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Peer-reviewedCC BY-NCERJ open research

6-min walk test reveals early physiological impairment in fibrotic interstitial lung diseases

  • Takashi Ogura1
  • Ryo Okuda1
  • Ichiro Kuwahira2
  • Hirotaka Nishikiori3
  • Hirofumi Chiba3
  • Yuriko Takeda4
  • Takafumi Suda5
  • Tomoyuki Fujisawa5
  • Mitsuhiro Abe6
  • Hiromi Tomioka7
  • Susumu Sakamoto8
  • Yoshiaki Zaizen9
23 more authors
  • Hirotsugu Ohkubo10
  • Hiroyoshi Yamauchi11
  • Tetsuji Kawamura12
  • Masahiro Kimura13
  • Koji Sakamoto14
  • Yasuhiko Koga15
  • Osamu Nishiyama16
  • Hiroaki Nakagawa17
  • Kazuhiro Yatera18
  • Kazuhiro Usui19
  • Hidekazu Matsushima20
  • Dai Hashimoto21
  • Tomohiro Handa22
  • Tomoo Kishaba23
  • Hidenori Ichiyasu24
  • Yoshitaka Oyamada25
  • Toshiaki Matsuda26
  • Hiroshi Ishimoto27
  • Osamu Narumoto28
  • Toshihiro Nukiwa29
  • Kunihiko Kobayashi30
  • JIPS Registry collaborators
  • JIPS Registry collaborators
30 affiliations
  1. 1Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
  2. 2Respiratory Disease Center, Tokyo General Hospital, Tokyo, Japan.
  3. 3Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
  4. 4Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan.
  5. 5Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  6. 6Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  7. 7Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan.
  8. 8Department of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.
  9. 9Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
  10. 10Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  11. 11Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
  12. 12Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center, Himeji, Japan.
  13. 13Department of Respiratory Medicine, National Hospital Organization Matsue Medical Center, Matsue, Japan.
  14. 14Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  15. 15Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
  16. 16Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Sakai, Japan.
  17. 17Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
  18. 18Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Kitakyusyu, Japan.
  19. 19Department of Respiratory Medicine, NTT Medical Center Tokyo, Tokyo, Japan.
  20. 20Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan.
  21. 21Respiratiory Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
  22. 22Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  23. 23Department of Respiratory Medicine, Okinawa Chubu Hospital, Uruma, Japan.
  24. 24Department of Respiratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
  25. 25Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
  26. 26Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  27. 27Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  28. 28National Hospital Organization Tokyo National Hospital, Kiyose, Japan.
  29. 29Tohoku University, Sendai, Japan.
  30. 30Department of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Japan.
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Abstract

Rationale

Early prediction of lung function decline remains challenging in idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILDs). We evaluated whether oxygen desaturation during the 6-min walk test (6MWT) predicts forced vital capacity (FVC) decline and long-term outcomes.Methods

We analysed data from two independent cohorts: the nationwide Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry and an external IPF cohort (K-Junko Study). Hazard ratios (HRs) were estimated for each 6MWT parameter to identify variables associated with FVC decline and to determine optimal thresholds. Sensitivity analyses were conducted using Fine-Gray models. The performance of the predictive model was assessed using calibration plots and the concordance index (C-index).Results

In the JIPS IPF (n=457) and K-Junko IPF (n=318) cohorts, a peripheral oxygen saturation (S pO₂ ) change of ≤-6 percentage points during the 6MWT independently predicted a decline in FVC of ≥5 percentage points in both cohorts (JIPS HR 1.292; K-Junko HR 1.480). Moreover, S pO₂ change during the 6MWT was significantly associated with FVC change in the subsequent year, and this association persisted over 5 consecutive years in JIPS IPF cohort. The nomogram demonstrated moderate discrimination (C-index: 0.619 (training) and 0.632 (validation)) and fair calibration. A composite profile meeting all three criteria (FVC ≥80%, S pO₂ change >-6 percentage points, 6-min walk distance (6MWD) ≥420 m) identified patients with favourable transplant-free survival. In the JIPS non-IPF fibrotic ILD cohort (n=387), S pO₂ change remained the sole independent predictor of an FVC decline of ≥5 percentage points (HR 1.350).Conclusion

S pO₂ change during the 6MWT predicts FVC decline and outcomes across fibrotic ILD; its incorporation into routine assessment may enable earlier risk stratification and facilitate timely intervention.

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Cite

BibTeXRIS
BibTeX
@article{ogura20266min,
  title = {{6-min walk test reveals early physiological impairment in fibrotic interstitial lung diseases}},
  author = {Takashi Ogura and Ryo Okuda and Ichiro Kuwahira and Hirotaka Nishikiori and Hirofumi Chiba and Yuriko Takeda and Takafumi Suda and Tomoyuki Fujisawa and Mitsuhiro Abe and Hiromi Tomioka and Susumu Sakamoto and Yoshiaki Zaizen and Hirotsugu Ohkubo and Hiroyoshi Yamauchi and Tetsuji Kawamura and Masahiro Kimura and Koji Sakamoto and Yasuhiko Koga and Osamu Nishiyama and Hiroaki Nakagawa and Kazuhiro Yatera and Kazuhiro Usui and Hidekazu Matsushima and Dai Hashimoto and Tomohiro Handa and Tomoo Kishaba and Hidenori Ichiyasu and Yoshitaka Oyamada and Toshiaki Matsuda and Hiroshi Ishimoto and Osamu Narumoto and Toshihiro Nukiwa and Kunihiko Kobayashi and JIPS Registry collaborators and JIPS Registry collaborators},
  journal = {ERJ open research},
  year = {2026},
  month = nov,
  doi = {10.1183/23120541.00691-2026},
  url = {https://europepmc.org/article/PMC/PMC13725836},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - 6-min walk test reveals early physiological impairment in fibrotic interstitial lung diseases
AU  - Takashi Ogura
AU  - Ryo Okuda
AU  - Ichiro Kuwahira
AU  - Hirotaka Nishikiori
AU  - Hirofumi Chiba
AU  - Yuriko Takeda
AU  - Takafumi Suda
AU  - Tomoyuki Fujisawa
AU  - Mitsuhiro Abe
AU  - Hiromi Tomioka
AU  - Susumu Sakamoto
AU  - Yoshiaki Zaizen
AU  - Hirotsugu Ohkubo
AU  - Hiroyoshi Yamauchi
AU  - Tetsuji Kawamura
AU  - Masahiro Kimura
AU  - Koji Sakamoto
AU  - Yasuhiko Koga
AU  - Osamu Nishiyama
AU  - Hiroaki Nakagawa
AU  - Kazuhiro Yatera
AU  - Kazuhiro Usui
AU  - Hidekazu Matsushima
AU  - Dai Hashimoto
AU  - Tomohiro Handa
AU  - Tomoo Kishaba
AU  - Hidenori Ichiyasu
AU  - Yoshitaka Oyamada
AU  - Toshiaki Matsuda
AU  - Hiroshi Ishimoto
AU  - Osamu Narumoto
AU  - Toshihiro Nukiwa
AU  - Kunihiko Kobayashi
AU  - JIPS Registry collaborators
AU  - JIPS Registry collaborators
PY  - 2026
DA  - 2026/11/01
JO  - ERJ open research
DO  - 10.1183/23120541.00691-2026
UR  - https://europepmc.org/article/PMC/PMC13725836
AB  - Rationale  Early prediction of lung function decline remains challenging in idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILDs). We evaluated whether oxygen desaturation during the 6-min walk test (6MWT) predicts forced vital capacity (FVC) decline and long-term outcomes.Methods  We analysed data from two independent cohorts: the nationwide Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry and an external IPF cohort (K-Junko Study). Hazard ratios (HRs) were estimated for each 6MWT parameter to identify variables associated with FVC decline and to determine optimal thresholds. Sensitivity analyses were conducted using Fine-Gray models. The performance of the predictive model was assessed using calibration plots and the concordance index (C-index).Results  In the JIPS IPF (n=457) and K-Junko IPF (n=318) cohorts, a peripheral oxygen saturation (S pO₂ ) change of ≤-6 percentage points during the 6MWT independently predicted a decline in FVC of ≥5 percentage points in both cohorts (JIPS HR 1.292; K-Junko HR 1.480). Moreover, S pO₂ change during the 6MWT was significantly associated with FVC change in the subsequent year, and this association persisted over 5 consecutive years in JIPS IPF cohort. The nomogram demonstrated moderate discrimination (C-index: 0.619 (training) and 0.632 (validation)) and fair calibration. A composite profile meeting all three criteria (FVC ≥80%, S pO₂ change >-6 percentage points, 6-min walk distance (6MWD) ≥420 m) identified patients with favourable transplant-free survival. In the JIPS non-IPF fibrotic ILD cohort (n=387), S pO₂ change remained the sole independent predictor of an FVC decline of ≥5 percentage points (HR 1.350).Conclusion  S pO₂ change during the 6MWT predicts FVC decline and outcomes across fibrotic ILD; its incorporation into routine assessment may enable earlier risk stratification and facilitate timely intervention.
SN  - 2312-0541
ER  -