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.

Neuromuscular stimulation of quadriceps in patients hospitalised during an exacerbation of COPD: a comparison of low (35 Hz) and high (50 Hz) frequencies.

BACKGROUND: Neuromuscular electrical stimulation (NMES) has shown to improve skeletal muscle strength and exercise capacity in stable patients with chronic obstructive pulmonary disease (COPD). Variations in NMES protocols are considerable. We aimed to compare changes in muscle strength after high-frequency and low-frequency NMES in patients admitted to hospital with an acute exacerbation of COPD. METHODS: Patients were referred for inpatient (IP) rehabilitation during hospitalisation for an acute worsening of their COPD. They received 30-minute daily NMES to both quadriceps at a frequency of 35 or 50 Hz. NMES intensity was titrated to patients' tolerance. Isometric quadriceps muscle strength and endurance walking (ESWT) time were measured at baseline and on hospital discharge. RESULTS: A total of 10 patients in each treatment group underwent NMES during hospitalisation (mean [SD] age 68.0 [±7.4] years, FEV1 0.99 L [±0.58], FEV1/FVC 47% [± 27%], MRC 5 [IQR ±1]). There were no significant differences in baseline characteristics between groups. Muscle strength (legs combined) increased in both groups regardless of the NMES frequency used (35 Hz--3.8 ± 4.9; 50 Hz--3.4 ± 5.5 kg). This was only significant within the 35 Hz group. The change in ESWT also showed a trend to increase in both groups (35 Hz--109 ± 92.7; 50 Hz--145.6 ± 94.7). There was no significant difference between groups for either outcome. CONCLUSION: NMES is a feasible intervention to improve muscle strength in a cohort of patients admitted with an exacerbation of COPD. The response appears to be independent of the frequency used and both were well-tolerated.

Pulmonary rehabilitation: WHAT WE KNOW AND WHAT WE NEED TO KNOW.

The multidisciplinary treatment of pulmonary rehabilitation (PR), which includes exercise training, self-management education, and psychosocial and nutritional intervention, is now a standard of care for chronic obstructive pulmonary disease (COPD) and has been incorporated into major guidelines. We must now focus efforts on improving its impact and widening its applicability. What is the direction of PR; where does it fit in the comprehensive care of the COPD patient; and how can clinicians best apply this important intervention? This was the charge of the roundtable discussion, Pulmonary Rehabilitation: Moving Forward, involving 20 experts from North America and Europe, which was convened in Fort Lauderdale, Florida, in early 2008. It is not meant to be an exhaustive review; rather, this report summarizes the roundtable proceedings, while providing direction to best position PR into the continuum of COPD care. By consensus, it was agreed upon that although PR is effective for other chronic respiratory diseases, the discussion focus was COPD since most of the evidence base and patient referral are for this disease. These proceedings provide insight into 3 broad areas appropriate for investigation or implementation: positioning PR in an integrated care model for COPD patients; improving the effectiveness of this intervention; and expanding the recognition, application, and accessibility to PR. It is the hope that this document will provide a catalyst for clinicians, investigators, and healthcare policy makers to help realize these goals as well as serve to suggest important areas for future research and development in PR.

Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease.

RATIONALE: Skeletal muscle strength and bulk are reduced in patients with chronic obstructive pulmonary disease (COPD) and influence quality of life, survival, and utilization of health care resources. Exercise training during pulmonary rehabilitation (PR) can reverse some of these effects. In athletes and healthy elderly individuals, dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training, thereby increasing muscle mass. OBJECTIVES: This article examines the effect of CrS on functional exercise capacity and muscle performance in people with COPD. METHODS: One hundred subjects with COPD (mean [SD] age, 68.2 [8.2] yr; FEV(1), 44.0 [19.6] %predicted) were randomized to a double-blind, placebo-controlled, parallel group trial of CrS during 7 weeks of PR encompassing aerobic and resistance exercises. Subjects ingested creatine (22 g/d loading for 5 d; maintenance, 3.76 g/d throughout PR) or placebo. Baseline, postloading, and postrehabilitation measurements included pulmonary function, body composition, peripheral muscle strength, and functional performance (shuttle walking tests). A volunteer subgroup (n = 44) had pre- and postloading quadriceps muscle biopsies. MEASUREMENTS AND MAIN RESULTS: Eighty subjects completed the trial (38 creatine, 42 placebo). All outcome measures significantly improved after PR. There were no significant differences between groups post-PR (mean [SD] change in incremental shuttle walk distance, 84 [79] m in the creatine group vs. 83.8 [60] m in the placebo group; P = 1.0; knee extensor work, 19.2 [16] Nm [Newton meters] in the creatine group vs. 19.5 [17] Nm in the placebo group; P = 0.9). Muscle biopsies showed evidence of creatine uptake. CONCLUSIONS: This adequately powered, randomized, placebo-controlled trial shows that CrS does not augment the substantial training effect of multidisciplinary PR for patients with COPD. Clinical trial registered with https://portal.nihr.ac.uk/Pages/NRRArchiveSearch.aspx (NO123138126).

The effect of auditory feedback on phonation threshold pressure measurement.

The effect of auditory feedback on phonation threshold pressure (Pth) measurement was investigated in 14 females with normal, untrained voices. Two measurement systems (Glottal Enterprises MS 100--circumferentially vented mask and Kay Elemetrics Aerophone II--non-circumferentially vented mask) were examined under three conditions: (1) masked, (2) no mask, and (3) masked with enhanced auditory feedback-acoustic signal placed at ears through headphones. Masked with enhanced auditory feedback, in addition to subject training, significantly lowered Pth values regardless of mask design. The amount of auditory feedback provided by different mask designs was investigated and revealed a significant difference. Clinical significance of different auditory feedback levels provided by the two mask designs was investigated. Direct comparison of the mean values between systems was not possible because of each system's design and calibration. Comparisons were accomplished by subtracting means of select-paired conditions (masked/no mask; masked/masked plus masked with enhanced auditory feedback) within each system and then comparing these difference scores from the same paired conditions between each system. No clinical significance in difference scores was revealed because of varying amounts of auditory feedback provided by the masks. Results support the use of enhanced auditory feedback, in addition to subject training, when measuring Pth.