{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:36:51Z","timestamp":1780418211646,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Boehriner Ingelheim GmbH, Switzerland"},{"name":"GSK AG Switzerland"},{"name":"Novartis AG Switzerland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. Methods: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire\u2014based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. Results: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). Conclusion: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.<\/jats:p>","DOI":"10.3390\/jcm12206695","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T10:32:24Z","timestamp":1698057144000},"page":"6695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort"],"prefix":"10.3390","volume":"12","author":[{"given":"Nebal S.","family":"Abu Hussein","sequence":"first","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"},{"name":"Department of Pulmonary Medicine, Inselspital, Bern University Hospital, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, University of Bern, 3012 Bern, Switzerland"},{"name":"Pulmonary, Critical Care & Sleep Medicine, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Giezendanner","sequence":"additional","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Urwyler","sequence":"additional","affiliation":[{"name":"University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8021-0950","authenticated-orcid":false,"given":"Pierre-Olivier","family":"Bridevaux","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, H\u00f4pital du Valais, 1950 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant N.","family":"Chhajed","sequence":"additional","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Geiser","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Inselspital, Bern University Hospital, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladina","family":"Joos Zellweger","sequence":"additional","affiliation":[{"name":"St. Claraspital, 4058 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Kohler","sequence":"additional","affiliation":[{"name":"University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Miedinger","sequence":"additional","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Pasha","sequence":"additional","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Thurnheer","sequence":"additional","affiliation":[{"name":"Kantonsspital Muensterlingen, 8596 M\u00fcnsterlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"von Garnier","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Medicine, CHUV, University Hospital Lausanne, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5554-0675","authenticated-orcid":false,"given":"Joerg D.","family":"Leuppi","sequence":"additional","affiliation":[{"name":"University Institute of Internal Medicine, Cantonal Hospital Baselland, 4031 Liestal, Switzerland"},{"name":"Medical Faculty, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref_1","unstructured":"(2023, January 11). World Health Organization. Available online: http:\/\/www.who.int."},{"key":"ref_2","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (2023, October 07). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease; 2021 Report. Available online: https:\/\/staging.goldcopd.org\/2021-gold-reports\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1183\/09031936.04.00014304","article-title":"Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS\/ERS position paper","volume":"23","author":"Celli","year":"2004","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1164\/rccm.200703-456SO","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary","volume":"176","author":"Rabe","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1164\/rccm.200902-0271OC","article-title":"Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: The DOSE Index","volume":"180","author":"Jones","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","first-page":"528","article-title":"APACHE II scores in the prediction of multiple organ failure syndrome","volume":"126","author":"Siro","year":"1991","journal-title":"Arch. Surg."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1016\/S2589-7500(22)00232-1","article-title":"Predicting severe chronic obstructive pulmonary disease exacerbations using quantitative CT: A retrospective model development and external validation study","volume":"5","author":"Chaudhary","year":"2023","journal-title":"Lancet Digit. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2147\/COPD.S194922","article-title":"A clinical prediction model for hospitalized COPD exacerbations based on \u201ctreatable traits\u201d","volume":"14","author":"Yii","year":"2019","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.2147\/COPD.S142378","article-title":"Prediction models for exacerbations in different COPD patient populations: Comparing results of five large data sources","volume":"12","author":"Hoogendoorn","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101574","DOI":"10.1016\/j.eclinm.2022.101574","article-title":"ACCEPT 2.0: Recalibrating and externally validating the Acute COPD exacerbation prediction tool (ACCEPT)","volume":"51","author":"Safari","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_12","first-page":"w13053","article-title":"General practitioner\u2019s adherence to the COPD GOLD guidelines: Baseline data of the Swiss COPD Cohort Study","volume":"140","author":"Jochmann","year":"2010","journal-title":"Swiss Med. Wkly."},{"key":"ref_13","first-page":"w13567","article-title":"Impact of adherence to the GOLD guidelines on symptom prevalence, lung function decline and exacerbation rate in the Swiss COPD cohort","volume":"142","author":"Jochmann","year":"2012","journal-title":"Swiss Med. Wkly."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2101499","DOI":"10.1183\/13993003.01499-2021","article-title":"ERS\/ATS technical standard on interpretive strategies for routine lung function tests","volume":"60","author":"Stanojevic","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000363770","article-title":"The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts","volume":"88","author":"Schoenenberger","year":"2014","journal-title":"Respiration"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1164\/rccm.201204-0596PP","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary","volume":"187","author":"Vestbo","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1183\/09031936.00102509","article-title":"Development and first validation of the COPD Assessment Test","volume":"34","author":"Jones","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_18","first-page":"577","article-title":"The clinical diagnosis of pulmonary emphysema; an experimental study","volume":"45","author":"Fletcher","year":"1952","journal-title":"Proc. R. Soc. Med."},{"key":"ref_19","unstructured":"Team, R.C., and R: A Language and Environment for Statistical Computing (2021, September 15). R Foundation for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nelson, W.B. (2003). Recurrent Events Data Analysis for Product Repairs, Disease Recurrences, and Other Applications, SIAM.","DOI":"10.1137\/1.9780898718454"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/00401706.1995.10484300","article-title":"Some simple robust methods for the analysis of recurrent events","volume":"37","author":"Lawless","year":"1995","journal-title":"Technometrics"},{"key":"ref_22","first-page":"147","article-title":"Confidence limits for recurrence data\u2014Applied to cost or number of product repairs","volume":"37","author":"Nelson","year":"1995","journal-title":"Technometrics"},{"key":"ref_23","unstructured":"Chiou, S.H., Xu, G., Yan, J., and Huang, C.-Y. (2021). Regression Modeling for Recurrent Events Using R Package reReg. arXiv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.rmed.2011.09.010","article-title":"Barriers to adherence to COPD guidelines among primary care providers","volume":"106","author":"Perez","year":"2012","journal-title":"Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2147\/COPD.S27887","article-title":"Guideline-based survey of outpatient COPD management by pulmonary specialists in Germany","volume":"7","author":"Glaab","year":"2012","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1378\/chest.14-0655","article-title":"Hospitalized exacerbations of COPD: Risk factors and outcomes in the ECLIPSE cohort","volume":"147","author":"Maselli","year":"2015","journal-title":"Chest"},{"key":"ref_27","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":"Sanchez","year":"2005","journal-title":"Thorax"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/fampra\/cmt055","article-title":"Predictors of exacerbations of asthma and COPD during one year in primary care","volume":"30","author":"Spigt","year":"2013","journal-title":"Fam. Pr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4104\/pcrj.2013.00087","article-title":"Management of COPD exacerbations in primary care: A clinical cohort study","volume":"22","author":"Sundh","year":"2013","journal-title":"Prim. Care Respir. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1378\/chest.115.3.635","article-title":"Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD","volume":"115","author":"Friedman","year":"1999","journal-title":"Chest"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1801261","DOI":"10.1183\/13993003.01261-2018","article-title":"What is a COPD exacerbation? Current definitions, pitfalls, challenges and opportunities for improvement","volume":"52","author":"Kim","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Marshall, D.C., Al Omari, O., Goodall, R., Shalhoub, J., Adcock, I.M., Chung, K.F., and Salciccioli, J.D. (2022). Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: An observational study of the global burden of disease database, 2001\u20132019. BMC Pulm. Med., 22.","DOI":"10.1186\/s12890-022-02074-z"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s10198-019-01119-1","article-title":"The economic burden of chronic obstructive pulmonary disease (COPD) in Europe: Results from a systematic review of the literature","volume":"21","author":"Rehman","year":"2020","journal-title":"Eur. J. Health Econ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1164\/rccm.200310-1443OC","article-title":"Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease","volume":"169","author":"Wilkinson","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1200\/JCO.2016.69.2467","article-title":"Lung Cancer Risk Prediction Model Incorporating Lung Function: Development and Validation in the UK Biobank Prospective Cohort Study","volume":"35","author":"Muller","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1055\/s-0037-1613830","article-title":"Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED D-dimer","volume":"83","author":"Wells","year":"2000","journal-title":"Thromb. Haemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1378\/chest.129.4.835","article-title":"Change in the BODE index reflects disease modification in COPD: Lessons from lung volume reduction surgery","volume":"129","author":"Celli","year":"2006","journal-title":"Chest"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kate, R.J., Pearce, N., Mazumdar, D., and Nilakantan, V. (2020). A continual prediction model for inpatient acute kidney injury. Comput. Biol. Med., 116.","DOI":"10.1016\/j.compbiomed.2019.103580"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S2213-2600(19)30397-2","article-title":"The Acute COPD Exacerbation Prediction Tool (ACCEPT): A modelling study","volume":"8","author":"Adibi","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2147\/COPD.S49609","article-title":"Development and validation of a model to predict the risk of exacerbations in chronic obstructive pulmonary disease","volume":"8","author":"Bertens","year":"2013","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1378\/chest.11-0281","article-title":"Influence of season on exacerbation characteristics in patients with COPD","volume":"141","author":"Donaldson","year":"2012","journal-title":"Chest"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1378\/chest.09-2029","article-title":"Increased risk of myocardial infarction and stroke following exacerbation of COPD","volume":"137","author":"Donaldson","year":"2010","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0140-6736(09)61301-5","article-title":"Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: The updated BODE index and the ADO index","volume":"374","author":"Puhan","year":"2009","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e002152","DOI":"10.1136\/bmjopen-2012-002152","article-title":"Large-scale international validation of the ADO index in subjects with COPD: An individual subject data analysis of 10 cohorts","volume":"2","author":"Puhan","year":"2012","journal-title":"BMJ Open"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6695\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:19Z","timestamp":1760130619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["jcm12206695"],"URL":"https:\/\/doi.org\/10.3390\/jcm12206695","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}