Manoj K. Menon

Ultrasound assessment of lower limb muscle mass in response to resistance training in COPD

BackgroundQuantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD. Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT. We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT.MethodsPortable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT. Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt). Thigh lean mass (Tdexa) was determined by DEXA.ResultsTraining resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively]. The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT.ConclusionsSerial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD. The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA.Trial registrationhttp://www.controlled-trials.com (Identifier: ISRCTN22764439)

Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD

Background Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood. Methods Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT. Results 59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (∼5%) and strength (∼20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT. Conclusions The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.

Inflammatory and Satellite Cells in the Quadriceps of Patients With COPD and Response to Resistance Training

BACKGROUND Quadriceps dysfunction in COPD may be mediated by inflammatory mechanisms or impaired satellite cell function. Resistance training is of proven efficacy in these patients, but data on muscle inflammatory and satellite cell response to resistance exercise in COPD are lacking.We aimed to examine the inflammatory and satellite cell profile of the quadriceps in patients with COPD and healthy control subjects at rest and after acute and chronic resistance exercise. METHODS Seventeen patients with COPD and 10 healthy control subjects underwent 8 weeks ofbilateral lower-limb, high-intensity resistance training, thrice weekly, on an isokinetic dynamometer.Quadriceps muscle biopsy specimens from the dominant thigh were obtained at baseline,24 h following the fi rst exercise bout, and after 8 weeks 24 h after the last exercise bout. Glycolmethacrylate-embedded muscle biopsy specimens were analyzed using immunohistochemistry to identify neutrophils, macrophages, and satellite cells. RESULTS Neutrophils were significantly elevated in the quadriceps of patients with COPD at baseline compared with healthy control subjects ( P 5 .03). Inflammatory cells were increased significantly at 24 h in both groups but were similar to baseline values at week 8, with no difference detectable between healthy control subjects and patients with COPD. Satellite cell numbers were comparable between patients and control subjects at baseline, tended to increase at 24 h, and remained elevated at week 8. CONCLUSIONS Inflammatory cells are elevated in the resting quadriceps of patients with COPD. Acute resistance exercise leads to an inflammatory myositis, which is attenuated with regular training. Satellite cells in patients and control subjects are comparable and are increased in response to exercise. TRIAL REGISTRY ISRCTN Register ; No.: ISRCTN22764439; URL: www.controlled-trials.com.

Ventilatory requirements of quadriceps resistance training in people with COPD and healthy controls.

Background It is proposed that resistance training (RT) does not activate the cardiopulmonary system to the same extent as whole-body exercise. This is important for patients with chronic obstructive pulmonary disease (COPD) who are ventilatory limited. Objective The aim was to assess the ventilatory response to an isokinetic quadriceps RT program in people with COPD and healthy controls. Design Observational. Registration number ISRCTN22764439. Setting Outpatient, university teaching hospital. Participants and outcome measures People with COPD (n=14) and healthy controls (n=11) underwent breath-by-breath analysis of their ventilation during an RT session (five sets of 30 maximal knee extensions at 180°/sec). Subjects performed a maximal cycle ergometry test (CET) at baseline. Peak ventilation (VE; L/min) and oxygen consumption (VO2; mL/kg/min) were collected. The same system measured VO2 and VE during the RT session. Parameters are presented as a percentage of the maximal CET. Isokinetic workload, symptom scores, heart rate (HR), and oxygen saturation were documented post-training. Results People with COPD worked at higher percentages of their maximal capacity than controls (mean range between sets 1–5 for VO2 =49.1%–60.1% [COPD], 45.7%–51.43% [controls] and for VE =57.6%–72.2% [COPD], 49.8%–63.6% [controls]), although this was not statistically significant (P>0.1 in all cases). In absolute terms, the difference between groups was only significant for actual VO2 on set 2 (P<0.05). Controls performed more isokinetic work than patients with COPD (P<0.05). Median Borg symptom scores after RT were the same in both groups (3 breathlessness, 13 exertion), no de-saturation occurred, and both groups were training at ≥65% of their maximum HR. Conclusion No statistically significant differences were found between people with COPD and healthy controls for VO2 and VE achieved during training. The symptoms associated with training were within acceptable limits.

Respiratory Considerations and Effect of Bariatric Surgery in the Obese Patient

Pulmonary function abnormalities are quite common in obesity. Consequently, in this population, a number of respiratory comorbidities are seen, which have to be identified and treated prior to bariatric surgery. The most commonly occurring conditions are obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), pulmonary hypertension and asthma. Preoperative assessment includes a detailed history and clinical examination, followed by appropriate investigations to detect these comorbidities. OSA is highly prevalent in the population undergoing bariatric surgery and should be considered in all patients during the preoperative evaluation. Screening tools and questionnaires are useful to identify patients with OSA, although there are suggestions that all patients presenting for weight-loss surgery should have a preoperative sleep study. Continuous positive airway pressure (CPAP) is the treatment of choice in moderate to severe OSA, and should be instituted prior to surgery in order to reduce the risk of perioperative complications. Bariatric surgery can result in significant improvements in pulmonary function and resolution of some of the respiratory co morbidities such as OSA.

P142 Inflammatory cells in the quadriceps of COPD patients and response to resistance training

Background Physical exercise in healthy individuals leads to an acute inflammatory-cell response in skeletal muscles. In COPD, quadriceps dysfunction is an important systemic manifestation that can be offset by exercise training. However, the nature of the muscle inflammatory response in these patients to acute and chronic exercise remains unknown. We therefore measured inflammatory cell infiltration in the quadriceps of COPD patients and healthy controls, in response to a programme of lower-limb resistance training. Methods 12 COPD patients (mean (SD) age 66.7(7.0) years, BMI 26.1(7.2) kg/m2, FEV1 46.4 (20.5) % predicted, 10 males) and seven healthy controls (66.7 (5.1) years, BMI 27.7(2.4) kg/m2, FEV1 103.4 (17.0) % predicted, five males) underwent 8 weeks of bilateral lower-limb, high-intensity resistance training, thrice weekly, on an isokinetic dynamometer (Cybex II Norm). Quadriceps muscle biopsies from the dominant thigh were obtained at baseline (T0), 24-h after the 1st exercise bout (T1), and 24-h after the last exercise session following 8-weeks training (T2). Glycol methacrylate-embedded muscle biopsies were analysed using immunohistochemistry. Inflammatory cells were identified using antibodies against neutrophil elastase (NE) and CD163 (macrophages). Dual energy x-ray Absorptiometry (DEXA) was used to determine thigh muscle mass and isometric quadriceps strength was measured on the cybex. Results At T0, neutrophils were not detected in any of the healthy controls, but were present in six out of 12 patients. A significant increase in neutrophil and macrophage counts in both patients and controls was seen at T1 (Abstract P142 Table 1). At T2, inflammatory cell counts in both groups were close to baseline values. Isometric quadriceps strength (COPD: pre vs post -134.0 (44.0) vs 151.8 (47.9) Nm, p=0.002; Healthy: pre vs post 153.4 (42.4) vs 169.0 (43.1) Nm, p=0.04] and thigh lean mass (COPD: pre vs post 4.4 (1.2) vs 4.7 (1.2) kg, p=0.003; Healthy: pre vs post 4.5 (0.6) vs 4.7 (0.7) kg, p=0.004] increased significantly after training in both groups. Conclusions Acute resistance exercise in COPD leads to an inflammatory-cell response in the quadriceps that is comparable to healthy controls. Regular training results in muscle adaptation characterised by a diminished inflammatory response to a bout of exercise.Abstract P142 Table 1 T0 T1 T2 NE (cells/mm2 interstitial area) COPD (n=12) 4.1 (0.0–21.0) 137.9 (30.1–217.9)* 0.0 (0.0–15.9)‡ Healthy (n=7) 0.0 (0.0–0.0) 153.4 (13.0–305.5)† 14.2 (0.0–17.3) CD163 (cells/mm2 interstitial area) COPD (n=12) 10.4 (2.1–34.1) 90.3 (40.9–135.7)† 26.9 (12.7–72.5) Healthy (n=7) 0.0 (0.0–27.0) 146.7 (64.3–172.2)† 0.0 (0.0–59.2)§ Values presented as medians (IQR). Data at various time-points compared using nonparametric repeated measures ANOVA (Friedmans Test) and Dunns post test.* p<0.001, T1 vs T0.† p<0.05, T1 vs T0.‡ p<0.001 T2 vs T1.§ p<0.05, T2 vs T1.