{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:24:55Z","timestamp":1790702695244,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>Peripheral blood cell counts are useful biomarkers in COPD, but may not fully reflect disease activity. The Sysmex XN\u2010Series haematology analyser offers advanced measurements of immune cell populations, providing information about the number and activation status of peripheral blood cells. We hypothesized that assessing immune cell activation status, in addition to cell counts, could provide complementary insights into the clinical heterogeneity of severe COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For this study, 499 extensively characterised patients with severe COPD were included from the Groningen Severe COPD cohort. A total of 24 Sysmex\u2010derived systemic blood parameters were selected for analysis. Clustering of blood cell population data was performed using Self\u2010Organising Maps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cell population parameters showed various associations with clinical characteristics, such as emphysema severity and lung function. Four clusters were identified based on their inflammatory profiles, each showing distinct clinical characteristics: the \u2018normal cell counts, resting pattern\u2019 cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009156) showed high emphysema severity scores and RV\/TLC ratios; the \u2018normal cell counts, activated pattern\u2019 cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009241) was associated with few exacerbations; the \u2018elevated cell counts, activated pattern\n                      <jats:italic>\u2019<\/jats:italic>\n                      cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200997) displayed high inflammatory cell counts and activity along with high exacerbation rates; and the small \u2018\n                      <jats:italic>low\u2010eosinophilic\u2019<\/jats:italic>\n                      cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) was characterised by inactive circulating eosinophils.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cell population data can be used to identify distinct inflammatory profiles with clinical relevance in severe COPD. Cell population data provide information beyond absolute cell counts, supporting the added value of including activation markers in COPD phenotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      NCT04023409 at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/resp70146-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/resp.70146","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T04:28:55Z","timestamp":1760934535000},"page":"141-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Clinically Distinct Clusters in Patients With Severe\n                    <scp>COPD<\/scp>\n                    Using Circulating Blood Cell Population Parameters"],"prefix":"10.1002","volume":"31","author":[{"given":"Pauline J. M.","family":"Kuks","sequence":"first","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-9673","authenticated-orcid":false,"given":"Jorine E.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Else A. M. D.","family":"ter Haar","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Joost","family":"van Pelt","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk\u2010Jan","family":"Slebos","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"van den Berge","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-8061","authenticated-orcid":false,"given":"Simon D.","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Global Strategy for the Diagnosis Management and Prevention of COPD \u201cGOLD Report 2024 [Internet]. Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for the Diagnosis Management and Prevention of Chronic Obstructive Pulmonary Disease (2024). 2024. p. 206\u201d https:\/\/goldcopd.org\/2024\u2010gold\u2010report\/."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12642"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(12)70060-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2003.019588"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037483"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01436-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S170353"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30217-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1268-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00838-2020"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.05.011"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S176122"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12254"},{"issue":"3","key":"e_1_2_10_15_1","first-page":"235","article-title":"Detection and Quantification of Hypo\u2010 and Hypergranulated Neutrophils on the New Sysmex XN Hematology Analyzer: Establishment of an Adapted Reference Interval for the Neutrophil\u2010Granularity\u2010Intensity Compared to XE\u2010Technology in Adult Patients","volume":"61","author":"Zimmermann M.","year":"2015","journal-title":"Clinical Laboratory"},{"key":"e_1_2_10_16_1","unstructured":"\u201cNovel Haematological Parameters for Rapidly Monitoring the Immune System Response\u201d."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12562"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092332"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12261"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13697"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00268\u20102024"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2022-0094"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406223251314286"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13061299"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.04.066"},{"issue":"2","key":"e_1_2_10_26_1","first-page":"355","article-title":"Recombinant Human Eosinophil\u2010Derived Neurotoxin (rhEDN) is an Effective Antiviral Agent Against Respiratory Syncytial Virus in Vitro","volume":"25","author":"Domachowske J. 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