatesan","year":"2025","journal-title":"Lancet Respir. 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