{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:47:57Z","timestamp":1785743277345,"version":"3.56.0"},"reference-count":60,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302812\/2022\u20109"],"award-info":[{"award-number":["302812\/2022\u20109"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Abstract<\/jats:title>\n \n Traditional indices such as the \u2013 slope describe ventilatory efficiency within the submaximal, near\u2010linear domain of exercise but underrepresent the nonlinear ventilatory behaviour emerging beyond the first ventilatory threshold (VT\n 1<\/jats:sub>\n ). We applied a semi\u2010logarithmic model that linearizes the post\u2010VT\n 1<\/jats:sub>\n response by relating CO\n 2<\/jats:sub>\n output to log\u2010transformed ventilation, extracting an empirical slope (\n b_emp<\/jats:italic>\n ) and normalizing it to a theoretical upper limit of CO\n 2<\/jats:sub>\n clearance anchored to predicted maximal voluntary ventilation (MVV_pred), yielding the bounded ventilatory efficiency index . In 1150 rigorously screened healthy adults (52.4% women; median age 49 years), exhibited minimal sex\u2010related variation (14.3%\n vs<\/jats:italic>\n . 14.7%) and small positive associations with age (\u03b2\u00a0=\u00a0+0.058 \u00b1 0.007,\n P<\/jats:italic>\n \u00a0<\u00a00.0001) and FEV\n 1<\/jats:sub>\n _pred (%) (\u03b2\u00a0=\u00a0+0.032 \u00b1 0.008,\n P<\/jats:italic>\n \u00a0<\u00a00.0001), accounting for \u223c8.5% of total variance (\n R<\/jats:italic>\n 2<\/jats:sup>\n \u00a0=\u00a00.085). Both empirical (median 3.3 [2.7\u20134.1] L\u00b7logL\n \u2212<\/jats:sup>\n 1<\/jats:sup>\n ) and theoretical reference slopes (23.1 [19.5\u201327.3] L\u00a0logL\n \u2212<\/jats:sup>\n 1<\/jats:sup>\n ) declined with age, whereas remained stable across the lifespan, as confirmed by deterministic simulations demonstrating proportional coupling between ventilatory performance and theoretical capacity. In a\n post hoc<\/jats:italic>\n cohort of individuals without cardiopulmonary disease but with isolated diffusive disturbance, multivariable regression identified as the only significant independent predictor of reduced diffusing capacity (\n P<\/jats:italic>\n \u00a0=\u00a00.016), while age, height, sex and MVV_pred were non\u2010significant (all\n P<\/jats:italic>\n \u00a0>\u00a00.20), indicating physiological, rather than geometric, determinants. By referencing ventilatory performance to a theoretical limit of CO\n 2<\/jats:sub>\n removal, provides a reproducible, scale\u2010independent descriptor that refines the physiological interpretation of ventilatory efficiency across health, ageing and contrasting ventilatory constraints.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n The \u2013 slope and nadir underestimate key ventilatory adjustments during the most decisive phase of the exercise response \u2013 from the first ventilatory threshold (VT\n 1<\/jats:sub>\n ) to peak exercise.\n <\/jats:p>\n <\/jats:list-item>\n \n \n This study introduces a semi\u2010logarithmic approach that linearizes the decisive post\u2010VT\n 1<\/jats:sub>\n segment of the ventilatory response, better capturing its underlying physiological behaviour.\n <\/jats:p>\n <\/jats:list-item>\n \n The resulting slope, when normalized to a theoretical physiological limit for gas exchange and scaled to the predicted maximal voluntary ventilation, yields a bounded efficiency index (, %).<\/jats:p>\n <\/jats:list-item>\n \n remained robustly stable and only weakly associated with age and lung function, while showing no meaningful dependence on sex or height in over 1000 healthy adults, from which valuable normative equations were derived.<\/jats:p>\n <\/jats:list-item>\n \n This framework integrates ventilatory drive, gas exchange and diffusion capacity, offering a unified and easily applicable tool for physiological and clinical evaluation of ventilatory efficiency.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290456","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:25:38Z","timestamp":1781699138000},"page":"5777-5799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ventilatory efficiency: Physiological modelling and mechanistic validation"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-245X","authenticated-orcid":false,"given":"Paulo T","family":"Muller","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Pneumology Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Stubbe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B University Medicine B Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Ittermann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B University Medicine B Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlandson S","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Mathematical Institute, Biostatistical Department Federal University of Mato Grosso do Sul Campo Grande Mato Grosso do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Neder","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Division of Respirology, Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-9925","authenticated-orcid":false,"given":"Ralf","family":"Ewert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B University Medicine B Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"issue":"265","key":"e_1_2_9_2_1","first-page":"109","article-title":"Factors of safety in the structure of animals","volume":"67","author":"Alexander R. 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