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Introduction: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous respiratory disease with important extra-pulmonary features and comorbidities. The aim of this study was to assess clinical heterogeneity in a well-defined subgroup of individuals with COPD GOLD D, including possible gender differences. Methods: Pulmonary function, arterial blood gases, exercise performance, quadriceps muscle function, problematic activities of daily life, dyspnea, health status and comorbidities have been assessed in 117 individuals with a MRC dyspnea grade 4/5 and COPD GOLD D entering pulmonary rehabilitation. Results: A broad range of values were found for diffusion capacity, exercise capacity, quadriceps muscle function and health status. Indeed, the high coefficients of variation were found for these outcomes. Problematic activities of daily life as well as objectified comorbidities also varied to a great extent. Moreover, significant gender differences were found for exercise performance, lower-limb muscle function and various comorbidities. Conclusion: The current findings emphasize that COPD is a heterogeneous disease whose clinical presentation varies significantly, even in individuals with very severe COPD with the same degree of dyspnea and all classified as GOLD D. Trial registration: NTR2322. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The 6-min walk test (6MWT) is used to assess functional capacity in patients with COPD. A significant number of studies have shown that most patients walk further in a second 6MWT. Research on a further increase in the 6-min walk distance (6MWD) during a 3rd test performed in accordance with current guidelines has not been done. Therefore, this study aimed to investigate 1) the reproducibility of three 6MWTs in patients with COPD referred for pulmonary rehabilitation (PR) and 2) predictors of improvement on a third 6MWT., Materials and Methods: Before the start of PR, 1167 COPD patients (50 % male, age: 62 ± 9 years; FEV1: 42 ± 18%pred) performed three 6MWTs (6MWT1, 6MWT2, and 6MWT3). A predetermined threshold of ≥42m improvement in 6MWD in consecutive 6MWT's was used to identify improvers. Reproducibility between tests was assessed using a Bland-Altman plot and logistic regression analyses were performed to assess effects of sex, age, body mass index, GOLD-stage, 6MWD, use of supplemental oxygen and use of walking aids., Results: Generally, the 6MWD improved (6MWT1: 343 ± 115m; 6MWT2: 367 ± 115m; 6MWT3: 381 ± 116m). 210 patients (18 %) improved ≥42m from 6MWT2 to 6MWT3. The Bland-Altman plot showed that the 95 % limits of agreement of 6MWT3 vs 6MWT2 exceeded 42m, indicating that 6MWT2 is not reproducible. Predictors of improvement in 6MWT3 were GOLD stage I/II and a low 6MWD (<350m) in the previous two 6MWTs., Conclusions: These results indicate that three 6MWTs may be required to obtain the largest pre-PR functional capacity in COPD patients. Patients with a 6MWD <350m and GOLD-stage I/II are more likely to improve ≥42m in a third 6MWT., Competing Interests: Declaration of competing interest Jeannet M. Delbressine, Anouk W. Vaes, Wieteke A. M. Stoop, Dirk van Ranst and Alex J. van ’t Hul report no conflict of interest. Martijn A. Spruit reports grants from Lung Foundation Netherlands, Stichting Astma Bestrijding, Boehringer Ingelheim, AstraZeneca, TEVA, Chiesi and Sanofi, and fees from Boehringer Ingelheim, AstraZeneca, TEVA, GSK and Chiesi, all outside the submitted work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)