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ORIGINAL RESEARCH article

Front. Med.

Sec. Pulmonary Medicine

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1679011

Changes in lung function and exercise capacity are strong predictors of mortality in patients with IPF receiving antifibrotic therapy

Provisionally accepted
Ju Hyun OhJu Hyun Oh1Moo Suk ParkMoo Suk Park2Man Pyo ChungMan Pyo Chung3Sung Hwan JeongSung Hwan Jeong4Jin Woo SongJin Woo Song5Sun Mi ChoiSun Mi Choi6Yong Hyun KimYong Hyun Kim7Sung Woo ParkSung Woo Park8Yangin JegalYangin Jegal9Hee-Young YoonHee-Young Yoon10Won-Il ChoiWon-Il Choi11Jung-Wan YooJung-Wan Yoo12Hyun-kyung LeeHyun-kyung Lee13세훈 양세훈 양14Eun-Joo LeeEun-Joo Lee15HYE SOOK CHOIHYE SOOK CHOI16Hyung Koo KangHyung Koo Kang17Jong Sun ParkJong Sun Park18*Jae Ha LeeJae Ha Lee19*
  • 1Ajou University Medical Center, Suwon-si, Republic of Korea
  • 2Yonsei University College of Medicine, Seodaemun-gu, Republic of Korea
  • 3Sungkyunkwan University School of Medicine, Suwon-si, Republic of Korea
  • 4Gachon University Gil Medical Center, Namdong-gu, Republic of Korea
  • 5Asan Medical Center, Songpa-gu, Republic of Korea
  • 6Seoul National University College of Medicine, Jongno-gu, Republic of Korea
  • 7The Catholic University of Korea Bucheon St Mary's Hospital, Bucheon-si, Republic of Korea
  • 8Soonchunhyang University Hospital Bucheon, Bucheon-si, Republic of Korea
  • 9Ulsan University Hospital, Ulsan, Republic of Korea
  • 10Soonchunhyang University Hospital, Yongsan-gu, Republic of Korea
  • 11Myongji Hospital, Goyang-si, Republic of Korea
  • 12Gyeongsang National University College of Medicine, Jinju-si, Republic of Korea
  • 13Inje University Busan Paik Hospital, Busan, Republic of Korea
  • 14Wonkwang University, Iksan-si, Republic of Korea
  • 15Korea University Anam Hospital, Seoul, Republic of Korea
  • 16Kyung Hee University Medical Center, Dongdaemun-gu, Republic of Korea
  • 17Inje University Ilsan Paik Hospital, Goyang-si, Republic of Korea
  • 18Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
  • 19Inje University Haeundae Paik Hospital, Busan, Republic of Korea

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia with poor prognosis. This study evaluated whether monitoring changes in lung function and exercise capacity during antifibrotic therapy offers superior prognostic value compared with baseline clinical parameters in IPF. Methods: We retrospectively analyzed patients with IPF enrolled with the Korean IPF cohort registry between June 2016 and August 2021. Prognostic factors for mortality were assessed using Cox proportional hazards models and receiver operating characteristic (ROC) curve analysis. Results: Among 1,229 patients (mean age 68.3 years; 82.8% male), 88.0% received antifibrotic therapy. During a median follow-up of 41.0 months, 37.9% of the treated patients died. Multivariable Cox analysis revealed that a decline in forced vital capacity (FVC) at 12 months, lower baseline diffusing capacity of the lungs for carbon monoxide (DLco), a decline in DLco at 12 months, and a reduction in the 6-minute walk distance at 6 months, were independent risk factors for mortality in IPF patients receiving antifibrotic therapy. In the ROC curve analysis, the change in FVC at 12 months showed the highest predictive accuracy for mortality (area under the curve = 0.676; p < 0.001). Kaplan–Meier analysis demonstrated significantly poorer survival in patients with ≥5.8% decline in FVC and ≥11.5% decline in DLco over 12 months (p <0.001 and p =0.001, respectively). Conclusions: Longitudinal changes in lung function and exercise capacity as indicators of response to antifibrotic therapy may serve as potential surrogate markers of mortality in patients with IPF.

Keywords: Interstitial Lung Disease, Fibrosis, prognosis, Mortality, Lung function

Received: 04 Aug 2025; Accepted: 24 Sep 2025.

Copyright: © 2025 Oh, Park, Chung, Jeong, Song, Choi, Kim, Park, Jegal, Yoon, Choi, Yoo, Lee, 양, Lee, CHOI, Kang, Park and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jong Sun Park, jspark.im@gmail.com
Jae Ha Lee, anilleus@naver.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material