{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:13:42Z","timestamp":1778213622698,"version":"3.51.4"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009764","name":"Landstinget Blekinge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002784","name":"Canada Excellence Research Chairs, Government of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002784","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006310","name":"Medicinska Forskningsr\u00e5det","doi-asserted-by":"publisher","award":["2019-02081"],"award-info":[{"award-number":["2019-02081"]}],"id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Exertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing, but its prognostic significance is unknown. We evaluated the ability of abnormally high breathlessness intensity during incremental cycle exercise testing to predict all-cause, respiratory, and cardiac mortality.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Study design and methods<\/jats:title>\n<jats:p>Longitudinal cohort study of adults referred for exercise testing followed prospectively for mortality assessed using the Swedish National Causes of Death Registry. Abnormally high exertional breathlessness was defined as a breathlessness intensity response (Borg 0\u201310 scale) &gt; the upper limit of normal using published reference equations. Mortality was analyzed using multivariable Cox regression, unadjusted and adjusted for age, sex, and body mass index. A further mortality analysis was also done adjusted for select common comorbidities in addition to age, sex and body mass index.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the 13,506 people included (46% female, age 59\u00b115 years), 2,867 (21%) had abnormally high breathlessness during exercise testing. Over a median follow up of 8.0 years, 1,687 (12%) people died. No participant was lost to follow-up. Compared to those within normal predicted ranges, people with abnormally high exertional breathlessness had higher mortality from all causes (adjusted hazard ratio [aHR] 2.3, [95% confidence interval] 2.1\u20132.6), respiratory causes (aHR 5.2 [3.4\u20138.0]) and cardiac causes (aHR 3.0 [2.5\u20133.6]). Even among people with normal exercise capacity (defined as peak Watt \u226575% of predicted exercise capacity, n = 10,284) those with abnormally high exertional breathlessness were at greater risk of all-cause mortality than people with exertional breathlessness within the normal predicted range (aHR 1.5 [1.2\u20131.8]).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Among people referred for exercise testing, abnormally high exertional breathlessness, quantified using healthy reference values, independently predicted all-cause, respiratory and cardiac mortality.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0302111","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T18:40:54Z","timestamp":1734547254000},"page":"e0302111","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Abnormally high exertional breathlessness predicts mortality in people referred for incremental cycle exercise testing"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1831-9306","authenticated-orcid":true,"given":"Viktor","family":"Elmberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9831-9102","authenticated-orcid":true,"given":"Xingwu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2943-0034","authenticated-orcid":true,"given":"Thomas","family":"Lindow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristofer","family":"Hedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-7765","authenticated-orcid":true,"given":"Andrei","family":"Malinovschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-2937","authenticated-orcid":true,"given":"Hayley","family":"Lewthwaite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Brudin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"issue":"3","key":"pone.0302111.ref001","doi-asserted-by":"crossref","first-page":"1800079","DOI":"10.1183\/13993003.00079-2018","article-title":"The dyspnoea-inactivity vicious circle in COPD: development and external validation of a conceptual model","volume":"52","author":"MA Ramon","year":"2018","journal-title":"EUROPEAN RESPIRATORY JOURNAL"},{"issue":"6","key":"pone.0302111.ref002","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1183\/09031936.00036813","article-title":"Predictors of dyspnoea prevalence: results from the BOLD study","volume":"43","author":"R Gronseth","year":"2014","journal-title":"The European respiratory journal"},{"issue":"4","key":"pone.0302111.ref003","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1164\/rccm.201111-2042ST","article-title":"An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea","volume":"185","author":"MB Parshall","year":"2012","journal-title":"American journal of respiratory and critical care medicine"},{"issue":"1","key":"pone.0302111.ref004","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.2147\/COPD.S119992","article-title":"Persistent disabling breathlessness in chronic obstructive pulmonary disease","volume":"11","author":"J Sundh","year":"2016","journal-title":"International Journal of COPD"},{"issue":"3","key":"pone.0302111.ref005","doi-asserted-by":"crossref","first-page":"e0214083","DOI":"10.1371\/journal.pone.0214083","article-title":"Breathlessness and incidence of COPD, cardiac events and all-cause mortality: A 44-year follow-up from middle age throughout life.","volume":"14","author":"J Sandberg","year":"2019","journal-title":"PLoS One."},{"issue":"5","key":"pone.0302111.ref006","first-page":"e39192","article-title":"Breathlessness Predicts Mortality in Adults: A Systematic Review and Meta-Analysis.","volume":"15","author":"DK Sethi","year":"2023","journal-title":"Cureus"},{"issue":"7","key":"pone.0302111.ref007","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/thx.54.7.581","article-title":"Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease.","volume":"54","author":"JC Bestall","year":"1999","journal-title":"Thorax."},{"key":"pone.0302111.ref008","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.2147\/COPD.S277523","article-title":"How to Assess Breathlessness in Chronic Obstructive Pulmonary Disease.","volume":"16","author":"H Lewthwaite","year":"2021","journal-title":"International journal of chronic obstructive pulmonary disease"},{"issue":"2","key":"pone.0302111.ref009","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1164\/rccm.167.2.211","article-title":"ATS\/ACCP Statement on cardiopulmonary exercise testing.","volume":"167","year":"2003","journal-title":"American journal of 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Sweden [in relation to power output only]: \"Reference equations for breathlessness during incremental cycle exercise testing\", ERJ Open Res.","volume":"9","author":"Dyspnea Society","year":"2023"},{"issue":"3","key":"pone.0302111.ref014","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1164\/rccm.201504-0841OC","article-title":"Common Mechanisms of Dyspnea in Chronic Interstitial and Obstructive Lung Disorders","volume":"193","author":"A Faisal","year":"2016","journal-title":"American journal of respiratory and critical care medicine"},{"key":"pone.0302111.ref015","first-page":"50","article-title":"Effect of morphine on breathlessness and exercise endurance in advanced COPD: a randomised crossover trial","author":"SJ Abdallah","year":"2017","journal-title":"The European respiratory journal"},{"issue":"5","key":"pone.0302111.ref016","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02494-2016","article-title":"Effects of hyperoxia on dyspnoea and exercise endurance in 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single photon emission computed tomography in patients without known coronary artery disease presenting with dyspnea","volume":"152","author":"B Balaravi","year":"2006","journal-title":"Am Heart J"},{"key":"pone.0302111.ref020","article-title":"Kliniska arbetsprov: metoder f\u00f6r diagnos och prognos.","author":"L Jorfeldt","year":"2013","journal-title":"Studentlitteratur"},{"issue":"4","key":"pone.0302111.ref021","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/cpf.12097","article-title":"Comparison of two commonly used reference materials for exercise bicycle tests with a Swedish clinical database of patients with normal outcome.","volume":"34","author":"L Brudin","year":"2014","journal-title":"Clin Physiol Funct Imaging"},{"key":"pone.0302111.ref022","first-page":"2047487320909667","article-title":"Age- and gender-specific upper limits and reference equations for workload-indexed systolic blood pressure response during bicycle ergometry","volume":"2020","author":"K 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grading of exercise capacity are clinically relevant.","volume":"40","author":"T Lindow","year":"2020","journal-title":"Clinical physiology and functional imaging."},{"issue":"5","key":"pone.0302111.ref029","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/j.1475-097X.1988.tb00218.x","article-title":"Physical working capacity determined by different types of bicycle exercise tests.","volume":"8","author":"L Wallin","year":"1988","journal-title":"Clin Physiol"},{"issue":"5","key":"pone.0302111.ref030","first-page":"377","article-title":"Psychophysical bases of perceived exertion","volume":"14","author":"GAV Borg","year":"1982","journal-title":"Medicine and Science in Sports and Exercise"},{"key":"pone.0302111.ref031","volume-title":"A Language and Environment for Statistical Computing","author":"R R Core Team","year":"2023"},{"key":"pone.0302111.ref032","volume-title":"Categorical data analysis.","author":"A. Agresti","year":"2013"},{"issue":"6","key":"pone.0302111.ref033","doi-asserted-by":"crossref","first-page":"00592","DOI":"10.1183\/23120541.00592-2023","article-title":"The modified Medical Research Council scale misclassifies exertional breathlessness among people referred for exercise testing.","volume":"9","author":"D Gustafsson","year":"2023","journal-title":"ERJ Open Research"},{"issue":"11","key":"pone.0302111.ref034","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1139\/apnm-2015-0179","article-title":"Physiological and perceptual responses to incremental exercise testing in healthy men: effect of exercise test modality.","volume":"40","author":"KM Muscat","year":"2015","journal-title":"Appl Physiol Nutr Metab"},{"issue":"9","key":"pone.0302111.ref035","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1249\/01.MSS.0000084593.56786.DA","article-title":"A treadmill ramp protocol using simultaneous changes in speed and grade.","volume":"35","author":"J Porszasz","year":"2003","journal-title":"Med Sci Sports Exerc"},{"key":"pone.0302111.ref036","unstructured":"Public Health Agency of Sweden. The National Public Health Survey 2004\u20132016. \u2018\u2018H\u00e4lsa p\u00e5 lika villkor, http:\/\/fohm-app.folkhalsomyndigheten.se\/Folkhalsodata\/pxweb\/sv\/A_Folkhalsodata\/. 2018."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0302111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T18:41:14Z","timestamp":1734547274000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0302111"}},"subtitle":[],"editor":[{"given":"Bharat Bhushan","family":"Sharma","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0302111","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]}}}