Impact of Reference Equations and Lower Limit of Normal Definitions on Lung Function Score Calculation

It is unclear if recent updates to pulmonary function testing (PFT) guidelines impact calculation of the Lung Function Score (LFS), which is based on FEV1 and DLCO and is associated with post-stem cell transplant (SCT) survival.

To recalculate the LFS according to the updated PFT guidelines and test if an abnormal LFS using updated PFT guidelines is associated with post-SCT mortality.

This was a secondary analysis of a dataset of children aged 6-21 years who underwent SCT. The LFS was calculated using 6 different definitions (defined using one of three reference equations and z-score or % predicted (%pred) thresholds). We examined the association of an abnormal LFS (>2) with post-SCT survival using Kaplan-Meier curves and Cox proportional hazard regression models adjusted for site and race.

Of the 278 children included, 67-81% had an abnormal LFS, depending on LFS definition. Children with an abnormal LFS defined using NHANES reference equations and %pred had 120% increased hazard of death compared to those with a normal LFS (adjusted hazard ratio [aHR]=2.20, 95% confidence interval [CI]=1.30 to 3.74, P = .003). Using GLI race-neutral reference equations and %pred, an abnormal LFS was associated with a 60% increased hazard of death (aHR = 1.60, 95% CI = 1.05 to 2.46, P = .03), while an abnormal LFS calculated using GLI race-neutral reference equations and z-scores was not associated with mortality (aHR = 1.17, 95% CI = 0.80 to 1.72, P = .4).

Choice of reference equations and thresholds impacted the LFS calculation. While the original LFS using NHANES reference data and %pred was associated with mortality, having an abnormal LFS calculated using the current PFT guidelines was not associated with an increased risk of death.