{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:42Z","timestamp":1792790442555,"version":"4.5.0"},"reference-count":34,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82502168"],"award-info":[{"award-number":["82502168"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Huzhou Municipal Science and Technology Bureau","award":["2021GZ62"],"award-info":[{"award-number":["2021GZ62"]}],"id":[{"id":"https:\/\/ror.org\/00anpmf82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Science and Technology Project of Deqing County","award":["2022SK02"],"award-info":[{"award-number":["2022SK02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic inflammatory syndrome in which forced expiratory volume in 1 s expressed as a percentage of predicted value (FEV1% predicted) may dissociate from patient-reported symptom burden. This study evaluated an Integrated Inflammatory Profile Score (IIPS) as a potential biological correlate for a more holistic assessment of stable COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum concentrations of 11 cytokines were measured in 62 patients with stable COPD. The IIPS was derived using automated linear modeling with forward stepwise selection guided by the corrected Akaike information criterion (AICc). Associations of the IIPS with COPD Assessment Test (CAT) scores were compared with those of FEV1% predicted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The optimized IIPS, comprising interferon-gamma (IFN-\u03b3), interleukin-2 (IL-2), and interleukin-10 (IL-10), was significantly associated with FEV1% predicted (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.1867,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0005) and outperformed the individual cytokines in discriminating spirometric severity (area under the receiver operating characteristic curve (AUC) = 0.7381). For symptom burden, FEV1% predicted showed greater explanatory power for exertional domains, particularly breathlessness (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.0832) and activities (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.1280). By contrast, the IIPS showed numerically stronger trend-level associations for sleep (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.0519,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0750) and energy (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.0511,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0773), although these associations did not reach conventional statistical significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The IIPS reflects Global Initiative for Chronic Obstructive Lung Disease (GOLD)-defined physiological severity more effectively than any single cytokine measured in this study. Its associations with patient-reported systemic symptoms were modest and exploratory, suggesting that integrated inflammatory profiling may complement spirometry in characterizing COPD burden but requires external and longitudinal validation before clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21751","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:15:24Z","timestamp":1790842524000},"page":"e21751","source":"Crossref","is-referenced-by-count":0,"title":["A serum cytokine-derived integrated inflammatory profile score (IIPS) links systemic inflammation to symptom burden and severity in COPD"],"prefix":"10.7717","volume":"14","author":[{"given":"Jiexun","family":"Cai","sequence":"first","affiliation":[{"name":"Deqing People\u2019s Hospital and The Affiliated Deqing Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Li","sequence":"additional","affiliation":[{"name":"Deqing People\u2019s Hospital and The Affiliated Deqing Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Huzhou College, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangli","family":"An","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang, China"},{"name":"The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Deqing People\u2019s Hospital and The Affiliated Deqing Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Han","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Deqing People\u2019s Hospital and The Affiliated Deqing Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-2021","authenticated-orcid":true,"given":"Yunliang","family":"Yao","sequence":"additional","affiliation":[{"name":"Deqing People\u2019s Hospital and The Affiliated Deqing Hospital, Huzhou University, Huzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"2","key":"10.7717\/peerj.21751\/ref-1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1183\/09031936.03.00405703","article-title":"Systemic effects of chronic obstructive pulmonary disease","volume":"21","author":"Agust\u00ed","year":"2003","journal-title":"European Respiratory Journal"},{"issue":"5","key":"10.7717\/peerj.21751\/ref-2","doi-asserted-by":"publisher","first-page":"e37483","DOI":"10.1371\/journal.pone.0037483","article-title":"Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype","volume":"7","author":"Agust\u00ed","year":"2012","journal-title":"PLOS ONE"},{"issue":"2","key":"10.7717\/peerj.21751\/ref-3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3109\/13547500903311902","article-title":"Effects of inhaled therapy on biomarkers of systemic inflammation in stable chronic obstructive pulmonary disease","volume":"15","author":"Antoniu","year":"2010","journal-title":"Biomarkers"},{"issue":"7","key":"10.7717\/peerj.21751\/ref-4","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.4103\/jfmpc.jfmpc_347_19","article-title":"Clinical, demographic and radiological profile of smoker COPD versus nonsmoker COPD patients at a tertiary care center in North India","volume":"8","author":"Bajpai","year":"2019","journal-title":"Journal of Family Medicine and Primary Care"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory mechanisms in patients with chronic obstructive pulmonary disease","volume":"138","author":"Barnes","year":"2016","journal-title":"Journal of Allergy and Clinical Immunology"},{"issue":"5","key":"10.7717\/peerj.21751\/ref-6","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1183\/09031936.00128008","article-title":"Systemic manifestations and comorbidities of COPD","volume":"33","author":"Barnes","year":"2009","journal-title":"European Respiratory Journal"},{"issue":"6","key":"10.7717\/peerj.21751\/ref-7","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1164\/rccm.202303-0450OC","article-title":"FEV1\/FVC severity stages for chronic obstructive pulmonary disease","volume":"208","author":"Bhatt","year":"2023","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"16","key":"10.7717\/peerj.21751\/ref-8","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.12114\/j.issn.1007-9572.2024.0588","article-title":"Interpretation of global strategy for the diagnosis, treatment, management and prevention of chronic obstructive pulmonary disease 2025 report","volume":"28","author":"Chen","year":"2025","journal-title":"Chinese General Practice"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-9","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/1465-9921-12-146","article-title":"COPD association and repeatability of blood biomarkers in the ECLIPSE cohort","volume":"12","author":"Dickens","year":"2011","journal-title":"Respiratory Research"},{"issue":"6","key":"10.7717\/peerj.21751\/ref-10","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1373\/clinchem.2008.120717","article-title":"Measurement and quality control issues in multiplex protein assays: a case study","volume":"55","author":"Ellington","year":"2009","journal-title":"Clinical Chemistry"},{"issue":"7","key":"10.7717\/peerj.21751\/ref-11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1136\/thx.2003.019588","article-title":"Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis","volume":"59","author":"Gan","year":"2004","journal-title":"Thorax"},{"issue":"Suppl. 4","key":"10.7717\/peerj.21751\/ref-12","doi-asserted-by":"publisher","first-page":"S234","DOI":"10.1513\/AnnalsATS.201808-533MG","article-title":"Targeting chronic obstructive pulmonary disease phenotypes, endotypes, and biomarkers","volume":"15","author":"Garudadri","year":"2018","journal-title":"Annals of the American Thoracic Society"},{"key":"10.7717\/peerj.21751\/ref-13","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.2147\/COPD.S156135","article-title":"Chinese version of the severe respiratory insufficiency questionnaire for patients with COPD receiving long-term oxygen therapy","volume":"13","author":"Guan","year":"2018","journal-title":"International Journal of Chronic Obstructive Pulmonary Disease"},{"issue":"4","key":"10.7717\/peerj.21751\/ref-14","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1183\/09031936.00025214","article-title":"The COPD assessment test: a systematic review","volume":"44","author":"Gupta","year":"2014","journal-title":"European Respiratory Journal"},{"issue":"12","key":"10.7717\/peerj.21751\/ref-15","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.3390\/diagnostics10121029","article-title":"Combination of Systemic inflammatory biomarkers in assessment of chronic obstructive pulmonary disease: diagnostic performance and identification of networks and clusters","volume":"10","author":"Hlapcic","year":"2020","journal-title":"Diagnostics"},{"issue":"4","key":"10.7717\/peerj.21751\/ref-16","doi-asserted-by":"publisher","first-page":"289","DOI":"10.4046\/trd.2022.0074","article-title":"Long-term outcome of chronic obstructive pulmonary disease: a review","volume":"85","author":"Jo","year":"2022","journal-title":"Tuberculosis and Respiratory Diseases"},{"issue":"3","key":"10.7717\/peerj.21751\/ref-17","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1183\/09031936.00102509","article-title":"Development and first validation of the COPD assessment test","volume":"34","author":"Jones","year":"2009","journal-title":"European Respiratory Journal"},{"issue":"2","key":"10.7717\/peerj.21751\/ref-18","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1378\/chest.130.2.326","article-title":"Systemic inflammation in patients with COPD and pulmonary hypertension","volume":"130","author":"Joppa","year":"2006","journal-title":"Chest"},{"issue":"3","key":"10.7717\/peerj.21751\/ref-19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1159\/000336549","article-title":"Health status assessment in routine clinical practice: the chronic obstructive pulmonary disease assessment test score in outpatients","volume":"84","author":"Kelly","year":"2012","journal-title":"Respiration"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-20","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s40169-015-0068-z","article-title":"Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer","volume":"4","author":"King","year":"2015","journal-title":"Clinical and Translational Medicine"},{"issue":"2","key":"10.7717\/peerj.21751\/ref-21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1411532","article-title":"Lung-function trajectories leading to chronic obstructive pulmonary disease","volume":"373","author":"Lange","year":"2015","journal-title":"The New England Journal of Medicine"},{"issue":"1st World Lung Disease Summit","key":"10.7717\/peerj.21751\/ref-22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2147\/COPD.S85976","article-title":"Diagnosis, assessment, and phenotyping of COPD: beyond FEV1","volume":"11","author":"Lange","year":"2016","journal-title":"International Journal of Chronic Obstructive Pulmonary Disease"},{"issue":"9","key":"10.7717\/peerj.21751\/ref-23","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1136\/thx.2006.061648","article-title":"Standardisation of lung function testing: helpful guidance from the ATS\/ERS task force","volume":"61","author":"Laszlo","year":"2006","journal-title":"Thorax"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-24","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12931-025-03250-5","article-title":"Multi-omics characterization of early chronic obstructive pulmonary disease","volume":"26","author":"Li","year":"2025","journal-title":"Respiratory Research"},{"issue":"3","key":"10.7717\/peerj.21751\/ref-25","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/s0091-6749(99)70471-9","article-title":"Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease","volume":"103","author":"Majori","year":"1999","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"10.7717\/peerj.21751\/ref-26","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.rmed.2019.03.007","article-title":"Determinants of CAT (COPD assessment test) scores in a population of patients with COPD in central and Eastern Europe: the POPE study","volume":"150","author":"Miravitlles","year":"2019","journal-title":"Respiratory Medicine"},{"issue":"10","key":"10.7717\/peerj.21751\/ref-27","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1016\/j.mayocp.2018.05.026","article-title":"COPD guidelines: a review of the 2018 GOLD report","volume":"93","author":"Mirza","year":"2018","journal-title":"Mayo Clinic Proceedings"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-28","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1465-9921-7-125","article-title":"Role of TNF\u03b1 in pulmonary pathophysiology","volume":"7","author":"Mukhopadhyay","year":"2006","journal-title":"Respiratory Research"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1465-9921-13-71","article-title":"Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD","volume":"13","author":"Pinto-Plata","year":"2012","journal-title":"Respiratory Research"},{"issue":"7","key":"10.7717\/peerj.21751\/ref-30","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1136\/thx.2006.064428","article-title":"Profiling serum biomarkers in patients with COPD: associations with clinical parameters","volume":"62","author":"Pinto-Plata","year":"2007","journal-title":"Thorax"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4103\/ijp.ijp_970_24","article-title":"Breathing insights: biomarkers as tools for chronic obstructive pulmonary disease assessment: a systematic review","volume":"58","author":"Singh","year":"2026","journal-title":"Indian Journal of Pharmacology"},{"key":"10.7717\/peerj.21751\/ref-32","doi-asserted-by":"publisher","first-page":"1032786","DOI":"10.3389\/fphys.2023.1032786","article-title":"The correlation between a Th1\/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results","volume":"14","author":"Tang","year":"2023","journal-title":"Frontiers in Physiology"},{"issue":"12","key":"10.7717\/peerj.21751\/ref-33","doi-asserted-by":"publisher","first-page":"987","DOI":"10.2217\/bmm-2020-0770","article-title":"Pre-analytical sample handling effects on blood cytokine levels: quality control of a COVID-19 biobank","volume":"15","author":"Verberk","year":"2021","journal-title":"Biomarkers in Medicine"},{"issue":"1","key":"10.7717\/peerj.21751\/ref-34","doi-asserted-by":"publisher","first-page":"2525433","DOI":"10.1080\/15412555.2025.2525433","article-title":"Lung function decline in COPD\u2014relations to changes in symptom burden, inflammation, and comorbidities","volume":"22","author":"Wang","year":"2025","journal-title":"COPD: Journal of Chronic Obstructive Pulmonary Disease"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/21751.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/21751.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/21751.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/21751.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:15:29Z","timestamp":1790842529000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/21751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":34,"alternative-id":["10.7717\/peerj.21751"],"URL":"https:\/\/doi.org\/10.7717\/peerj.21751","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"e21751"}}