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Randomized Controlled Trial
. 2025 Nov 6;66(5):2402565.
doi: 10.1183/13993003.02565-2024. Print 2025 Nov.

Development and validation of a predictive 6-min walk score in patients with idiopathic pulmonary fibrosis

Steven D Nathan  1 , Jie Gao  2 , Ho Cheol Kim  3 , Abhimanyu Chandel  4 , Henry Chen  2 , Xiaomin Lu  2 , Bernt van den Blink  5 , Lixin Shao  2 , Timothy R Watkins  2 , Toby M Maher  6 , Lisa Lancaster  7
Affiliations
Randomized Controlled Trial

Development and validation of a predictive 6-min walk score in patients with idiopathic pulmonary fibrosis

Steven D Nathan et al. Eur Respir J. .

Abstract

Background: The 6-min walk test (6MWT) provides an assessment of patient function and has been employed in interstitial lung disease clinical trials as an end-point. The ISABELA studies were two replicate randomised controlled trials of idiopathic pulmonary fibrosis (IPF) that included a regimented 6MWT protocol. The goal of this study was to combine 6MWT components into a pragmatic, easy to apply, composite clinical prediction score.

Methods: 6MWT parameters associated with time to death or respiratory hospitalisation in the ISABELA studies were integrated into a single composite score. This score was then validated in an external cohort.

Results: There were 1251 patients in the derivation set with 83 respiratory-related hospitalisations and 21 deaths observed after 48 weeks. After multivariable analysis, four parameters were independently predictive of outcomes: Borg dyspnoea score, oxygen flow rate, oxygen saturation nadir and the 6-min walk distance. A pragmatic model, termed the ODDS (oxygen, distance, dyspnoea, saturation) was then developed. This performed better than the individual parameters alone with an area under the curve (AUC) of 0.797, 0.781 and 0.766 for events at 12, 24 and 48 weeks, respectively. The ODDS model was similarly accurate when applied to the external validation set (n=295) at 48 weeks (AUC 0.758, 95% CI 0.688-0.825).

Conclusion: The 6MWT imparts important prognostic information which is best captured by combining constituent variables in a composite score system. The ODDS model might find utility in the clinical setting as well as in IPF studies where it can be used to risk-stratify patients for outcomes.

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Conflict of interest statement

Conflict of interest: S.D. Nathan reports consulting fees from Boehringer Ingelheim, United Therapeutics, Avalyn Pharma, Daewoong, PureTech and Trevi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and United Therapeutics, payment for expert testimony from United Therapeutics, participation on a data safety monitoring board or advisory board with Horizon, AbbVie, Novartis and AstraZeneca, and is a board member of Gossamer Bio. J. Gao is an employee of Gilead Sciences Inc. H. Chen is an employee of Gilead Sciences Inc. X. Lu is an employee of and holds stock (or stock options) in Gilead Sciences Inc. B. van den Blink is a former employee of and has received warrants from Galapagos NV. L. Shao is an employee of and holds stock (or stock options) in Gilead Sciences Inc. T.R. Watkins is an employee of and holds stock (or stock options) in Gilead Sciences Inc. T.M. Maher reports consulting fees from Boehringer Ingelheim, Roche/Genentech, Astra Zeneca, Bayer, Blade Therapeutics, Bristol-Myers Squibb, CSL Behring, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pfizer, Pliant, PureTech, Respivant, Sanofi, Theravance, Trevi, Veracyte and Vicore, participation on a data safety monitoring board or advisory board with Fibrogen, Blade Therapeutics and Nerre, and stock (or stock options) with Qureight. L. Lancaster reports grants from Roche, Pliant, Fibrogen, Boehringer Ingelheim, Novartis, Celgene, Galecto, BMS, Bridge Biotherapeutics, Horizon, CSL Behring, Nerre, Avalyn, DevProBiopharma and PureTech, consulting fees from DevProBiopharma, Pieris, AstraZeneca, Oxygenium, Roche, Bellerophon, Senwha, Daewoong, Daiichi Sankyo, Nashville Biosciences, Veracyte, United Therapeutics, Structure Therapeutics, Fortress Biotech, Tvardi, PureTech, SynDevRx, Avalyn, Abbvie, Boehringer Ingelheim, Grifols, Endeavor, Merus and Aerami, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Genentech, Veracyte and United Therapeutics, patents pending (AutO2), participation on a data safety monitoring board or advisory board with DevProBiopharma, Pieris, Oxygenium, Bellerophon, Veracyte, United Therapeutics, Avalyn, Boehringer Ingelheim, Grifols and Aerami, and stock (or stock options) with Tvardi. The remaining authors declare no competing interests.

Figures

None
Overview of the study. IPF: idiopathic pulmonary fibrosis; 6MWT: 6-min walk test; FVC: forced vital capacity; GAP: gender, age, physiology; 6MWD: 6-min walk distance; SpO2: peripheral oxygen saturation.
FIGURE 1
FIGURE 1
Kaplan–Meier curves of the oxygen flow rate, distance, Borg dyspnoea score and saturation nadir (ODDS) model (stratified by score quartile) to predict time to transplantation or death in the validation cohort.
FIGURE 2
FIGURE 2
Receiver operator characteristic curve (ROC) of the oxygen flow rate, distance, Borg dyspnoea score and saturation nadir (ODDS) model to predict transplant-free survival in the validation set at 1 year. AUC: area under the curve.
See this image and copyright information in PMC

Comment in

References

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