Development of a Predictive 6 Minute Walk Score in Patients With Idiopathic Pulmonary Fibrosis

Abstract Introduction: The six minute walk test (6MWT) provides a functional assessment and has been employed in many trials as an endpoint. The ISABELA studies were two large replicate IPF studies that included a regimented 6MWT protocol with multiple variables recorded. Objective: To assess the predictive ability of 6MWT parameters with time to respiratory hospitalization or death as the outcome measure and to combine the predictive variables in one composite score. Methods: The standardized 6MWT comprised clear guidance on test conditions with key assessments including amount of supplemental oxygen, 6MWT distance, distance walked at 1 and 3 minutes, Borg dyspnea score, heart rate, heart rate recovery, blood pressure, and oxygen desaturation levels. Results: There were 1251 IPF patients with evaluable data and a baseline median 6MWT of 405 meters (interquartile range: 331 to 474). There were 124 respiratory-related hospitalizations and 34 deaths by 52 weeks. After multivariable analysis, four parameters were independently predictive of outcomes; Borg dyspnea score, oxygen flow rate, oxygen saturation nadir and the 6MWT distance. A pragmatic model, termed the ODDS (oxygen, distance, dyspnea, saturation) was developed with weighting of the parameters as follows: Borg score 2-5=3; Borg>5=19; oxygen flow rate 3-6L/min=28; 6MWT 350-450=15; 300-350=26;<300=34; SpO2nadr<90%=19. The baseline ODDS score (maximum of 100) performed better than the individual parameters with an area under the curve of 0.797, 0.781 and 0.766 for events at 12,24 and 48 weeks, respectively. Table. Number (%) patients with death or hospitalization at 12,24 and 48 weeks by baseline ODDS score in tertiles Conclusions: The 6MWT imparts important prognostic information in IPF patients which is best captured by combining constituent variables in a composite score system. The ODDS composite has the benefit of incorporating how patients feel (Borg dyspnea score) while they function (walk). 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 and potentially employed as a trial endpoint.