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A total of 72 clinically stable COPD patients provided sputum and blood samples for 16S rRNA gene amplification and peripheral biomarkers. Beta-diversity analyses of the bronchial microbiome showed significant differences between infrequent and frequent (\u22652) exacerbators (p = 0.001). Haemophilus was underrepresented in frequent exacerbators (relative abundance [RA] 0.07 [0.003\u20130.31] vs. 0.24 [0.06\u20132.36], p = 0.02) while the presence of Pseudomonas was increased (7.70 [0.66\u201311.68] vs. 1.11 [0.37\u20132.88], p = 0.01). Eight common taxa, Prevotella, Moryella, Atopobium, Megasphaera, Parvimonas, Veillonella, Bulleidia and Selenomonas, showed significant decreases in their RAs when exacerbations required hospitalization. RAs of Haemophilus and eight common taxa were positively correlated (p &lt; 0.01). Among them, Porphyromonas, Leptotrichia and Selenomonas showed a negative correlation with blood interleukin-8 (IL-8) (p &lt; 0.01) and an equivalent correlation was found for Haemophilus parainfluenzae. Frequent exacerbations cause a decrease in the RA of Haemophilus and have a more extensive impact when hospitalization is required. The RAs of common bronchial bacteria were closely related and some of them were inversely associated with blood IL-8 levels.<\/jats:p>","DOI":"10.3390\/ijms27083416","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:01:52Z","timestamp":1775822512000},"page":"3416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bronchial and Systemic Relationships of Haemophilus in Chronic Obstructive Pulmonary Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Eduard","family":"Mons\u00f3","sequence":"first","affiliation":[{"name":"Institut d\u2019 Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), 08208 Sabadell, Spain"},{"name":"Barcelona Respiratory Network, 08009 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-8972","authenticated-orcid":false,"given":"Carme","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Barcelona Respiratory Network, 08009 Barcelona, Spain"},{"name":"Department of Respiratory Medicine, Hospital Del Mar, Hospital Del Mar Research Institute, MELIS, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, \u00c1rea de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Quero","sequence":"additional","affiliation":[{"name":"Institut d\u2019 Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), 08208 Sabadell, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, \u00c1rea de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-0916","authenticated-orcid":false,"given":"Sergi","family":"Pascual-Gu\u00e0rdia","sequence":"additional","affiliation":[{"name":"Barcelona Respiratory Network, 08009 Barcelona, Spain"},{"name":"Department of Respiratory Medicine, Hospital Del Mar, Hospital Del Mar Research Institute, MELIS, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, \u00c1rea de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-6555","authenticated-orcid":false,"given":"C\u00e9sar J\u00e9sse","family":"Enr\u00edquez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Barcelona Respiratory Network, 08009 Barcelona, Spain"},{"name":"Department of Respiratory Medicine, Hospital Del 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Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e300","DOI":"10.1016\/S2666-5247(21)00035-5","article-title":"Lung microbiome composition and bronchial epithelial gene expression in patients with COPD versus healthy individuals: A bacterial 16S rRNA gene sequencing and host transcriptomic analysis","volume":"2","author":"Ramsheh","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40168-017-0381-4","article-title":"The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease","volume":"6","author":"Pragman","year":"2018","journal-title":"Microbiome"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1136\/thoraxjnl-2015-207235","article-title":"Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers","volume":"71","author":"Einarsson","year":"2016","journal-title":"Thorax"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tangedal, S., Nielsen, R., Aanerud, M., Persson, L.J., Wiker, H.G., Bakke, P.S., Hiemstra, P.S., and Eagan, T.M. (2019). Sputum microbiota and inflammation at stable state and during exacerbations in a cohort of chronic obstructive pulmonary disease (COPD) patients. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222449"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jaci.2020.02.040","article-title":"The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease","volume":"147","author":"Dicker","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106099","DOI":"10.1016\/j.ebiom.2025.106099","article-title":"Characterisation of the gut-lung axis microbiome in clinically stable patients with chronic obstructive pulmonary disease","volume":"123","author":"Viglino","year":"2026","journal-title":"EBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1164\/rccm.201806-1135OC","article-title":"Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations","volume":"199","author":"Alotaibi","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1136\/thoraxjnl-2016-209023","article-title":"A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD","volume":"72","author":"Wilkinson","year":"2017","journal-title":"Thorax"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"00248-2018","DOI":"10.1183\/23120541.00248-2018","article-title":"Drivers of year-to-year variation in exacerbation frequency of COPD: Analysis of the AERIS cohort","volume":"5","author":"Wilkinson","year":"2019","journal-title":"ERJ Open Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"625","DOI":"10.12659\/MSM.895544","article-title":"The Association of Chronic Hepatitis C with Respiratory Microbiota Disturbance on the Basis of Decreased Haemophilus spp. Colonization","volume":"22","author":"Kosikowska","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kosikowska, U., Biernasiuk, A., Rybojad, P., \u0141o\u015b, R., and Malm, A. (2016). Haemophilus parainfluenzae as a marker of the upper respiratory tract microbiota changes under the influence of preoperative prophylaxis with or without postoperative treatment in patients with lung cancer. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0679-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/thorax.57.9.759","article-title":"Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations","volume":"57","author":"Patel","year":"2002","journal-title":"Thorax"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1183\/09031936.00126808","article-title":"Variability and effects of bronchial colonisation in patients with moderate COPD","volume":"35","author":"Marin","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Choi, Y.J., Park, H.J., Kim, C.Y., Choi, A., Cho, J.H., and Byun, M.K. (2024). Dynamic microbial changes in exacerbation of chronic obstructive pulmonary disease. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1507090"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Z., Liu, H., Wang, F., Yang, Y., Wang, X., Chen, B., Stampfli, M.R., Zhou, H., Shu, W., and Brightling, C.E. (2020). A Refined View of Airway Microbiome in Chronic Obstructive Pulmonary Disease at Species and Strain-Levels. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01758"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cos\u00edo, B.G., Jahn, A., Iglesias, A., Shafiek, H., Busquets, X., and Agust\u00ed, A. (2015). Haemophilus influenzae induces steroidresistant inflammatory responses in COPD. BMC Pulm. Med., 15.","DOI":"10.1186\/s12890-015-0155-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"00614-2020","DOI":"10.1183\/23120541.00614-2020","article-title":"Chronic infection by nontypeable Haemophilus influenzae fuels airway inflammation","volume":"7","author":"Saliu","year":"2021","journal-title":"ERJ Open Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1080\/1040841X.2020.1863330","article-title":"Non-typeable Haemophilus influenzae chronic colonization in chronic obstructive pulmonary disease (COPD)","volume":"47","author":"Short","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e0014023","DOI":"10.1128\/mbio.00140-23","article-title":"Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2","volume":"14","author":"Murphy","year":"2023","journal-title":"mBio"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Weeks, J.R., Staples, K.J., Spalluto, C.M., Watson, A., and Wilkinson, T.M.A. (2021). The Role of Non-Typeable Haemophilus influenzae Biofilms in Chronic Obstructive Pulmonary Disease. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.720742"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1183\/09031936.00195608","article-title":"Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD","volume":"34","author":"Miravitlles","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_24","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (2025, December 17). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2025 Report. Available online: https:\/\/www.goldcopd.org\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2147\/COPD.S346294","article-title":"Long-Term Risk of Mortality Associated with Isolation of Pseudomonas aeruginosa in COPD: A Systematic Review and Meta-Analysis","volume":"17","author":"Rigau","year":"2022","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s10096-013-2044-0","article-title":"Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa","volume":"33","author":"Millares","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12967-021-02788-4","article-title":"Association of exacerbation phenotype with the sputum microbiome in chronic obstructive pulmonary disease patients during the clinically stable state","volume":"19","author":"Yang","year":"2021","journal-title":"J. Transl. Med."},{"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":"50s","DOI":"10.1183\/09031936.01.00229701","article-title":"Cytokines in chronic obstructive pulmonary disease","volume":"34","author":"Chung","year":"2001","journal-title":"Eur. Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1183\/13993003.01406-2015","article-title":"Lung microbiome dynamics in COPD exacerbations","volume":"47","author":"Wang","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2147\/COPD.S78748","article-title":"Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation","volume":"10","author":"Tufvesson","year":"2015","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_32","first-page":"1862","article-title":"Characteristics of pathogenic microbes in lung microenvironment of lung cancer patients without respiratory infection","volume":"26","author":"Zhang","year":"2021","journal-title":"J. BUON"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1128\/CMR.00103-13","article-title":"Classification, identification, and clinical significance of Haemophilus and Aggregatibacter species with host specificity for humans","volume":"27","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.arbres.2018.07.026","article-title":"The BIOMEPOC Project: Personalized Biomarkers and Clinical Profiles in Chronic Obstructive Pulmonary Disease","volume":"55","author":"Gea","year":"2019","journal-title":"Arch. Bronconeumol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"398S","DOI":"10.1378\/chest.117.5_suppl_2.398S","article-title":"Toward a consensus definition for COPD exacerbations","volume":"117","year":"2000","journal-title":"Chest"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.2147\/COPD.S140231","article-title":"Clinical characteristics of chronic bronchitic, emphysematous and ACOS phenotypes in COPD patients with frequent exacerbations","volume":"12","author":"Cheng","year":"2017","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0025-6196(25)09678-8","article-title":"Microscopic and baceriologic analysis of expectorated sputum","volume":"50","author":"Murray","year":"1975","journal-title":"Mayo Clin. Proc."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Millares, L., Pascual, S., Mont\u00f3n, C., Garc\u00eda-N\u00fa\u00f1ez, M., Lalmolda, C., Faner, R., Casadevall, C., Set\u00f3, L., Capilla, S., and Moreno, A. (2019). Relationship between the respiratory microbiome and the severity of airflow limitation, history of exacerbations and circulating eosinophils in COPD patients. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-0867-x"},{"key":"ref_39","first-page":"00004","article-title":"COPD: Systemic proteomic profiles in frequent and infrequent exacerbators","volume":"10","author":"Casadevall","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.chom.2018.08.005","article-title":"Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease","volume":"24","author":"Teo","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00103-18","DOI":"10.1128\/mSphere.00103-18","article-title":"Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis","volume":"3","author":"Choo","year":"2018","journal-title":"mSphere"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1093\/bioinformatics\/btac399","article-title":"A rarefaction-without-resampling extension of PERMANOVA for testing presence-absence associations in the microbiome","volume":"38","author":"Hu","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3416\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T04:23:40Z","timestamp":1775967820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083416"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083416","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}