ECSS Paris 2023: OP-MH13
INTRODUCTION: Background: Pulmonary ventilatory and peripheral muscle dysfunction often prevent patients with chronic obstructive pulmonary disease (COPD) from tolerating high-intensity exercise required to improve muscle strength. Additionally, COPD patients frequently suffer from systemic inflammation, leading to exercise intolerance and ultimately a decline in health-related quality of life. Eccentric cycling allows high mechanical loading at a relatively low metabolic/cardiopulmonary cost and may therefore represent a feasible alternative training modality for patients with COPD. Objective: This study investigated the effects of intelligent eccentric cycling training on cardiopulmonary/muscular fitness, functional performance, and peripheral blood immune markers in patients with COPD. METHODS: Participants (n=26) were randomly assigned to either the training group (n=14) or the control group (n=12). The training group completed a 12-week intelligent eccentric cycling training program, which included a 2-week adaptation period and a 10-week formal training period, with exercise intensity gradually increasing from 80% to 160% of peak workload (Wpeak). The control group received general healthcare and maintained their daily activities. Measurements were taken at baseline, during the control period, and after the intervention, including cardiopulmonary exercise test, timed up and go test (TUG), 6-minute walk test (6MWT), isokinetic strength test, and hematological/immunological parameters. RESULTS: Before the intervention, there were no significant differences in cardiopulmonary exercise variables, isokinetic muscle performance, and hematological/immunological parameters between the training and control groups. Eccentric cycling training for 10 weeks (i) increased the distance of 6MWT, (ii) improved TUG performance, (iii) increased relative work at 60°/sec and 180°/sec during knee extension, (iv) lowered the muscular fatigue index of knee extension, and (v) reduced neutrophil count and the ratio of CD4 to CD8 cells in the training group. However, no significant changes in cardiopulmonary/muscular fitness and hematological/immunological parameters after 12-week general healthcare in the control group. CONCLUSION: The intelligent eccentric cycling regimen effectively improves cardiopulmonary/muscular fitness, functional performance, and immune regulation, providing a clinically feasible training strategy for pulmonary rehabilitation in COPD.
Read CV Hui Wen HsuECSS Paris 2023: OP-MH13
INTRODUCTION: Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD) and is only partially explained by respiratory limitations. Skeletal muscle dysfunction, comprehending mitochondrial impairment, may represent a key determinant of reduced functional capacity. However, the contribution of mitochondrial dysfunction in skeletal muscles to exercise intolerance in COPD remains insufficiently characterized. METHODS: Fourteen COPD patients (7 females and 7 males; age 67±8 years and body mass 70±17 kg) with moderate-to-severe airflow obstruction (forced expiratory volume in one second, FEV1= 50.4±7.9 %predicted) and 31 healthy controls (CTRL) were recruited; 7 participants per group underwent vastus lateralis muscle biopsy. Exercise tolerance was assessed by cardiopulmonary exercise testing performed on a cycle ergometer to determine peak pulmonary oxygen uptake (V̇O2peak). Skeletal muscle oxidative metabolism was evaluated ex vivo using high-resolution respirometry (HRR) in permeabilized skeletal muscle fibers. Leak respiration (LEAK), maximal ADP-stimulated mitochondrial respiration (OXPHOS) and ADP sensitivity (apparent Km) were assessed in duplicate in experimental conditions of unlimited O2 availability. Markers of mitochondrial content were assessed, including citrate synthase (CS) expression and activity, skeletal muscle fiber-type composition (myosin heavy chain isoforms) and capillary density were determined. RESULTS: V̇O2peak was markedly reduced in COPD compared to CTRL (16.4±3.0 vs. 29.9±5.7 ml·kg⁻¹·min⁻¹; p< 0.05). Ex vivo mitochondrial respiration assessed by HRR showed no differences between groups. In COPD, LEAK (12±4 pmol·s⁻¹·mg⁻¹) and OXPHOS (41±13 pmol·s⁻¹·mg⁻¹) respirations were similar to the values in CTRL (14±4 and 40±14, respectively; p>0.05). Apparent ADP sensitivity tended to be higher (lower apparent Km) in COPD compared to CTRL (+28%; p=0.15). Markers of mitochondrial content (CS) were not different between groups (p>0.05). In contrast, COPD patients exhibited a higher proportion of type IIa muscle fibers (Δ=+25%; p< 0.01) and a reduced capillary density (-25%; p=0.01) vs. CTRL. CONCLUSION: COPD patients exhibited markedly reduced exercise tolerance despite preserved mitochondrial mass and respiratory capacity, as evidenced by preserved CS expression and activity and preserved mitochondrial respiration. These findings suggest that exercise intolerance in COPD is unlikely to be driven by mitochondrial respiratory dysfunction, but rather by altered muscle O2 delivery, including changes in fiber-type composition and reduced capillary density. Importantly, because intrinsic mitochondrial function seems to be preserved, interventions aimed at improving “upstream” determinants of O2 delivery -such as respiratory, cardiovascular and microvascular functions, muscle perfusion, capillarization, peripheral O2 diffusion - may effectively enhance exercise tolerance in COPD patients. Funding: MUR PRIN Project 2022, P2022XX7YL.
Read CV Lucrezia ZuccarelliECSS Paris 2023: OP-MH13
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by impaired gas exchange resulting from ventilation to perfusion (VA/Q) heterogeneity. Increased physiological dead space (VD/VT) is responsible for wasted ventilation, reduced ventilatory efficiency, and VA/Q heterogeneity, which may amplify the alveolar–arterial PO2 gradient (A–a O₂ diff), potentially leading to frank hypoxemia. These indices describe distinct components of gas-exchange dysfunction that may differentially contribute to ventilatory inefficiency, hypercapnia, and impaired exercise performance. This study aimed to investigate the relationship between ventilatory efficiency, VD/VT, and A–a O₂ diff at rest and during incremental cardiopulmonary exercise testing (CPET) in patients with COPD. METHODS: 14 patients (7 women, 7 men; 66±8 yy; 70±17 kg) with moderate-to-severe COPD (GOLD II–III, FEV₁ ≤50% predicted) and thirty-one age-matched healthy controls performed an incremental cycle-ergometer CPET. Ventilatory efficiency was assessed using VE/VCO₂ slope, intercept and nadir. In a subgroup of seven COPD patients and fourteen controls, physiological dead space (VD/VT) was estimated non-invasively using transcutaneous PCO₂ (1) and a mass-balance approach (2). The alveolar–arterial oxygen gradient was calculated from arterialized capillary blood gas analysis obtained at rest and peak exercise (3). Group differences were analysed using unpaired t-tests with Welch’s correction. RESULTS: The VE/VCO₂ slope did not differ between COPD and controls, whereas the VE/VCO₂ intercept was significantly higher in COPD (6.5 ± 1.9 vs 4.0 ± 2.4 L·min⁻¹, p = 0.001). The VE/VCO₂ nadir was also significantly higher in COPD compared with controls (36.0 ± 7.9 vs 28.4 ± 3.3, p = 0.003). Arterial O₂ saturation was lower in COPD than in controls at rest and peak exercise (both p<0.001) but remained above 90%. VD/VT was consistently elevated in COPD from rest to peak exercise (≈ +32% vs controls, p < 0.05), indicating increased wasted ventilation. A–a O₂ diff was significantly higher in COPD at rest and peak exercise (≈ +60% vs controls, p < 0.01) but did not parallel changes in ventilatory efficiency indices. CONCLUSION: During incremental exercise in COPD, ventilatory inefficiency is primarily associated with increased VD rather than impaired oxygenation. The dissociation between ventilatory efficiency indices and A–a O₂ diff suggests that wasted ventilation is a dominant contributor to ventilatory inefficiency during exercise. These findings support the use of non-invasive physiological markers to characterize exercise gas-exchange abnormalities in COPD. Funding: MUR PRIN Project 2022, P2022XX7YL. REFERENCES: 1. Cao M, et al. COPD. 2021 Feb; 18(1):16 - 25. 2. Whipp BJ, Ward SA. Br J Sports Med. 1998 Sep;32(3):199 – 211 3. Rahn, H., & Fenn, W. O. (1955). A graphical analysis of the respiratory gas exchange: The O2-CO2 diagram. American Physiological Society.
Read CV Alice GaspariniECSS Paris 2023: OP-MH13