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Supplemental material, Reviewer_1_v.1 for Relieving exertional dyspnea during the 3-min constant speed shuttle test in patients with COPD with indacaterol/glycopyrronium versus tiotropium: the RED trial by Jessie Beaulieu, Dennis Jensen, Denis E. O’Donnell, Cynthia Brouillard, Lauren Tracey, Sandra Vincent, Éric Nadreau, Emmanuelle Bernard, Sarah Bernard and François Maltais in Therapeutic Advances in Respiratory Disease

PURPOSE OF REVIEW: Exertional breathlessness is common and pervasive across various chronic disease populations. To accurately assess response to intervention and optimize clinical (symptom) management, detailed assessment of exertional breathlessness is imperative. This review provides an update on current approaches to assess exertional breathlessness and presents the need for individualized assessment of breathlessness standardized for the level of exertion. RECENT FINDINGS: Breathlessness assessment tools commonly invite people to recall their breathlessness while at rest with reference to activities of daily living. To directly quantify breathlessness, however, requires assessment of the dimensions of breathlessness (e.g., sensory intensity, quality, and unpleasantness) in response to a standardized exercise stimulus. Different exercise stimuli (e.g., self-paced, incremental, and constant work rate exercise tests) have been used to elicit a breathlessness response. Self-paced (e.g., 6-min walk test) and incremental exercise tests assess exercise tolerance or endurance, and are not recommended for assessment of exertional breathlessness. Constant work rate tests, however, including recently validated 3-min constant-rate stair stepping and walking tests, standardize the exercise stimulus to enable the breathlessness response to be directly quantified and monitored over time. SUMMARY: To adequately guide symptom management and assess intervention efficacy, clinicians and researchers should assess breathlessness with multidimensional assessment tools in response to a standardized and individualized exercise stimulus. Refereed/Peer-reviewed

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with pulmonary and extra-pulmonary factors contributing to exercise intolerance. The primary self-reported exercise-limiting symptom may reflect the primary pathophysiological factor contributing to exercise intolerance. We compared physiological and perceptual responses at the symptom-limited peak of incremental cardiopulmonary cycle exercise testing between people with COPD reporting breathlessness (B, n = 34), leg discomfort (LD, n = 16), or a combination of B and LD (BOTH, n = 42) as their main exercise-limiting symptom(s). Despite similarly impaired health status, symptomology and peak exercise capacity, the B group had greater restrictive constraints on tidal volume expansion at end-exercise and was more likely to report unpleasant qualities of exertional breathlessness than LD and BOTH groups. In conclusion, reporting breathlessness as the primary exercise-limiting symptom indicated the presence of distinct lung pathophysiology and symptom perception during exercise in people with COPD. Refereed/Peer-reviewed