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Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple “non-invasive” assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions.

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Cardiopulmonary exercise testing (CPET) has traditionally included ventilatory and metabolic measurements alongside electrocardiographic characterization; however, research increasingly acknowledges the utility of also measuring inspiratory neural drive (IND) through its surrogate measure of diaphragmatic electromyography (EMGdi). While true IND also encompasses the activation of non-diaphragmatic respiratory muscles, the current review focuses on diaphragmatic measurements, providing information about additional inspiratory muscle groups for context where appropriate. Evaluation of IND provides mechanistic insight into the origins of dyspnea and exercise limitation across pathologies; yields valuable information reflecting the integration of diverse mechanical, chemical, locomotor, and metabolic afferent signals; and can help assess the efficacy of therapeutic interventions. Further, IND measurement during the physiologic stress of exercise is uniquely poised to reveal the underpinnings of physiologic limitations masked during resting and unloaded breathing, with important information provided not only at peak exercise, but throughout exercise protocols. As our understanding of IND presentation across varying conditions continues to grow and methods for its measurement become more accessible, the translation of these principles into clinical settings is a logical next step in facilitating appropriate and nuanced management tailored to each individual's unique physiology. This review provides an overview of the current state of understanding of IND measurement during CPET: its origins, known patterns of behavior and links with dyspnea in health and major respiratory diseases, and the possibility of expanding this approach to applications beyond exercise.