{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:20:46Z","timestamp":1790886046881,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 18\/00075"],"award-info":[{"award-number":["FIS 18\/00075"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI 21\/00215"],"award-info":[{"award-number":["PI 21\/00215"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann\u2013Whitney U test and eosinophil count threshold: 100 cells\/\u00b5L) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.<\/jats:p>","DOI":"10.3390\/ijerph18168431","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T08:57:14Z","timestamp":1628585834000},"page":"8431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity"],"prefix":"10.3390","volume":"18","author":[{"given":"Xuejie","family":"Wang","sequence":"first","affiliation":[{"name":"Lung Cancer and Muscle Research Group, Pulmonology Department, Hospital del Mar-IMIM, Parc de Salut Mar, 08003 Barcelona, Spain"},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Villa","sequence":"additional","affiliation":[{"name":"Respiratory Department, Cl\u00ednica Fuensanta, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadira","family":"Dobarganes","sequence":"additional","affiliation":[{"name":"Respiratory Department, Cl\u00ednica Fuensanta, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-7400","authenticated-orcid":false,"given":"Casilda","family":"Olveira","sequence":"additional","affiliation":[{"name":"Respiratory Department, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Hospital Regional Universitario de M\u00e1laga, Universidad de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Gir\u00f3n","sequence":"additional","affiliation":[{"name":"Respiratory Department, Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de la Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garc\u00eda-Clemente","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"M\u00e1iz","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Ramon y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Sibila","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3759-5322","authenticated-orcid":false,"given":"Rafael","family":"Golpe","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Lucus Augusti, 27003 Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-9768","authenticated-orcid":false,"given":"Juan","family":"Rodr\u00edguez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital San Agustin, Avil\u00e9s, 33401 Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Prados","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital la Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-1891","authenticated-orcid":false,"given":"Miguel Angel","family":"Martinez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Respiratory Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-2484","authenticated-orcid":false,"given":"Juan Luis","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Respiratory Department, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"},{"name":"Departament of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0753-1771","authenticated-orcid":false,"given":"David","family":"de la Rosa","sequence":"additional","affiliation":[{"name":"Respiratory Department, Hospital Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Duran","sequence":"additional","affiliation":[{"name":"Scientific and Technical Department, Hospital del Mar-IMIM, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-7520","authenticated-orcid":false,"given":"Jordi","family":"Garcia-Ojalvo","sequence":"additional","affiliation":[{"name":"Department of Health and Experimental Sciences (CEXS), Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Lung Cancer and Muscle Research Group, Pulmonology Department, Hospital del Mar-IMIM, Parc de Salut Mar, 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"},{"name":"Department of Health and Experimental Sciences (CEXS), Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.arbres.2018.09.010","article-title":"Heterogeneidad y complejidad del s\u00edndrome bronquiectasias: Un reto pendiente","volume":"55","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.arbres.2019.05.001","article-title":"Bronquiectasias: Cuando la evidencia cient\u00edfica publicada no resulta suficiente","volume":"55","author":"Olveira","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.arbr.2019.06.004","article-title":"Bronchiectasis: A Complex, Heterogeneous Disease","volume":"55","author":"Olveira","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Men\u00e9ndez, R., M\u00e9ndez, R., Amara-Elori, I., Reyes, S., Montull, B., Feced, L., Alonso, R., Amaro, R., Alcaraz, V., and Fernandez-Barat, L. (2020). Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082631"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1700051","DOI":"10.1183\/13993003.00051-2017","article-title":"Pulmonary exacerbation in adults with bronchiectasis: A consensus definition for clinical research","volume":"49","author":"Hill","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e000348","DOI":"10.1136\/bmjresp-2018-000348","article-title":"British Thoracic Society guideline for bronchiectasis in adults","volume":"5","author":"Hill","year":"2018","journal-title":"BMJ Open Respir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.arbr.2017.07.013","article-title":"Spanish Guidelines on the Evaluation and Diagnosis of Bronchiectasis in Adults","volume":"54","author":"Olveira","year":"2018","journal-title":"Arch. Bronconeumol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.arbr.2017.07.014","article-title":"Spanish Guidelines on Treatment of Bronchiectasis in Adults","volume":"54","author":"Olveira","year":"2018","journal-title":"Arch. Bronconeumol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1164\/rccm.201711-2202OC","article-title":"Characterization of the \u201cfrequent exacerbator phenotype\u201d in bronchiectasis","volume":"197","author":"Chalmers","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-018-0042-3","article-title":"Bronchiectasis","volume":"4","author":"Chalmers","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.4187\/respcare.05276","article-title":"Serum albumin and disease severity of non-cystic fibrosis bronchiectasis","volume":"62","author":"Lee","year":"2018","journal-title":"Respir. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1183\/09031936.98.12040820","article-title":"Systemic markers of inflammation in stable bronchiectasis","volume":"12","author":"Wilson","year":"1998","journal-title":"Eur. Respir J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1365-2249.2006.03091.x","article-title":"Assessing immune function in adult bronchiectasis","volume":"144","author":"King","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1046\/j.1365-2249.2002.01974.x","article-title":"Humoral immunity and bronchiectasis","volume":"130","author":"Stead","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1128\/iai.61.7.2848-2853.1993","article-title":"Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro","volume":"61","author":"Kanthakumar","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1183\/09031936.00069007","article-title":"Mucosal inflammation in idiopathic bronchiectasis: Cellular and molecular mechanisms","volume":"31","author":"Fuschillo","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2000453","DOI":"10.1183\/13993003.00453-2020","article-title":"Blood eosinophils predict inhaled fluticasone response in bronchiectasis","volume":"56","author":"Aliberti","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2002005","DOI":"10.1183\/13993003.02005-2020","article-title":"Blood eosinophils do not predict inhaled budesonide response in bronchiectasis","volume":"56","author":"Lipworth","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_19","first-page":"681","article-title":"Repeteability of Circulating Eosinophil Measures and Inhaled Corticosteroids Effect in Bronchiectasis. A Post Hoc Analysis of a Randomized Clinical Trial","volume":"56","author":"Posadas","year":"2020","journal-title":"Arch. Bronconeumol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1901333","DOI":"10.1183\/13993003.01333-2019","article-title":"Anti-IL5 and anti-IL5R\u03b1 therapy for clinically significant bronchiectasis with eosinophilic endotype: A case series","volume":"55","author":"Rademacher","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/JAA.S196200","article-title":"Severe uncontrolled asthma with bronchiectasis: A pilot study of an emerging phenotype that responds to mepolizumab","volume":"12","author":"Carpagnano","year":"2019","journal-title":"J. Asthma Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106127","DOI":"10.1016\/j.rmed.2020.106127","article-title":"Role of inhaled corticosteroids in reducing exacerbations in bronchiectasis patients with blood eosinophilia pooled post-hoc analysis of 2 randomized clinical trials","volume":"172","author":"Posadas","year":"2020","journal-title":"Respir. Med."},{"key":"ref_23","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_24","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_25","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cmi.2020.04.007","article-title":"Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis","volume":"27","author":"Oscullo","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.21037\/jtd.2017.08.53","article-title":"Distance-saturation product of the 6-min walk test predicts mortality of patients with non-cystic fibrosis bronchiectasis","volume":"9","author":"Hsieh","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/j.chest.2020.11.011","article-title":"A Cluster Analysis of Bronchiectasis Patients Based on the Airway Immune Profile","volume":"159","author":"Perea","year":"2021","journal-title":"Chest"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12931-017-0659-x","article-title":"Factors associated with hospitalization in bronchiectasis exacerbations: A one-year follow-up study","volume":"18","author":"Polverino","year":"2017","journal-title":"Respir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"BSR20194514","DOI":"10.1042\/BSR20194514","article-title":"Prognostic performance of the FACED score and bronchiectasis severity index in bronchiectasis: A systematic review and meta-analysis","volume":"40","author":"He","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.arbr.2020.11.010","article-title":"RIBRON: The spanish Online Bronchiectasis Registry. Characterization of the First 1912 Patients","volume":"57","author":"Villa","year":"2021","journal-title":"Arch. Bronconeumol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.arbres.2019.12.017","article-title":"C-Reactive Protein Concentration in Steady-State Bronchiectasis: Prognostic Value of Future Severe Exacerbations. Data From the Spanish Registry of Bronchiectasis (RIBRON)","volume":"57","author":"Posadas","year":"2021","journal-title":"Arch. Bronconeumol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1700629","DOI":"10.1183\/13993003.00629-2017","article-title":"European Respiratory Society guidelines for the management of adult bronchiectasis","volume":"50","author":"Polverino","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1183\/13993003.01888-2015","article-title":"Research priorities in bronchiectasis: A consensus statement from the EMBARC Clinical Research Collaboration","volume":"48","author":"Aliberti","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"548","DOI":"10.33314\/jnhrc.v17i4.1042","article-title":"The Declaration of Helsinki on Medical Research involving Human Subjects: A Review of Seventh Revision","volume":"17","author":"Shrestha","year":"2020","journal-title":"J. Nepal Health Res. Counc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1183\/09031936.00026313","article-title":"Multidimensional approach to non-cystic fibrosis bronchiectasis: The FACED score","volume":"43","author":"Giron","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2147\/COPD.S121943","article-title":"Predicting high risk of exacerbations in bronchiectasis: The E-FACED score","volume":"12","author":"Athanazio","year":"2017","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1164\/rccm.201309-1575OC","article-title":"The bronchiectasis severity index an international derivation and validation study","volume":"189","author":"Chalmers","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.4049\/jimmunol.142.12.4428","article-title":"Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein","volume":"142","author":"Lehrer","year":"1989","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1164\/rccm.201908-1550OC","article-title":"Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis","volume":"201","author":"Faner","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.rmed.2018.07.011","article-title":"Systemic inflammatory markers in relation to lung function in NHANES. 2007\u20132010","volume":"142","author":"Nerpin","year":"2018","journal-title":"Respir. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1164\/rccm.201712-2423OC","article-title":"Blood Neutrophils Are Reprogrammed in Bronchiectasis","volume":"198","author":"Bedi","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.3168\/jds.2017-13553","article-title":"Technical note: Serum total protein and immunoglobulin G concentrations in neonatal dairy calves over the first 10 days of age","volume":"101","author":"Wilm","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"857","DOI":"10.2147\/COPD.S238457","article-title":"Malnutrition, airflow limitation and severe emphysema are risks for exacerbation of chronic obstructive pulmonary disease in Japanese subjects: A retrospective single-center study","volume":"15","author":"Yamaya","year":"2020","journal-title":"Int. J. COPD"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLOS Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e018404","DOI":"10.1136\/bmjopen-2017-018404","article-title":"Examining patterns of multimorbidity, polypharmacy and risk of adverse drug reactions in chronic obstructive pulmonary disease: A cross-sectional UK Biobank study","volume":"8","author":"Hanlon","year":"2018","journal-title":"BMJ Open"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/16\/8431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:43:27Z","timestamp":1760165007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/16\/8431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,10]]},"references-count":46,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijerph18168431"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18168431","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,10]]}}}