Lower Vitamin D During Acute Exacerbation Is Associated with Very Severe Chronic Obstructive Pulmonary Disease

<i>Background and Objectives</i>: Vitamin D deficiency is linked to adverse outcomes in chronic obstructive pulmonary disease (COPD). Limited data exist on how vitamin D levels vary by disease severity during acute exacerbations of COPD (AECOPDs). This study aimed to determine whether the vitamin D status during AECOPDs-alongside inflammatory and hematological biomarkers-is associated with COPD severity. <i>Materials and Methods</i>: This observational study included 105 AECOPD hospitalized patients, stratified according to GOLD stages 1-2, 3, and 4. Blood samples were collected to measure serum vitamin D-as 25-hydroxyvitamin D [25(OH)D], acute phase reactants, serum calcium, and selected hematological parameters. Inter-group differences were evaluated using Kruskal-Wallis tests, with Spearman correlations applied for intra-strata associations. ROC analysis and logistic regression assessed the discriminatory power of significant biomarkers. <i>Results</i>: C-reactive protein (CRP) and fibrinogen concentrations were elevated across all COPD stages, whereas calcium and vitamin D remained consistently below normal. Interleukin (IL)-6 and 25(OH)D levels varied significantly with COPD stage (<i>p</i> = 0.033 and <i>p</i> = 0.047, respectively), with a marked drop from GOLD stage 3 to stage 4. High-IL-6 patients revealed significantly elevated CRP (<i>p</i> = 0.045), erythrocyte sedimentation rate (ESR) (<i>p</i> = 0.032), fibrinogen (<i>p</i> = 0.011), and procalcitonin (<i>p</i> = 0.044). The strongest correlations were seen between CRP, ESR, and fibrinogen (<i>r_s</i> ≥ 0.58, <i>p</i> ≤ 0.05), indicating a coordinated acute-phase response that weakened with advancing disease. Serum 25(OH)D was a significant independent predictor of COPD severity (AUC = 0.631, <i>p</i> = 0.048), while IL-6 had a weaker predictive value, losing significance in the combined regression model. <i>Conclusions</i>: Vitamin D deficiency is more pronounced in very severe COPD, serving as a potential clinical indicator of disease severity during exacerbation episodes.