Submaximal eccentric cycling in people with COPD: acute whole-body cardiopulmonary and muscle metabolic responses

BackgroundEccentric cycling (ECC) may be an attractive exercise modality in COPD due to both low cardiorespiratory demand and perception of effort compared to conventional concentric cycling (CON) at matched mechanical loads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to cause sufficient metabolic stress to improve aerobic capacity.Research questionWhat are the cardiopulmonary and metabolic responses to ECC in people with COPD and healthy volunteers when compared to CON at matched mechanical loads?Study Designand Methods: 13 individuals with COPD (mean ± SD age 64 ± 9 years, FEV 1 %pred 45 ± 19%, BMI 24 ± 4 kg.m -2, V̇O 2peak 15 ± 3 ml.kg -1.min -1) and 9 age matched controls (FEV 1 %pred 102 ± 13%, BMI 28 ± 5 kg.m -2, V̇O 2peak 23 ± 5 ml.kg -1.min -1), performed up to six 4 min bouts of ECC and CON at matched mechanical loads of increasing intensity. In addition, 12 individuals with COPD underwent quadriceps muscle biopsies before and after 20 min of ECC and CON at 65% peak power.ResultsAt matched mechanical loads, oxygen uptake, minute ventilation, heart rate, systolic blood pressure, RER (all pInterpretationCardiopulmonary and blood lactate responses during submaximal ECC were less compared to CON at equivalent mechanical workloads in health and COPD, and this was confirmed at a muscle level in COPD. Submaximal ECC was well tolerated and allowed greater mechanical work at lower ventilatory cost. However, in people with COPD, a training intervention based on ECC is unlikely to stimulate cardiovascular and metabolic adaptation to the same extent as CON.</div

Baseline characteristics of the study population by tertile of FEV₁.

<p>Baseline characteristics of the study population by tertile of FEV₁.</p

Effects of lung function on CMR-derived parameters.

<p>Effects of lung function on CMR-derived parameters.</p

Effect sizes for the change in CMR-derived parameter per standard deviation reduction in FEV₁ and FVC, and per one decade increase in age.

<p>Filled shapes represent the change in the CMR-derived parameter per standard deviation reduction in FEV₁ or FVC, or per decade increase in age. Error bars represent the 95% confidence interval for the effect estimate.</p

Case selection flowchart for the primary analysis.

<p>Case selection flowchart for the primary analysis.</p

<i>AGER</i> isoform expression in three HBEC donors using RNA Seq.

<p>Structure and abundance of known <i>AGER</i> isoforms in three human bronchial epithelial cell donors illustrating heterogeneity in expression levels. Percentage abundances (% FPKM) were calculated for each donor. Transcripts for full length and soluble <i>AGER</i> were identified at similar low abundancies. FPKM; fragments per kilobase of transcript per million mapped reads.</p

Immunohistochemical analysis of RAGE expression in healthy and COPD lung.

<p>In healthy lung tissue, RAGE was found to be localised to the cytoplasm and membrane. RAGE expression was high in the pneumocytes of alveolar regions (a). The bronchial epithelium showed variable weak to moderate staining (e). In lung tissue of individuals with COPD, RAGE was very strongly immunopositive in the membrane and cytoplasm of the pneumocytes in the alveolar regions (b). The bronchial epithelium from individuals with COPD was weak or immunonegative for the RAGE protein (f). All isotype controls were negative (c, d, g and h). Representative images of one healthy and one COPD lung shown. x10 magnification.</p

Baseline characteristics of UK smoker population used for genetic association studies.

<p>Baseline characteristics of UK smoker population used for genetic association studies.</p

Gene expression array data of 38 fetal lungs for the <i>AGER</i> probes.

<p>Expression intensities for the <i>AGER</i> probes 210081_at and 217046_s_at were plotted against the gestational age of each fetal lung sample and showed an increase in expression with fetal lung age. RMA; Robust Multi-array Average. Affymetrix U133 Plus 2 expression array probe 210081_at probes for exon 8 of AGER mRNA whilst 217046_s_at probes AGER exons 7–11’.</p

Fetal lung gene array data for <i>AGER</i> expression across Pseudoglandular and Canalicular stages.

<p>Fetal lung gene array data for <i>AGER</i> expression across Pseudoglandular and Canalicular stages.</p