{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:40:58Z","timestamp":1791582058400,"version":"4.3.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (V7 o2peak) following rigorous adjustment for other predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death\/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V7 o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944\u20130.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951\u20130.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041\u20131.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007\u20131.115) (all P\u2009&amp;lt;\u20090.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CPET provides additional prognostic information to established predictors of death\/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201806-1110oc","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T17:50:11Z","timestamp":1539625811000},"page":"987-995","source":"Crossref","is-referenced-by-count":129,"title":["Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis"],"prefix":"10.1093","volume":"199","author":[{"given":"Helge","family":"Hebestreit","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik H. J.","family":"Hulzebos","sequence":"additional","affiliation":[{"name":"Child Development & Exercise Center, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Schneiderman","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Karila","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et Allergologie P\u00e9diatriques, Centre de Ressources et Comp\u00e9tences dans la Mucoviscidose, H\u00f4pital Necker Enfants Malades, Universit\u00e9 Paris V \u2013 Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Boas","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susi","family":"Kriemler","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Discipline of Physiotherapy, Faculty of Health Sciences and"},{"name":"Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia"},{"name":"Central Clinical School, Sydney Medical School, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Sahlberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don S.","family":"Urquhart","sequence":"additional","affiliation":[{"name":"Department of Paediatric Respiratory and Sleep Medicine, Royal Hospital for Sick Children, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry C.","family":"Lands","sequence":"additional","affiliation":[{"name":"Montreal Children\u2019s Hospital, McGill University Health Centre, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Ratjen","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Takken","sequence":"additional","affiliation":[{"name":"Child Development & Exercise Center, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liobou","family":"Varanistkaya","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"R\u00fccker","sequence":"additional","affiliation":[{"name":"Institute for Clinical Epidemiology and Biometry, Wuerzburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hebestreit","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Usemann","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-1070","authenticated-orcid":false,"given":"Thomas","family":"Radtke","sequence":"additional","affiliation":[{"name":"Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,4,15]]},"reference":[{"key":"2026030321271417300_bib1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1136\/thx.52.4.313","article-title":"A prognostic model for the prediction of survival in cystic fibrosis","volume":"52","author":"Hayllar","year":"1997","journal-title":"Thorax"},{"key":"2026030321271417300_bib2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jcf.2009.04.001","article-title":"An overview of international literature from cystic fibrosis registries: 1. Mortality and survival studies in cystic fibrosis","volume":"8","author":"Buzzetti","year":"2009","journal-title":"J Cyst Fibros"},{"key":"2026030321271417300_bib3","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.clnu.2012.08.017","article-title":"Stunting is an independent predictor of mortality in patients with cystic fibrosis","volume":"32","author":"Vieni","year":"2013","journal-title":"Clin Nutr"},{"key":"2026030321271417300_bib4","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1056\/NEJM199212173272504","article-title":"The prognostic value of exercise testing in patients with cystic fibrosis","volume":"327","author":"Nixon","year":"1992","journal-title":"N Engl J Med"},{"key":"2026030321271417300_bib5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/thx.52.3.291","article-title":"Exercise testing and prognosis in adult cystic fibrosis","volume":"52","author":"Moorcroft","year":"1997","journal-title":"Thorax"},{"key":"2026030321271417300_bib6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1136\/thx.2003.008102","article-title":"Peak oxygen uptake and mortality in children with cystic fibrosis","volume":"60","author":"Pianosi","year":"2005","journal-title":"Thorax"},{"key":"2026030321271417300_bib7","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1249\/MSS.0000000000000344","article-title":"Prediction of mortality in adolescents with cystic fibrosis","volume":"46","author":"Hulzebos","year":"2014","journal-title":"Med Sci Sports Exerc"},{"key":"2026030321271417300_bib8","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1164\/rccm.2105090","article-title":"An elevated breathing reserve index at the lactate threshold is a predictor of mortality in patients with cystic fibrosis awaiting lung transplantation","volume":"165","author":"Tantisira","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030321271417300_bib9","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1183\/09031936.00086211","article-title":"Chronic infection and inflammation affect exercise capacity in cystic fibrosis","volume":"39","author":"van de Weert-van Leeuwen","year":"2012","journal-title":"Eur Respir J"},{"key":"2026030321271417300_bib10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/01621459.1963.10500845","article-title":"Hierarchical grouping to optimize an objective function","volume":"58","author":"Ward","year":"1963","journal-title":"J Am Stat Assoc"},{"key":"2026030321271417300_bib11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/cs0400419","article-title":"Cardio-respiratory response to exercise in normal children","volume":"40","author":"Godfrey","year":"1971","journal-title":"Clin Sci"},{"key":"2026030321271417300_bib12","first-page":"141","article-title":"Assessment of exercise pulmonary function","volume-title":"Pediatric laboratory exercise testing clinical guidelines","author":"Orenstein","year":"1993"},{"key":"2026030321271417300_bib13","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur Respir J"},{"key":"2026030321271417300_bib14","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/ejcn.2010.8","article-title":"Body mass index percentiles for children and adolescents in Germany based on a nationally representative sample (KiGGS 2003-2006)","volume":"64","author":"Rosario","year":"2010","journal-title":"Eur J Clin Nutr"},{"key":"2026030321271417300_bib15","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1055\/s-0030-1253666","article-title":"[Percentiles of body mass index of 18-80-year-old German adults based on data from the Second National Nutrition Survey]","volume":"135","author":"Hemmelmann","year":"2010","journal-title":"Dtsch Med Wochenschr"},{"key":"2026030321271417300_bib16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.7326\/M13-0636","article-title":"Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry","volume":"161","author":"MacKenzie","year":"2014","journal-title":"Ann Intern Med"},{"key":"2026030321271417300_bib17","doi-asserted-by":"crossref","first-page":"d1008","DOI":"10.1136\/bmj.d1008","article-title":"Improved survival at low lung function in cystic fibrosis: cohort study from 1990 to 2007","volume":"342","author":"George","year":"2011","journal-title":"BMJ"},{"key":"2026030321271417300_bib18","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJM199204303261804","article-title":"Prediction of mortality in patients with cystic fibrosis","volume":"326","author":"Kerem","year":"1992","journal-title":"N Engl J Med"},{"key":"2026030321271417300_bib19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1513\/AnnalsATS.201707-570OC","article-title":"CFTR genotype and maximal exercise capacity in cystic fibrosis: a cross-sectional study","volume":"15","author":"Radtke","year":"2018","journal-title":"Ann Am Thorac Soc"},{"key":"2026030321271417300_bib20","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1378\/chest.130.5.1441","article-title":"CFTR genotype as a predictor of prognosis in cystic fibrosis","volume":"130","author":"McKone","year":"2006","journal-title":"Chest"},{"key":"2026030321271417300_bib21","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/thx.2004.031153","article-title":"Genotype-phenotype correlation for pulmonary function in cystic fibrosis","volume":"60","author":"de Gracia","year":"2005","journal-title":"Thorax"},{"key":"2026030321271417300_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.healun.2014.06.014","article-title":"A consensus document for the selection of lung transplant candidates: 2014\u2014an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation","volume":"34","author":"Weill","year":"2015","journal-title":"J Heart Lung Transplant"},{"key":"2026030321271417300_bib23","first-page":"CD002768","article-title":"Physical exercise training for cystic fibrosis","volume":"11","author":"Radtke","year":"2017","journal-title":"Cochrane Database Syst Rev"}],"updated-by":[{"DOI":"10.1164\/rccm.v202erratum3","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000}}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/199\/8\/987\/67115460\/ajrccm_199_8_987.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/199\/8\/987\/67115460\/ajrccm_199_8_987.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:27:20Z","timestamp":1772591240000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/199\/8\/987\/8497921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":23,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,4,15]]},"published-print":{"date-parts":[[2019,4,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201806-1110oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,4]]},"published":{"date-parts":[[2019,4]]}}}