# A combined measure of blood leukocytes, forced vital capacity and quantitative CT is highly predictive of mortality in IPF: results of a single-centre cohort study

## TL;DR

A combination of blood leukocytes, lung function tests, and CT scans better predicts mortality in idiopathic pulmonary fibrosis patients than individual measures.

## Contribution

The study introduces a composite measure combining CT, FVC, and blood leukocytes to improve mortality prediction in IPF.

## Key findings

- Composite measures of CTvol, FVC, and TLF% outperformed single-variable measures in predicting mortality.
- Inclusion of blood leukocyte levels improved the predictive accuracy of mortality models.
- A composite variable with thresholds of ΔFVC >10%, ΔCTvol >10%, or ΔTLF% >10% was most predictive of mortality.

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic condition. Serial FVC monitoring is most commonly used to assess progression of disease but FVC does not always reflect regional CT change in IPF. Recently there has been growing interest in quantitative CT (qCT) assessment of IPF. In this study, we compared different physiological and qCT measurements of disease progression in predicting mortality in IPF.

We question if a composite measure of disease progression using qCT and FVC is more predictive of mortality than individual measurements, and if addition of blood leukocyte levels further enhance predictive ability of these measurements of disease progression.

We conducted a retrospective analysis of an IPF cohort (n = 71). Annualised change (∆) in CT-measured lung volume (CTvol) and total lung fibrosis score (TLF) were calculated (using the computer software CALIPER) together with annualised change in FVC and blood leukocyte levels within 4 months of first CT. These were modelled against mortality using multivariate Cox regression. Concordance indexes (C-statistic) of different Cox regression models were used to determine the most predictive and discriminative combination for mortality.

65 cases (91.5%) were male. Median (IQR) age 73.6 years (68.4–79.3). Death was reported in 24 cases (33.8%). The median annualised change in (∆)FVC was − 4.4% (-9.6-0.0), ∆TLF; + 2.9% (0.2-7.0), and ∆CTvol; -4.3% (0.0-10.9). Combined measurements of disease progression (∆CTvol, ∆FVC and ∆TLF%) out-performed single-variable measurements in predicting all-cause mortality in IPF. The composite variable of [ΔFVC >10%, ΔCTvol >10% or ΔTLF% >10%] was most predictive of mortality [HR 7.14 (2.45–20.79), p <0.001]. Inclusion of blood leukocytes improved C-statistic scores for each multivariate model.

Composite end points of ∆CTvol, ∆FVC and ∆TLF% were more predictive of mortality than single-variable measurements in this cohort. Inclusion of blood leukocytes into risk stratification models further improved mortality prediction for all measures of disease progression.

The online version contains supplementary material available at 10.1186/s12890-025-03825-4.

Idiopathic pulmonary fibrosis (IPF) is a behaviourally heterogeneous fibrotic condition. spirometry is most commonly used to assess progression of disease yet FVC is not always sensitive to regional morphologic changes observed radiologically in in IPF. Several human studies have implicated blood leukocytes (monocyte, neutrophil and lymphocyte) with disease progression and mortality.

In this study, we compared different measurements of disease progression (annualised change in FVC, CT-measured lung volume and CT-measured total lung fibrosis score) in predicting mortality in IPF. The use of composite end points of disease progression captured more cases of progression and were more predictive of mortality than single-variable measurements in this cohort. Inclusion of blood leukocytes improved risk stratification, suggesting inclusion can improve the discriminative ability of measurements of disease progression for mortality.

Assessing disease severity and accurately capturing disease progression in patients with IPF is a clinical priority that facilitates timely decision making regarding treatment initiation, assessment of treatment response and prognostication. In this context, the prospect of utilising easily measurable CT biomarkers could be an attractive adjunct to traditional FVC monitoring to capture cases of disease progression. Peripheral blood leukocytes have potential utility as a biomarker for identifying patients at greater risk of progression of IPF. This should be taken forward by prospective and validation studies.

The online version contains supplementary material available at 10.1186/s12890-025-03825-4.