Physiological quotients for discriminating mortality and respiratory outcomes: a UK biobank cohort study
File(s)
Published version (early view)
Author(s)
Knox-Brown, Ben
Sylvester, Karl
Amaral, Andre
Type
Journal Article
Abstract
Background
Spirometry is traditionally interpreted using reference-based metrics derived from equations such as those from the Global Lung Function Initiative (GLI). Physiological quotients, which express lung function relative to a lower physiological boundary, have been proposed as an alternative approach. We aimed to compare the prognostic performance of physiological quotients with conventional reference-based metrics including both the GLI 2012 ethnicity-specific and the GLI 2023 Global equations, in a large population-based cohort.
Methods
We analysed data from 270,599 UK Biobank participants aged 40–69 years with baseline spirometry. Physiological quotients were calculated for FEV₁, FVC, and FEV₁/FVC using previously established first percentile boundaries. Associations with all-cause and cause-specific mortality, respiratory hospitalisation, respiratory symptoms, and self-reported respiratory diagnoses were examined using Cox proportional hazards and logistic regression models.
Results
Over a median follow-up of 15.7 years, 26,197 (10%) participants died. Lower physiological quotients were consistently associated with adverse outcomes. Each 1-SD decrement in FEV₁Q, FVCQ, and FEV₁/FVCQ was associated with higher all-cause mortality (HRs 1.06–1.09), cardiovascular mortality (HRs 1.06–1.20), respiratory mortality (HRs 1.28–1.77), and respiratory hospitalisation (HRs 1.04–1.41). Discrimination for all-cause mortality was modest (C-statistics 0.64–0.65), moderate for cardiovascular mortality (0.72–0.73), and good for respiratory mortality (0.76–0.79). Discrimination of respiratory hospitalisation was modest but slightly higher for FEV₁Q and FVCQ (0.65) than for percent predicted values and z-scores (0.61–0.62). Across mortality outcomes, discriminative performance was similar between physiological quotients, percent predicted values, and z-scores.
Conclusion
Physiological quotients demonstrated prognostic performance comparable to conventional reference-based spirometric metrics for mortality outcomes, while showing modest advantages for respiratory morbidity.
Spirometry is traditionally interpreted using reference-based metrics derived from equations such as those from the Global Lung Function Initiative (GLI). Physiological quotients, which express lung function relative to a lower physiological boundary, have been proposed as an alternative approach. We aimed to compare the prognostic performance of physiological quotients with conventional reference-based metrics including both the GLI 2012 ethnicity-specific and the GLI 2023 Global equations, in a large population-based cohort.
Methods
We analysed data from 270,599 UK Biobank participants aged 40–69 years with baseline spirometry. Physiological quotients were calculated for FEV₁, FVC, and FEV₁/FVC using previously established first percentile boundaries. Associations with all-cause and cause-specific mortality, respiratory hospitalisation, respiratory symptoms, and self-reported respiratory diagnoses were examined using Cox proportional hazards and logistic regression models.
Results
Over a median follow-up of 15.7 years, 26,197 (10%) participants died. Lower physiological quotients were consistently associated with adverse outcomes. Each 1-SD decrement in FEV₁Q, FVCQ, and FEV₁/FVCQ was associated with higher all-cause mortality (HRs 1.06–1.09), cardiovascular mortality (HRs 1.06–1.20), respiratory mortality (HRs 1.28–1.77), and respiratory hospitalisation (HRs 1.04–1.41). Discrimination for all-cause mortality was modest (C-statistics 0.64–0.65), moderate for cardiovascular mortality (0.72–0.73), and good for respiratory mortality (0.76–0.79). Discrimination of respiratory hospitalisation was modest but slightly higher for FEV₁Q and FVCQ (0.65) than for percent predicted values and z-scores (0.61–0.62). Across mortality outcomes, discriminative performance was similar between physiological quotients, percent predicted values, and z-scores.
Conclusion
Physiological quotients demonstrated prognostic performance comparable to conventional reference-based spirometric metrics for mortality outcomes, while showing modest advantages for respiratory morbidity.
Date Issued
2026-08-06
Date Acceptance
2026-07-21
Citation
ERJ Open Research, 2026
ISSN
2312-0541
Publisher
European Respiratory Society
Journal / Book Title
ERJ Open Research
Copyright Statement
© The authors 2026. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org
License URL
Publication Status
Published online
Date Publish Online
2026-08-06