{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:05:59Z","timestamp":1789679159059,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"publisher","award":["106\/2012"],"award-info":[{"award-number":["106\/2012"]}],"id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sociedad Valenciana Neumolog\u00eda","award":["2017\/0694"],"award-info":[{"award-number":["2017\/0694"]}]},{"DOI":"10.13039\/501100014337","name":"Menarini Group","doi-asserted-by":"publisher","award":["2011\/0342"],"award-info":[{"award-number":["2011\/0342"]}],"id":[{"id":"10.13039\/501100014337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1\u03b2, IL-6, IL 8; tumor necrosis factor-alpha (\u03b1)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1\u03b2, IL-8, and tumor necrosis factor-\u03b1 levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.<\/jats:p>","DOI":"10.3390\/jcm9082631","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T09:23:44Z","timestamp":1597310624000},"page":"2631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"9","author":[{"given":"Rosario","family":"Men\u00e9ndez","sequence":"first","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"},{"name":"CIBER Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-9836","authenticated-orcid":false,"given":"Ra\u00fal","family":"M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Amara-Elori","sequence":"additional","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Reyes","sequence":"additional","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Montull","sequence":"additional","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Feced","sequence":"additional","affiliation":[{"name":"Pulmonary Medicine Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Alonso","sequence":"additional","affiliation":[{"name":"Laboratory Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46023 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanel","family":"Amaro","sequence":"additional","affiliation":[{"name":"CIBER Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"},{"name":"Pulmonary Medicine Department, Hospital Cl\u00ednico y Provincial, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6036-9545","authenticated-orcid":false,"given":"Victoria","family":"Alcaraz","sequence":"additional","affiliation":[{"name":"CIBER Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"},{"name":"Pulmonary Medicine Department, Hospital Cl\u00ednico y Provincial, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-9636","authenticated-orcid":false,"given":"Laia","family":"Fernandez-Barat","sequence":"additional","affiliation":[{"name":"CIBER Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"},{"name":"Pulmonary Medicine Department, Hospital Cl\u00ednico y Provincial, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-2167","authenticated-orcid":false,"given":"Antoni","family":"Torres","sequence":"additional","affiliation":[{"name":"CIBER Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"},{"name":"Pulmonary Medicine Department, Hospital Cl\u00ednico y Provincial, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1164\/rccm.201303-0411CI","article-title":"Non-cystic fibrosis bronchiectasis","volume":"188","author":"McShane","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1183\/09031936.00119114","article-title":"Management of bronchiectasis in adults","volume":"45","author":"Chalmers","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_3","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_4","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_5","first-page":"1602","article-title":"A comprehensive analysis of the impact of pseudomonas aeruginosa colonisation on prognosis in adult bronchiectasis","volume":"12","author":"Finch","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Men\u00e9ndez, R., M\u00e9ndez, R., Polverino, E., Rosales-Mayor, E., Amara-Elori, I., Reyes, S., Sahuquillo-Arce, J.M., Fernandez-Barat, L., Alcaraz, V., and Torres, A. (2017). Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2754-5"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1378\/chest.07-0490","article-title":"Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis","volume":"132","author":"Soriano","year":"2007","journal-title":"Chest"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1183\/13993003.01033-2015","article-title":"Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: A population-based cohort study","volume":"47","author":"Quint","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1378\/chest.10-0099","article-title":"Trends and burden of bronchiectasis-associated hospitalizations in the United States, 1993\u20132006","volume":"138","author":"Seitz","year":"2010","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.rmed.2017.04.009","article-title":"The heterogeneity of systemic inflammation in bronchiectasis","volume":"127","author":"Saleh","year":"2017","journal-title":"Respir. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S0140-6736(18)31767-7","article-title":"Advances in bronchiectasis: Endotyping, genetics, microbiome, and disease heterogeneity","volume":"392","author":"Flume","year":"2018","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201203-0487OC","article-title":"Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis","volume":"186","author":"Chalmers","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.4187\/respcare.04004","article-title":"Inflammatory responses, spirometry, and quality of life in subjects with bronchiectasis exacerbations","volume":"60","author":"Guan","year":"2015","journal-title":"Respir. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-pathol-012615-044344","article-title":"Bronchiectasis: Current concepts in pathogenesis, immunology, and microbiology","volume":"11","author":"Boyton","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, A.C.H., Martin, M.L., Lourie, R., Rogers, G.B., Burr, L.D., Hasnaim, S.Z., Bowler, S.D., McGuckin, M.A., and Serisier, D. (2015). Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119325"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1157\/13128330","article-title":"Diagnosis and treatment of bronchiectasis. Spanish society of pneumology and thoracic surgery","volume":"44","author":"Vendrell","year":"2008","journal-title":"Arch. Bronconeumol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jinf.2015.03.009","article-title":"Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients","volume":"71","author":"Polverino","year":"2015","journal-title":"J. Infect."},{"key":"ref_18","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":"Maiz","year":"2018","journal-title":"Arch. Bronconeumol."},{"key":"ref_19","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_20","unstructured":"Hosmer, D.W., and Lemeshow, S. (1989). Applied Logistic Regression, John Wiley."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1136\/thoraxjnl-2015-208188","article-title":"Bronchiectasis and the risk of cardiovascular disease: A population-based study","volume":"72","author":"Navaratnam","year":"2017","journal-title":"Thorax"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1701121","DOI":"10.1183\/13993003.01127-2017","article-title":"Correlates and assessment of excess cardiovascular risk in bronchiectasis","volume":"50","author":"Saleh","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1177\/1479972308091823","article-title":"Quality of life and inflammation in exacerbations of bronchiectasis","volume":"5","author":"Courtney","year":"2008","journal-title":"Chronic Respir. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"L6","DOI":"10.1152\/ajplung.00344.2017","article-title":"IL-17 in the lung: The good, the bad, and the ugly","volume":"314","author":"Gurczynski","year":"2017","journal-title":"Am. J. Phys. Lung Cell. Mol. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.it.2017.01.006","article-title":"IL-17 Signaling: The yin and the yang","volume":"38","author":"Amatya","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ritchie, N.D., Ritchie, R., Bayes, H.K., Mitchell, T.J., and Evans, T.J. (2018). IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007099"},{"key":"ref_27","first-page":"1","article-title":"IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa","volume":"6","author":"Cigana","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00408-014-9619-0","article-title":"Low-dose clarithromycin therapy modulates Th17 response in non-cystic fibrosis bronchiectasis patients","volume":"192","author":"Fouka","year":"2014","journal-title":"Lung"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12931-015-0167-9","article-title":"Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: A prospective observational cohort study","volume":"16","author":"Brill","year":"2015","journal-title":"Respir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1164\/rccm.201809-1651OC","article-title":"Airway bacterial load and inhaled antibiotic response in bronchiectasis","volume":"200","author":"Sibila","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","first-page":"14","article-title":"Clinical fingerprinting: A way to address the complexity and heterogeneity of bronchiectasis in practice","volume":"201","author":"Aksamit","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/8\/2631\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:00:17Z","timestamp":1760176817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/8\/2631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,13]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["jcm9082631"],"URL":"https:\/\/doi.org\/10.3390\/jcm9082631","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,13]]}}}