Prediction of Poor Short-Term Prognosis and Unmet Needs in Advanced Chronic Obstructive Pulmonary Disease: Use of the Two-Minute Walking Distance Extracted from a Six-Minute Walk Test

Abstract

Objectives: Prognostic challenges hinder the identification of patients with advanced chronic obstructive pulmonary disease (COPD) for timely palliative interventions. We postulate that a two-minute derivative (two-minute walking distance [2MWD]) of a standard six-minute walk test (6MWT) can identify frail subjects with poorer survival for early palliative intervention. The primary outcome of interest is mortality at 18 months. Secondary objectives include evaluation of the relationship between the 2MWD and ability to self-care, dyspnea-related disabilities, nutrition, forced expiratory volume in first second (FEV₁), quality of life (QoL), and comorbidity burden.

Design and setting: One hundred twenty-four subjects with stage 3 and 4 COPD were recruited and followed up. Ability to self-care, dyspnea-related disabilities, airflow limitation, nutrition, and QoL were measured by using modified Barthel index (MBI), Modified Medical Research Council (MMRC) dyspnea scale, FEV₁ (% predicted), BODE [BMI(B), FEV₁(O), MMRC(D), 6MWT(E)] index, updated ADO [Age(A), MMRC(D), FEV₁(O)] index, Subjective Global Assessment (SGA), and St. George's Respiratory Questionnaire (SGRQ), respectively. Survival data were prospectively collected and analyzed.

Results: The 2MWD correlates highly with BODE and predicts updated ADO independent of age, co-morbidities, long-term oxygen therapy (LTOT), body mass index, and FEV₁. Log-rank test performed with Kaplan-Meier plots demonstrates that 2MWD ≤80 m significantly predicts survival time (p < 0.05). Cox proportional hazard regression shows a 3.6-time greater probability of 18-month mortality (hazard ratio [HR] 3.57; 95% confidence interval [CI] 1.26-10.13; p < 0.05). In addition, 2MWD strongly predicted MBI and MMRC, independent of age, co-morbidities, LTOT, body mass index, and FEV₁. Subjects with 2MWD ≤80 m have a poorer ability to self-care (median MBI 90 vs. 100), lower FEV₁ (32.9% ± 9.8% vs. 38.1% ± 9.4%), poorer QoL (mean SGRQ 46.6 ± 16.2 vs. 36.6 ± 13.3), and greater dyspnea-related disability (mean MMRC 1.7 ± 0.7 vs. 0.9 ± 0.6), and they are more malnourished (40.4% vs. 9.7%; RR 1.51) (all p < 0.001).

Conclusion: 2MWD ≤80 m identifies subjects with higher mortality, greater functional dependence, poorer in nutrition, greater dyspnea, and lower QoL. Incorporation of 2MWD into composite prognostic indices can enhance predictive accuracy and identify patients requiring early proactive palliative interventions.

Keywords: chronic obstructive pulmonary disease; mortality; palliative care; walking test.