Lower-limb resistance training reduces exertional dyspnea and intrinsic neuromuscular fatigability in individuals with chronic obstructive pulmonary disease.

Skeletal muscle atrophy, dysfunction, and fatigue are important complications of chronic obstructive pulmonary disease (COPD). Greater reliance on glycolytic metabolism and increased type III/IV muscle afferent activity increase ventilatory drive, promote ventilatory constraint, amplify exertional dyspnea, and limit exercise tolerance. To investigate whether muscular adaptation with resistance training (RT) could improve exertional dyspnea, exercise tolerance, and intrinsic neuromuscular fatigability in individuals with COPD (n = 14, FEV1 = 62 ± 21% predicted), we performed a proof-of-concept single-arm efficacy study utilizing 4 wk of individualized lower-limb RT (3 times/wk). At baseline, dyspnea (Borg scale), ventilatory parameters, lung volumes (inspiratory capacity maneuvers), and exercise time were measured during a constant-load test (CLT) at 75% maximal workload to symptom limitation. On a separate day, fatigability was assessed using 3 min of intermittent stimulation of the quadriceps (initial output of ∼25% maximal voluntary force). Following RT, the CLT and fatigue protocols were repeated. Compared with baseline, isotime dyspnea was reduced (5.9 ± 2.4 vs. 4.5 ± 2.4 Borg units, P = 0.02) and exercise time increased (437 ± 405 s vs. 606 ± 447 s, P < 0.01) following RT. Isotime tidal volume increased (P = 0.01), whereas end-expiratory lung volumes (P = 0.02) and heart rate (P = 0.03) decreased. Quadriceps force, relative to initial force, was higher at the end of the stimulation protocol posttraining (53.2 ± 9.1 vs. 46.8 ± 11.9%, P = 0.04). This study provides evidence that 4 wk of RT attenuates exertional dyspnea and improves exercise tolerance in individuals with COPD, which in part, is likely due to delayed ventilatory constraint and reduced intrinsic fatigability. A pulmonary rehabilitation program beginning with individualized lower-limb RT may help mitigate dyspnea before performing aerobic training in individuals with COPD.NEW & NOTEWORTHY This study presents the novel finding that 4-wk resistance training (RT) focused specifically on the lower limbs can reduce exertional dyspnea during constant-load cycling, improve exercise tolerance, and reduce intrinsic fatigability of the quadriceps in individuals with COPD.

Phenotyping Cardiopulmonary Exercise Limitations in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Exercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes. METHODS: Patients with COPD (n = 95, FEV1:23-113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred). RESULTS: FEV1 varied within phenotype: ventilatory (23-75%pred), combined (28-90%pred), and cardiovascular (68-113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype. CONCLUSION: Distinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.

Cerebrovascular function in patients with chronic obstructive pulmonary disease: the impact of exercise training.

This study examined cerebral blood flow (CBF) and its regulation before and after a short-term periodized aerobic exercise training intervention in patients with chronic obstructive pulmonary disease (COPD). Twenty-eight patients with COPD (forced expiratory volume in 1 s/forced vital capacity < 0.7 and

Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease.

NEW FINDINGS: What is the central question of this study? Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD. What is the main finding and its importance? Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short-term training programmes may not be long enough to improve vascular-related cardiovascular risk in COPD. Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV1 %pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV1 %pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow-mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima-media thickness, carotid compliance, distensibility and ß-stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power (V̇O2 peak ) was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular shear stress. Flow-mediated dilatation was not increased in COPD patients (+0.15 ± 2.27%, P = 0.82) or control subjects (+0.34 ± 3.20%, P = 0.64) and was not different between groups (P = 0.68). No significant improvements in central pulse wave velocity (COPD, +0.30 ± 1.79 m s-1 versus control subjects, -0.34 ± 1.47 m s-1 ) or other markers of vascular structure or function were found within or between groups. The V̇O2 peak increased significantly in COPD and control subjects, and was greater in control subjects (1.6 ± 1.4 versus 4.1 ± 3.7 ml kg min-1 , P = 0.003), while blood pressure and dyspnoea were reduced in COPD patients (P < 0.05). These findings demonstrate that 8 weeks of aerobic training improved cardiorespiratory fitness and blood pressure in COPD but had little effect on other established markers of cardiovascular disease risk.

Ventricular-Arterial Coupling in Breast Cancer Patients After Treatment With Anthracycline-Containing Adjuvant Chemotherapy.

BACKGROUND: Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C. METHODS: Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured. RESULTS: Thirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05). CONCLUSION: In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls. IMPLICATIONS FOR PRACTICE: Anthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.