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

Area of Science:

• Pulmonary Medicine
• Hematology
• Pediatric Oncology

Background:

• Pulmonary function testing (PFT) guidelines have been updated, potentially affecting the Lung Function Score (LFS) calculation.
• The Lung Function Score (LFS), based on FEV1 and DLCO, is a known predictor of survival post-stem cell transplant (SCT).
• The impact of updated PFT guidelines on LFS calculation and its association with post-SCT mortality remains unclear.

Purpose of the Study:

• To recalculate the LFS using updated PFT guidelines.
• To determine if an abnormal LFS, calculated with current PFT guidelines, is associated with post-SCT mortality.

Main Methods:

• Secondary analysis of a dataset of pediatric patients (aged 6-21 years) who underwent SCT.
• Calculated LFS using six different definitions based on three reference equations and z-score or % predicted thresholds.
• Examined the association between an abnormal LFS (>2) and post-SCT survival using Kaplan-Meier curves and adjusted Cox proportional hazard regression models.

Main Results:

• The percentage of patients with an abnormal LFS varied from 67-81% depending on the definition used.
• An abnormal LFS calculated using NHANES reference equations and % predicted was associated with a 120% increased hazard of death (aHR=2.20).
• An abnormal LFS using GLI race-neutral equations and % predicted showed a 60% increased hazard of death (aHR=1.60), but not when using z-scores (aHR=1.17).

Conclusions:

• The choice of reference equations and thresholds significantly influences LFS calculation.
• While the original LFS definition using NHANES data was linked to mortality, an abnormal LFS based on current PFT guidelines did not show a significant association with increased mortality risk.
• This suggests that updated PFT guidelines may alter the predictive value of LFS for post-SCT survival.