Physiological quotients and mortality: redefining lung function interpretation beyond FEV₁

Forced expiratory volume in 1 s quotient (FEV₁Q) is a physiological quotient reflecting the distance a measured FEV₁ 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.

We analysed data from adults referred for lung function testing at Cambridge University Hospital (CUH) and Royal Papworth Hospital (RPH) in the UK between 2016 and 2024. We investigated the stability of the 1st percentiles for FEV₁, forced vital capacity (FVC), FEV₁/FVC, diffusing capacity of the lung for carbon monoxide (D _LCO), transfer coefficient of the lung for carbon monoxide (K _CO), alveolar volume (V _A) and total lung capacity (TLC) stratified by sex and age group by visualising the overlap of 95% confidence intervals. We calculated physiological quotients for each parameter (Q=measured value/1st percentile value) and investigated their association with all-cause mortality using Cox regression analysis. We used Harrell's C-index to compare discriminative performance.

We analysed data from 7717 CUH patients and 6054 RPH patients. At CUH, 51% were female compared with 45% at RPH. Mean±sd age was 57.9±14.9 years at CUH and 62.7±14.8 years at RPH. 1st percentile values were generally consistent across age groups but different for males and females for FEV₁, FVC, V _A and TLC. For FEV₁/FVC, D _LCO and K _CO, 1st percentile values were generally stable across both age and sex. Mean±sd follow-up times were 5.8±2.6 years at CUH and 5.5±2.7 years at RPH, during which time 19% and 39% of patients died, respectively. Physiological quotients had higher Harrell's C-indexes, indicating better discrimination of survival than lung function expressed as raw units, z-scores and percent predicted.

Physiological quotients have greater discriminative ability in the prediction of all-cause mortality than existing metrics, providing an alternative standard for lung function interpretation.