{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:27:43Z","timestamp":1792891663070,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"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>Background and Objectives: 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\u2014alongside inflammatory and hematological biomarkers\u2014is associated with COPD severity. Materials and Methods: This observational study included 105 AECOPD hospitalized patients, stratified according to GOLD stages 1\u20132, 3, and 4. Blood samples were collected to measure serum vitamin D\u2014as 25-hydroxyvitamin D [25(OH)D], acute phase reactants, serum calcium, and selected hematological parameters. Inter-group differences were evaluated using Kruskal\u2013Wallis tests, with Spearman correlations applied for intra-strata associations. ROC analysis and logistic regression assessed the discriminatory power of significant biomarkers. Results: 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 (p = 0.033 and p = 0.047, respectively), with a marked drop from GOLD stage 3 to stage 4. High-IL-6 patients revealed significantly elevated CRP (p = 0.045), erythrocyte sedimentation rate (ESR) (p = 0.032), fibrinogen (p = 0.011), and procalcitonin (p = 0.044). The strongest correlations were seen between CRP, ESR, and fibrinogen (rs \u2265 0.58, p \u2264 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, p = 0.048), while IL-6 had a weaker predictive value, losing significance in the combined regression model. Conclusions: Vitamin D deficiency is more pronounced in very severe COPD, serving as a potential clinical indicator of disease severity during exacerbation episodes.<\/jats:p>","DOI":"10.3390\/medicina61060979","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:46:26Z","timestamp":1748504786000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lower Vitamin D During Acute Exacerbation Is Associated with Very Severe Chronic Obstructive Pulmonary Disease"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1281-9862","authenticated-orcid":false,"given":"Larisa Alexandra","family":"Rus","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"},{"name":"Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly Nr. 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1192-1452","authenticated-orcid":false,"given":"Romana Olivia","family":"Pope\u021biu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"},{"name":"Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly Nr. 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-2691","authenticated-orcid":false,"given":"Simona Maria","family":"Borta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"},{"name":"Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly Nr. 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamaria","family":"V\u00eelcea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"},{"name":"Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly Nr. 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drago\u0219 Vasile","family":"Nica","sequence":"additional","affiliation":[{"name":"The National Institute of Research\u2014Development for Machines and Installations Designed for Agriculture and Food Industry (INMA), Bulevardul Ion Ionescu de la Brad 6, 013813 Bucure\u0219ti, Romania"},{"name":"Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-9155","authenticated-orcid":false,"given":"Teodor","family":"Vintil\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering of Animal Resources, University of Life Sciences \u201cKing Michael I of Romania\u201d from Timisoara, Calea Aradului 119, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stana Alina","family":"M\u0103ran","sequence":"additional","affiliation":[{"name":"Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly Nr. 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0071-9333","authenticated-orcid":false,"given":"Maria","family":"Pu\u0219chi\u021b\u0103","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pope\u021biu, R.O., Donath-Miklos, I., Borta, S.M., Rus, L.A., V\u00eelcea, A., Nica, D.V., and Pu\u0219chi\u021b\u0103, M. (2023). Serum YKL-40 levels, leukocyte profiles, and acute exacerbations of advanced COPD. J. Clin. Med., 12.","DOI":"10.3390\/jcm12186106"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.15585\/mmwr.mm6824a1","article-title":"Chronic obstructive pulmonary disease and smoking status\u2014United States, 2017","volume":"68","author":"Wheaton","year":"2019","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2346598","DOI":"10.1001\/jamanetworkopen.2023.46598","article-title":"Global burden of chronic obstructive pulmonary disease through 2050","volume":"6","author":"Boers","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"356","DOI":"10.21037\/jtd-23-646","article-title":"Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function","volume":"16","author":"Zheng","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.chest.2023.11.040","article-title":"National and local direct medical cost burden of COPD in the United States","volume":"165","author":"Mannino","year":"2024","journal-title":"Chest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1183","DOI":"10.1016\/S2214-109X(23)00217-6","article-title":"The global economic burden of chronic obstructive pulmonary disease for 204 countries and territories in 2020\u201350: A health-augmented macroeconomic modelling study","volume":"11","author":"Chen","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pratt, A.J., Purssell, A., Zhang, T., Luks, V.P., Bauza, X., Mulpuru, S., and Cowan, J. (2023). Complexity in clinical diagnoses of acute exacerbation of chronic obstructive pulmonary disease. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02587-1"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ahmad, R., Sarraj, B., and Razzaque, M.S. (2025). Vitamin D and mineral ion homeostasis: Endocrine dysregulation in chronic diseases. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1493986"},{"key":"ref_9","first-page":"997","article-title":"Vitamin D and the Lung","volume":"Volume 1","author":"Feldman","year":"2024","journal-title":"Feldman and Pike\u2019s Vitamin D"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lu, K., Tan, J.S., Li, T.Q., Yuan, J., Wang, H., and Wang, W. (2023). An inverse causal association between genetically predicted vitamin D and chronic obstructive pulmonary disease risk. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1111950"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/MCP.0000000000000935","article-title":"Vitamin D deficiency in chronic obstructive pulmonary disease","volume":"29","author":"Mullin","year":"2023","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_12","first-page":"e064136","article-title":"Vitamin D status and chronic obstructive pulmonary disease risk: A prospective UK biobank study","volume":"13","author":"Zhu","year":"2023","journal-title":"BMJ Open Respir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/crj.13310","article-title":"Vitamin D deficiency is associated with chronic obstructive pulmonary disease and exacerbation of COPD","volume":"15","author":"Lokesh","year":"2021","journal-title":"Clin. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.2147\/COPD.S101382","article-title":"The association between vitamin D and COPD risk, severity, and exacerbation: An updated systematic review and meta-analysis","volume":"11","author":"Zhu","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.trsl.2013.04.004","article-title":"Diet and vitamin D as risk factors for lung impairment and COPD","volume":"162","author":"Hanson","year":"2013","journal-title":"Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/COPD.S489650","article-title":"The role of severe vitamin D deficiency in predicting the risk of severe exacerbation in patients with chronic obstructive pulmonary disease","volume":"20","author":"Zhou","year":"2025","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.58675\/2682-339X.1922","article-title":"Study of the role of vitamin d deficiency in patients with acute exacerbation of chronic obstructive pulmonary disease","volume":"4","author":"Morsi","year":"2023","journal-title":"Al-Azhar Int. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4103\/ijrc.ijrc_48_19","article-title":"Baseline vitamin d as a predictor of mortality among hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease in an endemically vitamin D-deficient area in North India","volume":"9","author":"Bhat","year":"2020","journal-title":"Indian J. Respir. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.chest.2019.11.047","article-title":"Associations among 25-Hydroxyvitamin d levels, lung function, and exacerbation outcomes in COPD: An analysis of the SPIROMICS cohort","volume":"157","author":"Burkes","year":"2020","journal-title":"Chest"},{"key":"ref_20","first-page":"3961","article-title":"Vitamin D deficiency and COPD exacerbations: Effect of vitamin D supplementation","volume":"46","author":"Bellocchia","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12931-014-0131-0","article-title":"Severe vitamin D Deficiency is associated with frequent exacerbations and hospitalization in COPD patients","volume":"15","author":"Malinovschi","year":"2014","journal-title":"Respir. Res."},{"key":"ref_22","first-page":"CD013744","article-title":"Vitamin D for the management of chronic obstructive pulmonary disease","volume":"9","author":"Williamson","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"i6583","DOI":"10.1136\/bmj.i6583","article-title":"Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data","volume":"356","author":"Martineau","year":"2017","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1164\/rccm.201109-1644OC","article-title":"Vitamin D Levels and risk of acute exacerbations of chronic obstructive pulmonary disease: A prospective cohort study","volume":"185","author":"Kunisaki","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","first-page":"e43562","article-title":"How important is Vitamin D supplementation in the prevention of exacerbations in patients with chronic obstructive pulmonary disease (COPD): An evidence-based review","volume":"17","author":"Rocha","year":"2025","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/resp.12780","article-title":"Acute exacerbation of COPD","volume":"21","author":"Ko","year":"2016","journal-title":"Respirology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, Y.W.R., Leung, J.M., and Sin, D.D. (2016). A systematic review of diagnostic biomarkers of COPD exacerbation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158843"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7609083","DOI":"10.1155\/2022\/7609083","article-title":"Comparison of CRP, procalcitonin, neutrophil counts, eosinophil counts, sTREM-1, and OPN between pneumonic and nonpneumonic exacerbations in COPD patients","volume":"2022","author":"Mou","year":"2022","journal-title":"Can. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"239","DOI":"10.18295\/squmj.12.2022.062","article-title":"Haematological and inflammatory biomarkers among stable COPD and acute exacerbations of COPD patients","volume":"23","author":"Ramya","year":"2023","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.2147\/COPD.S361929","article-title":"Fibrinogen, a promising marker to evaluate severity and prognosis of acute exacerbation of chronic obstructive pulmonary disease: A retrospective observational study","volume":"17","author":"Sun","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.23937\/2378-3516\/1410109","article-title":"Seric markers and cell profile in blood and sputum in chronic obstructive pulmonary disease exacerbations (AECOPD)","volume":"6","author":"Gjerazi","year":"2019","journal-title":"Int. J. Respir. Pulm. Med."},{"key":"ref_32","first-page":"3996","article-title":"Fibrinogen and CRP biomarkers in patients with exacerbation of COPD group C and D","volume":"44","author":"Ilisie","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_33","first-page":"97","article-title":"The role of interleukin-6 signaling in development of systemic inflammation in chronic obstructive pulmonary disease","volume":"69","author":"Vitkina","year":"2018","journal-title":"Bull. Physiol. Pathol. Respir."},{"key":"ref_34","first-page":"13","article-title":"The significance of serum interleukin-8 in acute exacerbations of chronic obstructive pulmonary disease","volume":"17","author":"Zhang","year":"2018","journal-title":"Tanaffos"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.12659\/MSM.896458","article-title":"Plasma inflammatory cytokine IL-4, IL-8, IL-10, and TNF-\u03b1 levels correlate with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome","volume":"22","author":"Huang","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"00318","DOI":"10.1183\/23120541.00068-2021","article-title":"Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease","volume":"7","author":"Balasubramanian","year":"2021","journal-title":"ERJ Open Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.2147\/IJGM.S312045","article-title":"Prognostic value of neutrophil: Lymphocyte and platelet: Lymphocyte ratios for 28-day mortality of patients with AECOPD","volume":"14","author":"Luo","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2147\/COPD.S435921","article-title":"Predictive role of white blood cell differential count for the development of acute exacerbation in Korean chronic obstructive pulmonary disease","volume":"19","author":"Yoon","year":"2024","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_39","first-page":"e37482","article-title":"Serum electrolytes in patients presenting with acute exacerbation of chronic obstructive pulmonary disease (COPD) and their comparison with stable COPD Patients","volume":"15","author":"Deep","year":"2023","journal-title":"Cureus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/00325481.2019.1585689","article-title":"Correlation between hypocalcemia and acute exacerbation of chronic obstructive pulmonary disease in the elderly","volume":"131","author":"Qin","year":"2019","journal-title":"Postgrad. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"545","DOI":"10.14740\/jocmr3458w","article-title":"The use of serum procalcitonin as a diagnostic and prognostic biomarker in chronic obstructive pulmonary disease exacerbations: A literature review update","volume":"10","author":"Pantzaris","year":"2018","journal-title":"J. Clin. Med. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Qiyuan, P., Changyang, L., Gaigai, L., Ju, Q., and Xun, Z. (2024). Prognostic value of procalcitonin in acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0312099"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/1573398X19666230315124509","article-title":"Comparison of serum procalcitonin levels between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and patients with chronic obstructive pulmonary disease","volume":"19","author":"Behzadi","year":"2023","journal-title":"Curr. Respir. Med. Rev."},{"key":"ref_44","unstructured":"(2025, April 26). Spitalului Clinic Jude\u021bean de Urgen\u021b\u0103 Arad. Available online: https:\/\/www.scjarad.ro\/pneumologie-i\/."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Grelus, A., Nica, D.V., Miklos, I., Belengeanu, V., Ioiart, I., and Popescu, C. (2017). Clinical significance of measuring global hydroxymethylation of white blood cell DNA in prostate cancer: Comparison to psa in a pilot exploratory study. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112465"},{"key":"ref_46","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (2025, April 04). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Available online: https:\/\/goldcopd.org\/wp-content\/uploads\/2023\/03\/GOLD-2023-ver-1.3-17Feb2023_WMV.pdf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1183\/20734735.012717","article-title":"The Global Lung Function Initiative (GLI) network: Bringing the world\u2019s respiratory reference values together","volume":"13","author":"Cooper","year":"2017","journal-title":"Breathe"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Song, F., and Bachmann, M.O. (2016). Cumulative subgroup analysis to reduce waste in clinical research for individualised medicine. BMC Med., 14.","DOI":"10.1186\/s12916-016-0744-x"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Georgescu, M., Dr\u0103ghici, G.A., Oancea, E.F., Dehelean, C.A., \u015eoica, C., Vl\u0103du\u0163, N.V., and Nica, D.V. (2021). Effects of cadmium sulfate on the brown garden snail Cornu aspersum: Implications for DNA Methylation. Toxics, 9.","DOI":"10.3390\/toxics9110306"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103243","DOI":"10.1016\/j.etap.2019.103243","article-title":"Soil copper uptake by land snails: A semi-field experiment with juvenile Cantareus aspersus snails","volume":"72","author":"Dehelean","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32773","DOI":"10.1007\/s11356-021-17905-5","article-title":"The association between tobacco smoke exposure and vitamin D levels among US general population, 2001\u20132014: Temporal variation and inequalities in population susceptibility","volume":"29","author":"Yuan","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"160064","DOI":"10.1016\/j.scitotenv.2022.160064","article-title":"Trends in urban air pollution over the last two decades: A global perspective","volume":"858","author":"Sicard","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nieri, D., Daniele, M., Lombardi, S., Bazzan, E., Santerini, S., De Cusatis, G., and Neri, T. (2021). Circulating extracellular vesicles are associated with disease severity and interleukin-6 levels in COPD: A pilot study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215014"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yadav, R.S., Kant, S., Tripathi, P.M., Pathak, A.K., and Mahdi, A.A. (2022). Transcript levels of COX-2, TNF-\u03b1, IL-6 and IL-10 in chronic obstructive pulmonary disease: An association with smoking and severity. Res. J. Biotechnol., 17.","DOI":"10.25303\/1710rjbt90097"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2018.01.004","article-title":"Correlation of severity of chronic obstructive pulmonary disease with potential biomarkers","volume":"196","author":"Singh","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"575","DOI":"10.4103\/ejb.ejb_50_19","article-title":"Assessment of serum interleukin 6 level in patients with chronic obstructive pulmonary disease: Is it related to disease severity?","volume":"13","author":"Mostafa","year":"2019","journal-title":"Egypt. J. Bronchol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1199","DOI":"10.7717\/peerj.1199","article-title":"Association between serum interleukin-6 concentrations and chronic obstructive pulmonary disease: A systematic review and meta-analysis","volume":"3","author":"Wei","year":"2015","journal-title":"PeerJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"735","DOI":"10.2147\/COPD.S64135","article-title":"Interleukin-6 and interleukin-8 blood levels\u2019 poor association with the severity and clinical profile of ex-smokers with COPD","volume":"9","author":"Rabahi","year":"2014","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5114\/pja.2025.147674","article-title":"Inflammatory process: Factors inducing inflammation, forms and manifestations of inflammation, immunological significance of the inflammatory reaction","volume":"12","year":"2025","journal-title":"Alergol. Pol.-Pol. J. Allergol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mulvanny, A., Pattwell, C., Beech, A., Southworth, T., and Singh, D. (2022). Validation of sputum biomarker immunoassays and cytokine expression profiles in COPD. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081949"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1183\/09031936.06.00027705","article-title":"Variability of bronchial inflammation in chronic obstructive pulmonary disease: Implications for study design","volume":"27","author":"Gamble","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Xiong, X.F., Zhu, M., Wu, H.X., Wu, Z.H., Fan, L.L., and Cheng, D.Y. (2025). T-cell immune status in patients with acute exacerbation of chronic obstructive pulmonary disease: A case-control study. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1433844"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"170045","DOI":"10.1183\/16000617.0045-2017","article-title":"Immune Checkpoints in Chronic Obstructive Pulmonary Disease","volume":"26","author":"Wilkinson","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.2147\/COPD.S89763","article-title":"Vitamin D deficiency is associated with the severity of COPD: A systematic review and meta-analysis","volume":"10","author":"Zheng","year":"2015","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"00640-02023","DOI":"10.1183\/23120541.00314-2023","article-title":"The Association of weather conditions with day-to-day variability in physical activity in patients with COPD","volume":"9","author":"Blondeel","year":"2023","journal-title":"ERJ Open Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.2147\/COPD.S334228","article-title":"Update on the etiology, assessment, and management of COPD cachexia: Considerations for the clinician","volume":"17","author":"Beijers","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_67","first-page":"1315","article-title":"Does corticosteroid intake increase the risk of vitamin D deficiency in Tunisia\u2019s COPD patients?","volume":"62","author":"Mjid","year":"2023","journal-title":"Afr. Health Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4049\/jimmunol.2000964","article-title":"Low vitamin D status is associated with inflammation in patients with chronic obstructive pulmonary disease","volume":"206","author":"Fu","year":"2021","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Fang, L., Liu, K., Liu, C., Wang, X., Ma, W., Xu, W., and Sun, C. (2022). Tumor Accomplice: T cell exhaustion induced by chronic inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.979116"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4103\/rcm.rcm_60_23","article-title":"Vitamin D attenuates cardiac hypertrophy in rats through mRNA Regulation of interleukin-6 and its receptor","volume":"12","author":"Nikkholgh","year":"2023","journal-title":"Res. Cardiovasc. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"149.e1","DOI":"10.1016\/j.ajog.2013.09.037","article-title":"The Relationship of hypovitaminosis D and IL-6 in preeclampsia","volume":"210","author":"Xu","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lanser, L., Fuchs, D., Kurz, K., and Weiss, G. (2021). Physiology and inflammation driven pathophysiology of iron homeostasis\u2014Mechanistic insights into anemia of inflammation and its treatment. Nutrients, 13.","DOI":"10.3390\/nu13113732"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Iamartino, L., and Brandi, M.L. (2022). The calcium-sensing receptor in inflammation: Recent updates. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1059369"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6603","DOI":"10.2147\/JIR.S478568","article-title":"Inflammatory and immune mechanisms in COPD: Current status and therapeutic prospects","volume":"17","author":"Qi","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/0962280211403598","article-title":"Sensible Use of Observational Clinical Data","volume":"22","author":"Overhage","year":"2013","journal-title":"Stat. Methods Med. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/6\/979\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:40Z","timestamp":1760031640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/6\/979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["medicina61060979"],"URL":"https:\/\/doi.org\/10.3390\/medicina61060979","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}