A Quantitative Imaging Measure of Progressive Pulmonary Fibrosis.

Abstract

<b>Rationale:</b> Progressive pulmonary fibrosis (PPF) is common in patients with fibrotic interstitial lung disease (ILD) and leads to high mortality. Although PPF guideline criteria include computed tomography (CT)-based progression, these measures are qualitative and prone to interreader variability. Quantitative computed tomography (qCT) measurements have the potential to overcome this limitation. <b>Objectives:</b> The objectives of this study were to determine whether changes in qCT measures of pulmonary fibrosis are associated with transplant-free survival (TFS) in a diverse ILD cohort and establish a quantitative computed tomography measure of progressive pulmonary fibrosis (qctPPF). <b>Methods:</b> A retrospective cohort analysis was performed in individuals with fibrotic ILD, including idiopathic pulmonary fibrosis (<i>n</i> = 350), who underwent serial chest CT for clinical indications. Commercially available software was used to generate qCT measures of pulmonary fibrosis, which were tested for association with 2-year TFS using a multivariable Cox proportional hazards model. Iterative modeling was then performed to develop a composite qctPPF measure. Results were validated in an independent ILD cohort (<i>n</i> = 92). <b>Measurements and Main Results:</b> Increasing ground-glass opacity and decreasing lung volume showed consistent association with decreased TFS across cohorts when modeled continuously and dichotomously. qctPPF classification was associated with a greater than threefold increased hazard of death or transplant in the test (hazard ratio, 4.41; 95% confidence interval, 2.77-7.03) and validation (hazard ratio, 3.54; 95% confidence interval, 1.62-7.71) cohorts. Agreement between qctPPF and radiologist-determined PPF was poor (κ = 0.20), with qctPPF classification maintaining prognostic significance when discordant with radiologist interpretation. <b>Conclusions:</b> Changes in qCT measures are associated with clinically relevant outcomes and could improve PPF classification.