The current limitations relating to the reference values for CPET either in adults or children are not trivial, and are considered in greater detail in chapters by PUENTE-MAESTU et al. [106] and BURGHARD et al. [107], respectively, elsewhere in this Monograph. In this context, a global frame of reference (akin to the ERS-sponsored Global Lung Initiative for pulmonary function tests [105]) based on a large number of subjects with a broad span of age and body dimensions, and matched for habitual physical activity level, would be particularly useful to enhance test interpretation. This also applies to the interpretation of symptom burden: comprehensive reference intervals for Borg dyspnoea scores as a function of WR [108] and ventilation, for instance, are not yet available. There is a noticeable paucity of normal values for treadmill-based tests. In fact, there is an urgent need to Table 1. Suggested avenues for patient-oriented research in the next 10 years the outcomes of such research may enhance the clinical applicability of CPET in respiratory medicine Investigation of exercise intolerance A global frame of reference for key metabolic, ventilatory and cardiovascular variables in response to standardised cycle ergometer and treadmill protocols Large normative standards for the trajectory of exertional symptoms as a function of exercise intensity (WR) and physiological demands (V′O 2 and V′E) Prospective, multicentre studies addressing the role of CPET in discriminating syndromes of exercise limitation in contemporary clinical populations with multiple co-existing diseases Prospective, multicentre studies testing the incremental role (to commonly used metabolic and ventilatory variables) of noninvasive measurements of lung mechanics and symptoms in the investigation of exertional dyspnoea The clinical value of adding noninvasive to minimally invasive methods to the estimation of stroke volume and PaCO 2 Milder constant load protocols to investigate the mechanisms of exercise intolerance in elderly and frail patients The role of common cardiovascular comorbidities in exertional dyspnoea in COPD and ILD The independent role of diastolic dysfunction, left atrial enlargement, atrial fibrillation and chronotropic incompetence in respiratory symptoms in patients with unexplained dyspnoea CPET-based criteria to differentiate chaotic/erratic breathing patterns from data noise in subjects with suspected dysfunctional breathing hyperventilation Risk assessment CPET variables added to multiparametric models of risk prediction Prognostic assessment of patients with mild/early chronic respiratory disease Risk stratification in chronic respiratory diseases other than COPD Prospective multicentre studies to establish the actual role of CPET in addition to pulmonary function tests and field-based tests in predicting poor outcome after lung resection surgery Addition of the syndromic mechanism of exercise limitation to physiological thresholds in order to improve the prognostic yield of CPET Use of submaximal variables from the incremental test to predict poor outcome Contrasting the predictive values of different metrics of ventilatory inefficiency across disease states Effects of interventions Strategies to optimise the use of constant WR tests to assess the effects of respiratory medication in individual patients Feasible, pragmatic approaches to individualise the exercise intensity for endurance tests Prospective multicentre studies to establish the MCID for changes in time to exercise intolerance in different respiratory diseases Robust criteria to discriminate “responders” from “non-responders” regarding exercise tolerance in clinical trials Submaximal variables from the incremental test to assess the effects of selected interventions xviii https://doi.org/10.1183/2312508X.10015318