Denis E. O’Donnell

Linda Nici, Claudio Donner, Emiel Wouters, Richard Zuwallack, Nicolino Ambrosino, Jean Bourbeau, Mauro Carone, Bartolome Celli, Marielle Engelen, Bonnie Fahy, Chris Garvey, Roger Goldstein, Rik Gosselink, Suzanne Lareau, Neil MacIntyre, Francois Maltais, Mike Morgan, Denis O’Donnell, Christian Prefault, Jane Reardon, Carolyn Rochester, Annemie Schols, Sally Singh, and Thierry Troosters, on behalf of the ATS/ERS Pulmonary Rehabilitation Writing Committee

BACKGROUND: Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular diseases. Since the ATS published a consensus statement on dyspnea in 1999, there has been enormous growth in knowledge about the neurophysiology of dyspnea and increasing interest in dyspnea as a patient-reported outcome. PURPOSE: The purpose of this document is to update the 1999 ATS Consensus Statement on dyspnea. METHODS: An interdisciplinary committee of experts representing ATS assemblies on Nursing, Clinical Problems, Sleep and Respiratory Neurobiology, Pulmonary Rehabilitation, and Behavioral Science determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant expertise. The final content of this statement was agreed upon by all members. RESULTS: Progress has been made in clarifying mechanisms underlying several qualitatively and mechanistically distinct breathing sensations. Brain imaging studies have consistently shown dyspnea stimuli to be correlated with activation of cortico-limbic areas involved with interoception and nociception. Endogenous and exogenous opioids may modulate perception of dyspnea. Instruments for measuring dyspnea are often poorly characterized; a framework is proposed for more consistent identification of measurement domains. CONCLUSIONS: Progress in treatment of dyspnea has not matched progress in elucidating underlying mechanisms. There is a critical need for interdisciplinary translational research to connect dyspnea mechanisms with clinical treatment and to validate dyspnea measures as patient-reported outcomes for clinical trials.

The role of dynamic hyperinflation (DH) in exercise limitation in chronic obstructive pulmonary disease (COPD) remains to be defined. We examined DH during exercise in 105 patients with COPD (FEV(1) = 37 +/- 13% predicted; mean +/- SD) and studied the relationships between resting lung volumes, DH during exercise, and peak oxygen consumption (VO(2)). Patients completed pulmonary function tests and incremental cycle exercise tests. We measured the change in inspiratory capacity (Delta IC) during exercise to reflect changes in DH. During exercise, 80% of patients showed significant DH above resting values. IC decreased 0.37 +/- 0.39 L or 14 +/- 15% predicted during exercise (p < 0.0005), but with large variation in range. Delta IC correlated best with resting IC, both expressed %predicted (r = -0.50, p < 0.0005). Peak VO(2) (%predicted maximum) correlated best with the peak tidal volume attained (VT standardized as % of predicted vital capacity) (r = 0.68, p < 0.0005), which, in turn, correlated strongly with IC at peak exercise (r = 0.79, p < 0.0005) or at rest (r = 0.75, p < 0.0005). The extent of DH during exercise in COPD correlated best with resting IC. DH curtailed the VT response to exercise. This inability to expand VT in response to increasing metabolic demand contributed importantly to exercise intolerance in COPD.

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest. For symptom-limited incremental exercise, CPET indices, such as peak O(2) uptake (V'O(2)), V'O(2) at lactate threshold, the slope of the ventilation-CO(2) output relationship and the presence of arterial O(2) desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g. timed and shuttle walking tests) also prove valuable. In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) "When should an evaluation of exercise intolerance be sought?"; 2) "Which particular form of test should be asked for?"; and 3) "What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?"