Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD

Abstract

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 +/- 3%predicted; mean +/- SE) inhaled tiotropium 18 mug or placebo once daily for 7-10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 +/- 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.

Mechanisms to dyspnoea and dynamic hyperinflation related exercise intolerance in COPD

“…1) (28). Dyspnoea manifestation is often associated with dynamic hyperinflation (DH) in patients with COPD from moderate to severe obstruction (26,28,29,35,42). The discrepancy between respiratory centre induced respiratory muscle work and muscle load, and capacity related lung volume changes lead to neuromechanical dissociation (Fig.…”

Lung hyperinflation in COPD: the impact of pharmacotherapy

“…Altered peripheral sensory inputs from these sources, together with reduced central corollary discharge, culminate in reduced perceived respiratory discomfort during physical exertion in ways that are not yet fully understood. Although the precise mechanisms remain to be elucidated, the emerging evidence supports the idea that the salutary effects of BDs on respiratory sensation in COPD patients are ultimately linked to enhanced neuromechanical coupling of the respiratory system as a result of improved dynamic ventilatory mechanics [12].…”

“…In one study, treatment with the long-acting anticholinergic agent, tiotropium, was associated with consistent reductions in the ratio of respiratory effort to volume displacement throughout exercise, suggesting a more harmonious relation between neural drive and the mechanical response ( fig. 4) [12]. BD-induced unloading of the ventilatory muscles must mean that less neural activation is required for a given force generation.…”

“…A recent mechanical study on the mechanisms of dyspnoea relief following tiotropium therapy showed that release of cholinergic tone was associated with improved airway conductance at all lung volumes, from total lung capacity to RV [12]. Static elastic recoil of the lung was unchanged after acutely administered tiotropium and expiratory timing during spontaneous resting breathing was unaffected.…”

“…Several studies, which used various BDs, have now shown that increased IC both at rest and during exercise is associated with increased tidal volume (VT) and ventilatory capacity [3][4][5][16][17][18][19][20]. Greater VT expansion is accompanied by reduced breathing frequency throughout exercise, which, in turn, results in increased dynamic lung compliance [12]. Moreover, reduced airways resistance, together with reduced inspiratory threshold and elastic loading of the inspiratory muscles, means that a lower inspiratory effort is now required for a given ventilation.…”