{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:25:14Z","timestamp":1788391514309,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Long-term non-invasive ventilation (LT-NIV) can prolong life expectancy and may reduce the number of exacerbations in patients with COPD. The eosinophilic phenotype has recently gained significant attention as a treatable trait in COPD. However, it is less known how this phenotype relates to exacerbations and mortality in patients who are set up on LT-NIV. Methods: A total of 191 patients with COPD (65 \u00b1 8 years, 55% women) who were setup on LT-NIV and followed-up (28\/15\u201349\/months) at our tertiary centre were analysed. The eosinophilic phenotype was defined by using an accepted cutoff for blood eosinophil count (\u2265300 cells\/\u00b5L). Results: A total of 37 patients had the eosinophilic phenotype (66 \u00b1 9 years, 60% women). There was a higher reduction in the number of exacerbations (1.0\/\u22121.0\u20133.2\/ vs. 0.05\/\u22121.4\u20131.63\/, p &lt; 0.01) and a trend for a reduction in the rate of hospitalisations (1.0\/\u22121.0\u20132.0\/ vs. 0.0\/0.0\u20131.0\/, p = 0.07) post-NIV setup in the eosinophilic group. Most importantly, patients with high eosinophil counts had longer overall survival (34\/15\u201374\/ vs. 28\/15\u201347\/ months, p = 0.02, adjusted for covariates). Conclusions: The eosinophilic COPD phenotype seems to show better clinical responses to long-term NIV than patients without this trait. Further mechanistic studies are warranted to analyse this association.<\/jats:p>","DOI":"10.3390\/biom15121728","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:30:17Z","timestamp":1765528217000},"page":"1728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Association Between the Eosinophilic COPD Phenotype with Overall Survival and Exacerbations in Patients on Long-Term Non-Invasive Ventilation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-740X","authenticated-orcid":false,"given":"Andras","family":"Bikov","sequence":"first","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PT, UK"},{"name":"Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-1219","authenticated-orcid":false,"given":"Balazs","family":"Csoma","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PT, UK"},{"name":"Department of Pulmonology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chai","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonor","family":"Croft","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bentley","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PT, UK"},{"name":"Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15076","DOI":"10.1038\/nrdp.2015.76","article-title":"Chronic obstructive pulmonary disease","volume":"1","author":"Barnes","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1152\/japplphysiol.00085.2009","article-title":"Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity","volume":"106","author":"Drakulovic","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.healun.2011.11.020","article-title":"Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease","volume":"31","author":"Andersen","year":"2012","journal-title":"J. Heart Lung Transplant. Off. Publ. Int. Soc. Heart Transplant."},{"key":"ref_4","first-page":"2178","article-title":"Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage","volume":"24","author":"Wang","year":"2010","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1465-9921-15-30","article-title":"Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: A population-based prospective study","volume":"15","author":"Ahmadi","year":"2014","journal-title":"Respir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Csoma, B., Vulpi, M.R., Dragonieri, S., Bentley, A., Felton, T., L\u00e1z\u00e1r, Z., and Bikov, A. (2022). Hypercapnia in COPD: Causes, Consequences, and Therapy. J. Clin. Med., 11.","DOI":"10.3390\/jcm11113180"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1001\/jama.2017.4451","article-title":"Effect of Home Noninvasive Ventilation with Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial","volume":"317","author":"Murphy","year":"2017","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/S2213-2600(14)70153-5","article-title":"Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: A prospective, multicentre, randomised, controlled clinical trial","volume":"2","author":"Windisch","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1136\/thx.2008.108274","article-title":"Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: A randomised controlled trial","volume":"64","author":"McEvoy","year":"2009","journal-title":"Thorax"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/jleuko\/qiae153","article-title":"The relevance of eosinophils in chronic obstructive pulmonary disease: Inflammation, microbiome, and clinical outcomes","volume":"116","author":"Higham","year":"2024","journal-title":"J. Leukoc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sivapalan, P., Bikov, A., and Jensen, J.U. (2021). Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020236"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.2147\/COPD.S100338","article-title":"Peripheral blood eosinophils: A surrogate marker for airway eosinophilia in stable COPD","volume":"11","author":"Negewo","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S2213-2600(16)00100-4","article-title":"Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial","volume":"4","author":"Watz","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1136\/thoraxjnl-2015-207021","article-title":"Blood eosinophils and inhaled corticosteroid\/long-acting \u03b2-2 agonist efficacy in COPD","volume":"71","author":"Pavord","year":"2016","journal-title":"Thorax"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1164\/rccm.201509-1869OC","article-title":"Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study","volume":"193","author":"Nielsen","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S2213-2600(18)30006-7","article-title":"Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: A post-hoc analysis of three randomised trials","volume":"6","author":"Bafadhel","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agust\u00ed, A., Edwards, L.D., Rennard, S.I., MacNee, W., Tal-Singer, R., Miller, B.E., Vestbo, J., Lomas, D.A., Calverley, P.M., and Wouters, E. (2012). Persistent systemic inflammation is associated with poor clinical outcomes in COPD: A novel phenotype. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037483"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1701162","DOI":"10.1183\/13993003.01162-2017","article-title":"Prevalence of persistent blood eosinophilia: Relation to outcomes in patients with COPD","volume":"50","author":"Casanova","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2147\/COPD.S265275","article-title":"Peripheral Blood Eosinophils and Nine Years Mortality in COPD Patients","volume":"16","author":"Prudente","year":"2021","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.2147\/COPD.S129787","article-title":"Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD","volume":"12","author":"Zysman","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.2147\/COPD.S179734","article-title":"Blood eosinophil count as a prognostic biomarker in COPD","volume":"13","author":"Oh","year":"2018","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1164\/rccm.202009-3448OC","article-title":"Inflammatory Endotype-associated Airway Microbiome in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations: A Multicohort Longitudinal Analysis","volume":"203","author":"Wang","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1177\/1535370214542072","article-title":"Effects of hypercapnia on T cells in lung ischemia\/reperfusion injury after lung transplantation","volume":"239","author":"Gao","year":"2014","journal-title":"Exp. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/aje\/kwq433","article-title":"Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries","volume":"173","author":"Quan","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S2213-2600(17)30432-0","article-title":"Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: An analysis of the SPIROMICS cohort","volume":"5","author":"Hastie","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2000838","DOI":"10.1183\/13993003.00838-2020","article-title":"High eosinophil counts predict decline in FEV(1): Results from the CanCOLD study","volume":"57","author":"Tan","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.2147\/COPD.S242809","article-title":"FEV(1) is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease","volume":"15","author":"Bikov","year":"2020","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1056\/NEJMoa0909883","article-title":"Susceptibility to exacerbation in chronic obstructive pulmonary disease","volume":"363","author":"Hurst","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1136\/thx.2005.040527","article-title":"Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease","volume":"60","author":"Salcedo","year":"2005","journal-title":"Thorax"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1164\/rccm.201201-0034OC","article-title":"Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease","volume":"186","author":"Divo","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1056\/NEJMoa021322","article-title":"The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease","volume":"350","author":"Celli","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chai, A., Csoma, B., Lazar, Z., Bentley, A., and Bikov, A. (2024). The Effect of Opioids and Benzodiazepines on Exacerbation Rate and Overall Survival in Patients with Chronic Obstructive Pulmonary Disease on Long-Term Non-Invasive Ventilation. J. Clin. Med., 13.","DOI":"10.3390\/jcm13185624"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S2213-2600(16)30148-5","article-title":"Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: A patient-level meta-analysis","volume":"4","author":"Pavord","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1136\/thoraxjnl-2012-202103","article-title":"The DECAF Score: Predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease","volume":"67","author":"Steer","year":"2012","journal-title":"Thorax"},{"key":"ref_35","first-page":"1837","article-title":"Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?","volume":"10","author":"Karakurt","year":"2015","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12931-017-0570-5","article-title":"Blood and sputum eosinophils in COPD; relationship with bacterial load","volume":"18","author":"Kolsum","year":"2017","journal-title":"Respir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1164\/rccm.201701-0009LE","article-title":"Stability of Blood Eosinophils in Patients with Chronic Obstructive Pulmonary Disease and in Control Subjects, and the Impact of Sex, Age, Smoking, and Baseline Counts","volume":"195","author":"Oshagbemi","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.alit.2022.11.012","article-title":"Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma","volume":"72","author":"Abe","year":"2023","journal-title":"Allergol. Int. Off. J. Jpn. Soc. Allergol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/bjh.14488","article-title":"Guideline for the investigation and management of eosinophilia","volume":"176","author":"Butt","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kang, H.S., Kim, S.K., Kim, Y.H., Kim, J.W., Lee, S.H., Yoon, H.K., and Rhee, C.K. (2021). The association between eosinophilic exacerbation and eosinophilic levels in stable COPD. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01443-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"00543","DOI":"10.1183\/23120541.00543-2020","article-title":"Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses","volume":"7","author":"Csoma","year":"2021","journal-title":"ERJ Open Res."},{"key":"ref_42","first-page":"354","article-title":"Blood eosinophils as predictor of outcomes in patients hospitalized for COPD exacerbations: A prospective observational study","volume":"26","author":"Kostikas","year":"2021","journal-title":"Biomark. Biochem. Indic. Expo. Response Susceptibility Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/resp.13660","article-title":"Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations","volume":"25","author":"Ko","year":"2020","journal-title":"Respirology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1164\/rccm.201911-2207OC","article-title":"Reduction in All-Cause Mortality with Fluticasone Furoate\/Umeclidinium\/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease","volume":"201","author":"Lipson","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1056\/NEJMoa1916046","article-title":"Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD","volume":"383","author":"Rabe","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S2213-2600(19)30190-0","article-title":"Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: Analysis of the IMPACT trial","volume":"7","author":"Pascoe","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12931-021-01777-x","article-title":"Triple versus LAMA\/LABA combination therapy for patients with COPD: A systematic review and meta-analysis","volume":"22","author":"Koarai","year":"2021","journal-title":"Respir. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1378\/chest.06-2124","article-title":"Predictors of survival in COPD patients with chronic hypercapnic respiratory failure receiving noninvasive home ventilation","volume":"131","author":"Budweiser","year":"2007","journal-title":"Chest"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1164\/rccm.202306-1060OC","article-title":"Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease","volume":"210","author":"Meldrum","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:55:47Z","timestamp":1765529747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":49,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["biom15121728"],"URL":"https:\/\/doi.org\/10.3390\/biom15121728","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}