# An updated comparison of standard and novel FEV1 indices’ association with all-cause mortality

## TL;DR

This study compares different FEV1 indices to see which best predict mortality, finding that some newer indices are more strongly linked to death risk than traditional ones.

## Contribution

The study introduces and evaluates novel FEV1 indices that show stronger associations with mortality than standard reference-range-dependent indices.

## Key findings

- FEV1/Ht3 and FEV1/Ht2 indices showed the highest hazard ratios for mortality after adjustment.
- Reference-range-independent FEV1 indices are equally or more strongly associated with mortality than traditional indices.
- C-statistic remained consistent across all indices in adjusted analyses.

## Abstract

Current recommendations for defining FEV1 abnormalities are based on Z-score cutoffs. Alternative approaches may better correlate with patient-related outcomes, including mortality.

This study evaluates the association between FEV1 value and mortality in six FEV1 indices in a large, U.S based cohort.

This is a cohort of 2007–2012 National Health and Nutrition Examination Study (NHANES) participants with spirometry and linked mortality data through 2019. We transformed FEV1 values to the following indices: raw FEV1, FEV1-Z scores (FEV1-Z), FEV1-Percent Predicted (FEV1-PP), FEV1/Height2 (FEV1/Ht2), FEV1/Height3 (FEV1/Ht3), and FEV1-Q. We compared association with all-cause mortality between lowest and highest FEV1 deciles of each index using Cox Proportional Hazards models. Two sensitivity analyses were performed, one after applying NHANES sample weighting and one including lower quality spirometry. A subgroup analysis of participants with airflow obstruction, defined as FEV1/FVC ≤ LLN, was performed.

Of the 12,994 included participants, 971 (7.5%) had died. The majority (56.2%) were nonsmokers and 13.2% had an FEV1/FVC < LLN. When comparing the most to least severe deciles of FEV1, the indices with the largest magnitude unadjusted hazard ratios were FEV1/ht3 (HR 26.4, 95%CI 16.0–43.6), FEV1/ht2 (HR 21.8, 95%CI 13.8–34.7), FEV1-Q (HR 17.5, 95%CI 11.6–26.5), and FEV1 (HR 14.4, 95%CI 9.7–21.5). After adjusting for age, gender, and tobacco pack-years, FEV1/Ht3 (HR 4.9, 95%CI 2.6–9.3) and FEV1/Ht2 (HR 4.8, 95%CI 2.7–8.7) had the highest hazard ratios, however the confidence intervals had significant overlap with other indices. In adjusted analyses, the C-statistic (0.81) was the same across indices. Sensitivity and subgroup analyses yielded a similar pattern.

Reference-range-independent indices based on absolute FEV1 (raw FEV1, FEV1-Q, FEV1/Ht2, FEV1/Ht3) are equally or more strongly associated with mortality than reference-range- dependent FEV1 indices (FEV1-Z scores, FEV1-Percent Predicted) in a large U.S. cohort.