Associations of interstitial lung disease subtype and CT pattern with lung function and survival

John S Kim¹, Janelle Pugashetti², Shwu-Fan Ma³, Yong Huang³, Anna J Podolanczuk⁴, David A Lynch⁵, Andrea Oh⁶, Josyf Mychaleckyj⁷, Ani Manichaikul⁷, Stephen Rich⁷, Felix Chua⁸, Traci M Adams⁹, Kevin R Flaherty², Joyce S Lee¹⁰, Joseph A Lasky¹¹, Ganesh Raghu¹², Susan Murray¹³, Catherine Spino¹³, Fernando J Martinez¹⁴, Imre Noth³, Stephen M Humphries⁵, Ayodeji Adegunsoye¹⁵, Philip L Molyneaux⁸, Justin M Oldham², Chad A Newton⁹

Affiliations

¹ Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA jk6jb@uvahealth.org.
² Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
³ Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
⁴ Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
⁵ Radiology, National Jewish Health, Denver, Colorado, USA.
⁶ Department of Radiology, University of California Los Angeles, Los Angeles, California, USA.
⁷ Department of Genome Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
⁸ Department of Respiratory Medicine, Royal Brompton Hospital, Guy's and St. Thomas's NHS Foundation Trust and National Heart and Lung Institute Imperial College London, London, UK.
⁹ Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹⁰ Department of Medicine, University of Colorado, Denver, Colorado, USA.
¹¹ Medicine, Tulane University, New Olreans, Louisiana, USA.
¹² University of Washington, Seattle, Washington, USA.
¹³ Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Department of Medicine, University of Massachusetts Chan Medical School-UMass Memorial Health System, Worcester, Massachusetts, USA.
¹⁵ Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA.

PMID: 40484639
PMCID: PMC12354206
DOI: 10.1136/thorax-2024-222149

Associations of interstitial lung disease subtype and CT pattern with lung function and survival

John S Kim et al. Thorax. 2025.

. 2025 Jun 8:thorax-2024-222149.

doi: 10.1136/thorax-2024-222149. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA jk6jb@uvahealth.org.
² Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
³ Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
⁴ Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
⁵ Radiology, National Jewish Health, Denver, Colorado, USA.
⁶ Department of Radiology, University of California Los Angeles, Los Angeles, California, USA.
⁷ Department of Genome Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
⁸ Department of Respiratory Medicine, Royal Brompton Hospital, Guy's and St. Thomas's NHS Foundation Trust and National Heart and Lung Institute Imperial College London, London, UK.
⁹ Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹⁰ Department of Medicine, University of Colorado, Denver, Colorado, USA.
¹¹ Medicine, Tulane University, New Olreans, Louisiana, USA.
¹² University of Washington, Seattle, Washington, USA.
¹³ Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Department of Medicine, University of Massachusetts Chan Medical School-UMass Memorial Health System, Worcester, Massachusetts, USA.
¹⁵ Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA.

PMID: 40484639
PMCID: PMC12354206
DOI: 10.1136/thorax-2024-222149

Abstract

Background: Prior work suggests different interstitial lung diseases (ILDs) that share the radiological usual interstitial pneumonia (UIP) pattern have an overall worse prognosis. However, epidemiological data with longitudinal sampling and replication remains lacking.

Methods: Data was used from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=932) and a meta-cohort of ILD research studies (n=1579). Linear mixed-effects models and Cox proportional hazard models were used to determine forced vital capacity (FVC) slopes and 5-year transplant-free survival, respectively, by ILD diagnosis and UIP radiological pattern. Secondarily, we examined FVC and survival by diagnosis and radiological fibrosis quantified by data-driven texture analysis (DTA) in the PFF-PR. Models were adjusted for age, sex, smoking and antifibrotic and immunosuppression medication use.

Results: The proportions of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease (CTD)-ILD were the following for PFF-PR (70%, 11%, 19%) and meta-cohort (21%, 32%, 47%). In the PFF-PR, CTD-ILD with UIP CT pattern was associated with slower FVC decline (-34.4 mL/year) compared with IPF (-158.4 mL/year) and longer transplant-free survival (HR 0.50, 95% CI 0.29 to 0.85). This was replicated in the meta cohort for FVC (-53.1 vs -185.9 mL/year, p<0.0001) and survival (HR 0.38, 95% CI 0.27 to 0.53). A similar pattern was seen using DTA to objectively categorise patients into higher and lower radiological fibrosis. Between IPF and FHP-UIP, FVC decline was not significantly different in the PFF-PR (-203.4 vs -158.4 mL/year, p=0.58) and meta-cohort (-124.0 vs -185.9 mL/year, p=0.25).

Conclusions: Even in the presence of a UIP CT pattern, there may still be differences in lung function over time and survival, particularly for CTD-ILD.

Keywords: Idiopathic pulmonary fibrosis; Imaging/CT MRI etc; Interstitial Fibrosis.

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Conflict of interest statement

Competing interests: AP reports consulting fees from Regeneron and Boehringer Ingelheim. DAL reports consulting fees from Boehringer Ingelheim and Calyx and US patents (#10,706,533, #11,468,564, #11,494,902). FC reports speaker’s honoraria from Boehringer Ingelheim for educational events. KRF reports receiving personal fees from Boehringer Ingelheim, Roche/Genentech, Bellerophon, Shionogi, DevPro, AstraZeneca, Pure Health, Horizon, FibroGen, Sun Pharmaceuticals, Pliant, United Therapeutics, Arrowhead, Lupin, Polarean, PureTech, Trevi Therapeutics, CSL Behring, Daewoong, DisperSol, Immumet, NeRRe Therapeutics, Insilco and Vicore outside the submitted work. JSL reports grants from the NIH and Boehringer Ingelheim, outside the submitted work, has received an unrestricted research gift from Pliant, outside the submitted work, consulting fees from Blade, Boehringer Ingelheim, United Therapeutics, Astra Zenca and Eleven P15, outside the submitted work, has served on data safety monitoring board for United Therapeutics and Avalyn and is an advisor for the Pulmonary Fibrosis Foundation, outside the submitted work. FJM reports grant support from the NHLBI that supported the data collection of the parent study, grant or contracts from Afferent/Merck, Boehringer Ingelheim, Biogen, Bristol Myers Squibb, DevPro, Nitto, Patara/Respivant, ProMedior/Roche, consult fees from Boehringer Ingelheim, Bristol Myers Squibb, Hoffman/Laroche, IQVIA, Lung Therapuetics, Novartis, Sanofi, Shionogi, Two XR, Veracyte, payment or honoraria from Boehringer Ingelheim, support for attending meetings/travel from Boehringer Ingelehim for international meeting, participation of data safety monitoring board for Boehringer Ingelheim and Biogen. IN reports personal fees from Boehringer Ingelheim, personal fees from Genentech, personal fees from Confo, outside the SMH reports grant support from Calyx, Boehringer Ingelheim and Veracyte, consulting fees from Lyra Therapeutics and Veracyte and US patents (#10,706,533, #11,468,564, #11,494,902). AA has received research grants from the Pulmonary Fibrosis Foundation, the American College of Chest Physicians and the National Institutes of Health for the conduct of studies in pulmonary fibrosis and served on a pulmonary fibrosis educational forum for Boehringer Ingelheim, as well as consultancy for Roche Pharmaceuticals, Boehringer Ingelheim, Inogen and Medscape. PLM reports grant support from AstraZeneca and fees from Hoffmann-La Roche, Boehringer Ingelheim, AstraZeneca, Trevi, Qureight and Endevour and stock options in Qureight. JO reports fees and support from Boehringer Ingelheim, Roche, Lupin and Gatehouse Bio and DMC for Genentech, Endeavor BioMedicines and Novartis. CAN reports consulting fees for Boehringer Ingelheim.

Figures

**Figure 1.**
Consort diagram of participants.

**Figure 2.**
Associations of interstitial lung disease diagnosis with 5-year transplant-free survival in (A) Pulmonary Fibrosis Foundation Patient Registry and (B) meta-cohort. Hazard ratio estimates from Cox proportional hazard models adjusted for age, sex, smoking history, body mass index, baseline forced vital capacity and diffusing capacity for carbon monoxide, and history of antifibrotic and immunosuppression use. Study center adjusted for in meta-cohort analysis. Abbreviations: CTD-ILD: connective tissue disease-interstitial lung disease; FHP=fibrotic hypersensitivity pneumonitis; IPF=idiopathic pulmonary fibrosis; UIP=usual interstitial pneumonia

**Figure 3.**
(A) Boxplots of data-driven texture analysis (DTA) fibrosis scores by diagnosis of interstitial lung disease. P-values from t-test comparing mean DTA-fibrosis scores between interstitial lung disease diagnosis. (B) Associations of diagnosis with high and low DTA fibrosis scores with changes in forced vital capacity. Estimates generated from linear mixed-effects models with random intercept and slope and adjusted for age, sex, smoking history, body mass index, and history of antifibrotic and immunosuppression use. Abbreviations: CTD-ILD: connective tissue disease-interstitial lung disease; FHP=fibrotic hypersensitivity pneumonitis; IPF=idiopathic pulmonary fibrosis

See this image and copyright information in PMC

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Associations of interstitial lung disease subtype and CT pattern with lung function and survival

Affiliations

Associations of interstitial lung disease subtype and CT pattern with lung function and survival

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials