Use of 6-min walk distance to predict lung transplant-free survival in fibrosing non-IPF interstitial lung diseases

<bold>Introduction:</bold> Detecting disease progression in patients with fibrosing non-IPF interstitial lung diseases (ILDs) is challenging. We hypothesize that changes in 6-min walk distance (6MWD) from baseline, along with lung function measures, can predict survival and indicate clinically significant progression. <bold>Methods:</bold> Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n=105) and in a validation cohort (n=138) from different centers. The primary endpoint was lung transplant (LTx)-free survival. <bold>Results:</bold> Average follow-up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx-free-survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx-free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC. Discussion: Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression.