Mechanisms of activity-related dyspnea in pulmonary diseases

Progressive activity-related dyspnea dominates the clinical presentation of patients afflicted by chronic obstructive and restrictive lung diseases. This symptom invariably leads to activity limitation, global skeletal muscle deconditioning and an impoverished quality of life. The effective management of exertional dyspnea remains an elusive goal but our understanding of the nature and mechanisms of this distressing symptom continues to grow. Refinements in psychophysical measurement of the sensory intensity and quality of dyspnea during laboratory clinical cardiopulmonary exercise testing (CPET) have provided new insights into causation. In this review, we focus on what is known about the physiological mechanisms of dyspnea during physical exertion in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Although these conditions are pathologically diverse, perceptual and ventilatory responses to exercise are remarkably similar among patients with these two conditions. In both patient groups, dyspnea intensity is increased at any given ventilation compared with age-matched healthy individuals; at the limits of tolerance, most patients predominantly select qualitative descriptors that allude to perceptions of “increased respiratory effort” and “unsatisfied inspiration.” Common abnormal physiological responses to CPET across conditions include: (1) increased central respiratory drive secondary to pulmonary gas exchange and metabolic derangements, (2) abnormal “restrictive” constraints on tidal volume expansion with earlier development of critical mechanical limitation of ventilation and (3) an increasing disparity (as exercise proceeds) between the magnitude of contractile respiratory muscle effort and the thoracic volume displacement achieved. Reductionist experimental approaches that attempt to partition, or isolate, the contribution of central and multiple peripheral sensory afferent systems to activity-induced dyspnea have met with limited success. Integrative approaches which explore the possible neurophysiological mechanisms involved in the two dominant qualitative descriptors of activity-related dyspnea in both diseases may prove to be more fruitful. In this review, we present a hypothetical model for exertional dyspnea that is based on current neurophysiological constructs that have been rigorously developed to explain the origins of perceptions of “effort,” “air hunger” and the accompanying affective “distress” response.