Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct;211(10):1785-1793.
doi: 10.1164/rccm.202501-0208OC.

A Quantitative Imaging Measure of Progressive Pulmonary Fibrosis

Jennifer M Wang  1 , Ayodeji Adegunsoye  2 , Janelle Vu Pugashetti  1 , Cathryn T Lee  2 , Susan Murray  3 , Nisha Mohan  1 , Nazanin Nazemi  1 , Edward Kang  1 , Lydia Chelala  4 , Ella A Kazerooni  5 , Kevin R Flaherty  1 , Elizabeth A Belloli  1 , Jamie S Sheth  1 , David N O'Dwyer  1   6 , Mary E Strek  2 , Charles R Hatt  5   7 , MeiLan K Han  1 , Jonathan H Chung  2   8 , Justin M Oldham  1
Affiliations

A Quantitative Imaging Measure of Progressive Pulmonary Fibrosis

Jennifer M Wang et al. Am J Respir Crit Care Med. 2025 Oct.

Abstract

Rationale: 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. Objectives: 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). Methods: A retrospective cohort analysis was performed in individuals with fibrotic ILD, including idiopathic pulmonary fibrosis (n = 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 (n = 92). Measurements and Main Results: 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. Conclusions: Changes in qCT measures are associated with clinically relevant outcomes and could improve PPF classification.

Keywords: interstitial lung disease; quantitative computed tomography; survival.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram for the University of Michigan test cohort Definitions of abbreviations: CT = computed tomography; DLCO = diffusing capacity of the lungs for carbon monoxide; FVC = forced vital capacity
Figure 2:
Figure 2:
Kaplan Meier plots of two-year transplant-free survival (TFS) according to qctPPF classification in the a) University of Michigan and b) University of Chicago cohorts
Figure 3:
Figure 3:
Kaplan Meier plots of two-year transplant-free survival (TFS) according to qctPPF and radiologist-determined PPF (radPPF) classification
Figure 4:
Figure 4:
Kaplan Meier plots of two-year transplant-free survival (TFS) according to qctPPF and physiological PPF (pftPPF) classification
See this image and copyright information in PMC

Comment in

References

    1. Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, Kreuter M, Lynch DA, Maher TM, Martinez FJ, Molina-Molina M, Myers JL, Nicholson AG, Ryerson CJ, Strek ME, Troy LK, Wijsenbeek M, Mammen MJ, Hossain T, Bissell BD, Herman DD, Hon SM, Kheir F, Khor YH, Macrea M, Antoniou KM, Bouros D, Buendia-Roldan I, Caro F, Crestani B, Ho L, Morisset J, Olson AL, Podolanczuk A, Poletti V, Selman M, Ewing T, Jones S, Knight SL, Ghazipura M, Wilson KC. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022; 205: e18–e47. - PMC - PubMed
    1. Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R, Goeldner RG, Clerisme-Beaty E, Tetzlaff K, Cottin V, Wells AU. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J 2020; 55. - PMC - PubMed
    1. Rajan SK, Cottin V, Dhar R, Danoff S, Flaherty KR, Brown KK, Mohan A, Renzoni E, Mohan M, Udwadia Z, Shenoy P, Currow D, Devraj A, Jankharia B, Kulshrestha R, Jones S, Ravaglia C, Quadrelli S, Iyer R, Dhooria S, Kolb M, Wells AU. Progressive pulmonary fibrosis: an expert group consensus statement. Eur Respir J 2023; 61. - PMC - PubMed
    1. Lynch DA, Godwin JD, Safrin S, Starko KM, Hormel P, Brown KK, Raghu G, King TE Jr., Bradford WZ, Schwartz DA, Richard Webb W, Idiopathic Pulmonary Fibrosis Study G. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005; 172: 488–493. - PubMed
    1. Kelly CA, Saravanan V, Nisar M, Arthanari S, Woodhead FA, Price-Forbes AN, Dawson J, Sathi N, Ahmad Y, Koduri G, Young A, British Rheumatoid Interstitial Lung N. Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study. Rheumatology (Oxford) 2014; 53: 1676–1682. - PubMed