{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:58:13Z","timestamp":1788865093291,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>We evaluated whether the pathogens identified during acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) are associated with the COPD medications used in the 6 months before AE-COPD. We collected the medical records of patients diagnosed with AE-COPD at 28 hospitals between January 2008 and December 2019 and retrospectively analyzed them. Microorganisms identified at the time of AE-COPD were analyzed according to the use of inhaled corticosteroid (ICS) and systemic steroid after adjusting for COPD severity. We evaluated 1177 patients with AE-COPD and available medication history. The mean age of the patients was 73.9 \u00b1 9.2 years, and 83% were males. The most frequently identified bacteria during AE-COPD were Pseudomonas aeruginosa (10%), followed by Mycoplasma pneumoniae (9.4%), and Streptococcus pneumoniae (5.1%), whereas the most commonly identified viruses were rhinovirus (11%) and influenza A (11%). During AE-COPD, bacteria were more frequently identified in the ICS than non-ICS group (p = 0.009), and in the systemic steroid than non-systemic steroid group (p &lt; 0.001). In patients who used systemic steroids before AE-COPD, the risk of detecting Pseudomonas aeruginosa was significantly higher during AE-COPD (OR 1.619, CI 1.007\u20132.603, p = 0.047), but ICS use did not increase the risk of Pseudomonas detection. The risk of respiratory syncytial virus (RSV) detection was low when ICS was used (OR 0.492, CI 0.244\u20130.988, p = 0.045). COPD patients who used ICS had a lower rate of RSV infection and similar rate of P. aeruginosa infection during AE-COPD compared to patients who did not use ICS. However, COPD patients who used systemic steroids within 6 months before AE-COPD had an increased risk of P. aeruginosa infection. Therefore, anti-pseudomonal antibiotics should be considered in patients with AE-COPD who have used systemic steroids.<\/jats:p>","DOI":"10.3390\/jcm12010111","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T02:50:01Z","timestamp":1672109401000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["COPD Exacerbation-Related Pathogens and Previous COPD Treatment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-4947","authenticated-orcid":false,"given":"Yun Su","family":"Sim","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul 07441, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0843-9862","authenticated-orcid":false,"given":"Jin Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eung Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Bucheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0286-2638","authenticated-orcid":false,"given":"Tai Joon","family":"An","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-1530","authenticated-orcid":false,"given":"Yeonhee","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Soon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-2657","authenticated-orcid":false,"given":"Kwang Ha","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.4046\/trd.2018.0029","article-title":"Revised (2018) COPD Clinical Practice Guideline of the Korean Academy of Tuberculosis and Respiratory Disease: A Summary","volume":"81","author":"Park","year":"2018","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1183\/09059180.00003609","article-title":"Epidemiology of COPD","volume":"18","author":"Raherison","year":"2009","journal-title":"Eur. Respir. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1056\/NEJMra0800353","article-title":"Infection in the pathogenesis and course of chronic obstructive pulmonary disease","volume":"359","author":"Sethi","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/archinte.165.8.891","article-title":"Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease","volume":"165","author":"Rosell","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.2147\/COPD.S82752","article-title":"Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods","volume":"10","author":"Shimizu","year":"2015","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4046\/trd.2021.0080","article-title":"A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea","volume":"85","author":"Lee","year":"2022","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2147\/COPD.S360222","article-title":"The Relationship between Comorbidities and Microbiologic Findings in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"17","author":"Seo","year":"2022","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1001\/archinternmed.2008.550","article-title":"Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: A meta-analysis","volume":"169","author":"Singh","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1183\/16000617.0075-2021","article-title":"Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD","volume":"30","author":"Miravitlles","year":"2021","journal-title":"Eur. Respir. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1136\/thoraxjnl-2012-201772","article-title":"Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis","volume":"68","author":"Andrejak","year":"2013","journal-title":"Thorax"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1700037","DOI":"10.1183\/13993003.00037-2017","article-title":"The risk of mycobacterial infections associated with inhaled corticosteroid use","volume":"50","author":"Brode","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1164\/rccm.201007-1099OC","article-title":"Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases","volume":"183","author":"Brassard","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1164\/rccm.200611-1630OC","article-title":"Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia","volume":"176","author":"Ernst","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1136\/thoraxjnl-2012-203175","article-title":"Use of inhaled corticosteroids and the risk of tuberculosis","volume":"68","author":"Lee","year":"2013","journal-title":"Thorax"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1136\/thoraxjnl-2012-202872","article-title":"Inhaled corticosteroids in COPD and the risk of serious pneumonia","volume":"68","author":"Suissa","year":"2013","journal-title":"Thorax"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e001067","DOI":"10.1136\/bmjresp-2021-001067","article-title":"Inhaled corticosteroid dose is associated with Pseudomonas aeruginosa infection in severe COPD","volume":"8","author":"Shafiek","year":"2021","journal-title":"BMJ Open Respir. Res."},{"key":"ref_18","unstructured":"GOLD (2022, July 01). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung Disease. Available online: https:\/\/goldcopd.org\/wp-content\/uploads\/2019\/12\/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2147\/COPD.S30568","article-title":"Microbiological study of patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and the usefulness of analytical and clinical parameters in its identification (VIRAE study)","volume":"7","author":"Boixeda","year":"2012","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1700451","DOI":"10.1183\/13993003.00451-2017","article-title":"Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD","volume":"50","author":"Contoli","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1136\/thoraxjnl-2021-217160","article-title":"Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease","volume":"77","author":"Eklof","year":"2022","journal-title":"Thorax"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"601","DOI":"10.2147\/DDDT.S63100","article-title":"Chronic obstructive pulmonary disease treated with inhaled medium- or high-dose corticosteroids: A prospective and randomized study focusing on clinical efficacy and the risk of pneumonia","volume":"8","author":"Cheng","year":"2014","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1159\/000439226","article-title":"Budesonide Inhibits Intracellular Infection with Non-Typeable Haemophilus influenzae Despite Its Anti-Inflammatory Effects in Respiratory Cells and Human Lung Tissue: A Role for p38 MAP Kinase","volume":"90","author":"Wagner","year":"2015","journal-title":"Respiration"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1183\/09031936.00003309","article-title":"Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: A prospective study","volume":"34","author":"Almagro","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5152\/TurkThoracJ.2017.17035","article-title":"A Prospective Study of Bacteriological Etiology in Hospitalized Acute Exacerbation of COPD Patients: Relationship with Lung Function and Respiratory Failure","volume":"19","author":"Kuwal","year":"2018","journal-title":"Turk. Thorac. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.4049\/jimmunol.1302138","article-title":"Chronic exposure to glucocorticoids shapes gene expression and modulates innate and adaptive activation pathways in macrophages with distinct changes in leukocyte attraction","volume":"192","author":"Martinez","year":"2014","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s15010-015-0833-3","article-title":"Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease","volume":"44","author":"Sethi","year":"2016","journal-title":"Infection"},{"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":"227","DOI":"10.1016\/j.cmi.2019.06.011","article-title":"Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: An observational cohort study of 22,053 patients","volume":"26","author":"Eklof","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1183\/09031936.00073506","article-title":"The role of nebulised budesonide in the treatment of exacerbations of COPD","volume":"29","author":"Gunen","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1183\/09031936.00012707","article-title":"The role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease","volume":"30","author":"Diederen","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.medmal.2016.12.002","article-title":"Prevalence of Chlamydophila pneumoniae and Mycoplasma pneumoniae IgM and IgG antibodies in Tunisian patients presenting with exacerbation of chronic obstructive pulmonary disease","volume":"47","author":"Messous","year":"2017","journal-title":"Med. Mal. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/crj.13286","article-title":"The role of typical and atypical pathogens in acute exacerbations of chronic obstructive pulmonary disease","volume":"15","author":"Yildiz","year":"2021","journal-title":"Clin. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1099\/jmm.0.003335-0","article-title":"Role of Mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease","volume":"58","author":"Dwivedi","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3904\/kjim.2017.279","article-title":"Use of serology and polymerase chain reaction to detect atypical respiratory pathogens during acute exacerbation of chronic obstructive pulmonary disease","volume":"33","author":"Jung","year":"2018","journal-title":"Korean J. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/infdis\/139.6.681","article-title":"Long-term epidemiology of infections with Mycoplasma pneumoniae","volume":"139","author":"Foy","year":"1979","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1086\/592281","article-title":"Community outbreak of Mycoplasma pneumoniae infection: School-based cluster of neurologic disease associated with household transmission of respiratory illness","volume":"198","author":"Walter","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1378\/chest.07-0530","article-title":"Viral etiology of acute exacerbations of COPD in Hong Kong","volume":"132","author":"Ko","year":"2007","journal-title":"Chest"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0002-9343(03)00353-X","article-title":"Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease","volume":"115","author":"Tan","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/imj.13213","article-title":"Viruses are frequently present as the infecting agent in acute exacerbations of chronic obstructive pulmonary disease in patients presenting to hospital","volume":"46","author":"Biancardi","year":"2016","journal-title":"Intern. Med. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Love, M.E., and Proud, D. (2022). Respiratory Viral and Bacterial Exacerbations of COPD-The Role of the Airway Epithelium. Cells, 11.","DOI":"10.3390\/cells11091416"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.resinv.2021.08.009","article-title":"Differences in the spectrum of respiratory viruses and detection of human rhinovirus C in exacerbations of adult asthma and chronic obstructive pulmonary disease","volume":"60","author":"Kan","year":"2022","journal-title":"Respir. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/0970-2113.197099","article-title":"Respiratory viruses in acute exacerbations of chronic obstructive pulmonary disease","volume":"34","author":"Koul","year":"2017","journal-title":"Lung India"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1002\/jmv.24577","article-title":"Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia","volume":"88","author":"Kim","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.2147\/COPD.S306916","article-title":"Incidence and Prognostic Factors of Respiratory Viral Infections in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"16","author":"Jang","year":"2021","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7176","DOI":"10.1038\/srep07176","article-title":"Glucocorticosteroids enhance replication of respiratory viruses: Effect of adjuvant interferon","volume":"4","author":"Thomas","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.resinv.2014.03.004","article-title":"Formoterol and budesonide inhibit rhinovirus infection and cytokine production in primary cultures of human tracheal epithelial cells","volume":"52","author":"Yamaya","year":"2014","journal-title":"Respir. Investig."},{"key":"ref_48","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."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:10Z","timestamp":1760147350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,23]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["jcm12010111"],"URL":"https:\/\/doi.org\/10.3390\/jcm12010111","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,23]]}}}