Physiological quotients and mortality: redefining lung function interpretation beyond FEV ₁

Background The FEV 1 Q is a physiological quotient reflecting the distance a measured FEV 1 is from a 1st percentile (minimally survivable) value. We aimed to derive physiological quotients for other lung function measures and assess their association with all-cause mortality. Methods We analysed data from adults referred for lung function testing at Cambridge University Hospital (CUH) and Royal Papworth Hospital (RPH) between 2016 and 2024. We investigated the stability of the 1st percentiles for FEV 1 , FVC, FEV 1 /FVC, DLCO, KCO, VA, and TLC stratified by sex and age group by visualising the overlap of 95% confidence intervals. We calculated physiological quotients for each parameter (measured value/1st percentile) and investigated their association with all-cause mortality using Cox regression analysis. We used Harrell's C statistics to compare discriminative performance. Results We analysed data from 7717 CUH patients and 6054 RPH patients. At CUH, 51% were female, compared to 45% at RPH. Mean age was 57.9 ( sd 14.9) years at CUH and 62.7 ( sd 14.8) at RPH. 1st percentile values were generally consistent across age groups but different for males and females for FEV 1 , FVC, VA, and TLC. For FEV 1 /FVC, DLCO, and KCO 1st percentile values were generally stable across both age and sex. Mean follow-up times were 5.8 ( sd 2.6) years at CUH and 5.5 ( sd 2.7) years at RPH, during which time 19% and 39% of patients died respectively. Physiological quotients had higher Harrell's C statistics, indicating better discrimination of survival than lung function expressed as raw units, z-scores and percent predicted. Conclusion Physiological quotients have greater discriminative ability in the prediction of all-cause mortality than existing metrics, providing an alternative standard for lung function interpretation.