Linzy Houchen-Wolloff

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.

Age-specific normal values for the incremental shuttle walk test in a healthy British population.

PURPOSE: The Incremental Shuttle Walk Test (ISWT) is an important functional and prognostic marker in chronic disease. Aging has a detrimental effect on exercise performance. The objective of this study was to produce normal age-specific values for the ISWT in a healthy British population and to explore whether additional variables improve the accuracy of a predictive equation. METHODS: Healthy subjects (N = 152), aged 40 to 90 years, were recruited. Data collection occurred over 2 study visits. Anthropometric and demographic data were collected, and lung function and quadriceps maximal voluntary contraction were measured. An accelerometer was worn for 2 consecutive days at home. The Duke Activity Status Index was completed, and the greatest distance from 2 ISWTs was recorded. RESULTS: One hundred forty subjects (56 men) with mean age (SD) of 59.4 (11.0) years completed 2 ISWTs. Forced expiratory volume in 1 second (FEV1) was 109.1% (14.56%) predicted and ISWT distance was 737 m (183 m). Age-specific normal values for the ISWT were observed: mean (lower limit of normal)—40 to 49 years, 824 m (765 m); 50 to 59 years, 788 m (730 m); 60 to 69 years, 699 m (649 m); and 70 years and older, 633 m (562 m). A predictive equation was developed from 114 subjects. Age, body mass index, FEV1, quadriceps maximal voluntary contraction, and Duke Activity Status Index contributed to ISWT distance predicting 50.4% of the variation in performance. CONCLUSION: We have developed age-specific normal values for performance on the ISWT in a healthy British population. However, even using practical, clinically relevant variables, it is not possible to accurately predict exercise capacity from a regression equation.

The minimum clinically important improvement in the incremental shuttle walk test following cardiac rehabilitation.

Background The aim was to establish the minimum clinically important difference (MCID) in the incremental shuttle walk test (ISWT) following cardiac rehabilitation. Design This was a service evaluation, utilising anchor- and distribution-based methods. Methods Two hundred and twenty patients performed an ISWT following a six-week cardiac rehabilitation programme comprising supervised aerobic exercise, secondary prevention education and a home exercise programme. Primary outcome Patient perception of change in ISWT distance following cardiac rehabilitation. After completing cardiac rehabilitation, subjects were asked to identify, from a five-point Likert scale, their perceived change in exercise performance (range: from ‘better’ to ‘worse’). Two distribution-based methods were also employed (standard deviation (SD) and effect size). The agreement between all measures was observed. Results Mean (SD) age was 65.0 (10.5) years, body mass index 28.4 (5.1), 170 male. The baseline ISWT was 390.8 (173.1) metres (m), which increased to 456.0 (186.7) m (mean change 65.2 (95% confidence interval 55.4–74.9) m after cardiac rehabilitation (p < 0.001)). In those rating their exercise tolerance as ‘slightly better’, the mean improvement was 70.0 (95% confidence interval 51.5–88.5) m. The SD method yielded a minimum clinically important difference value of 36.65 m and the effect size for the change was 0.38. The agreement between the patients’ perception of change and distribution-based methods was poor. Conclusions The minimum clinically important difference for the ISWT following cardiac rehabilitation is 70 m. This patient-reported value is a more sensitive measure and has poor agreement with distribution-based estimates. This value may help clinicians interpret ISWT change in patients, help researchers estimate sample size and aid comparison between studies, when the ISWT is the primary outcome.

Evaluating the Interactive Web-Based Program, Activate Your Heart, for Cardiac Rehabilitation Patients: A Pilot Study

Background Conventional cardiac rehabilitation (CR) programs are traditionally based on time-constrained, structured, group-based programs, usually set in hospitals or leisure centers. Uptake for CR remains poor, despite the ongoing evidence demonstrating its benefits. Additional alternative forms of CR are needed. An Internet-based approach may offer an alternative mode of delivering CR that may improve overall uptake. Activate Your Heart (AYH) is a Web-based CR program that has been designed to support individuals with coronary heart disease (CHD). Objective The aim of this pilot study was to observe the outcome for participants following the AYH program. Methods We conducted a prospective observational trial, recruiting low-risk patients with CHD. Measures of exercise, exercise capacity, using the Incremental Shuttle Walk Test (ISWT), dietary habits, and psychosocial well-being were conducted by a CR specialist at baseline and at 8 weeks following the Web-based intervention. Results We recruited 41 participants; 33 completed the program. We documented significant improvements in the ISWT distance (mean change 49.69 meters, SD 68.8, P<.001), and Quality of Life (QOL) (mean change 0.28, SD 0.4, P<.001). Dietary habits improved with an increased proportion of patients consuming at least 5 portions of fruit and vegetables per day, (22 [71%] to 29 [94%] P=.01) and an increased proportion of patients consuming at least 2 portions of oily fish per week (14 [45%] to 21 [68%], P=.01). We did not detect changes in anxiety and depression scores or exercise behavior. Conclusions We observed important improvements in exercise capacity, QOL, and dietary habits in a group of participants following a Web-based CR program. The program may offer an alternative approach to CR. A mobile version has been developed and we need to conduct further trials to establish its value compared to supervised CR.

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.

Survival following pulmonary rehabilitation in patients with COPD: the effect of program completion and change in incremental shuttle walking test distance

Rationale Pulmonary rehabilitation (PR) in patients with COPD has consistently been shown to produce benefits in exercise capacity, symptoms, and health status. The data surrounding survival following PR are less clear. Our aims were to compare the long-term survival in two cohorts of patients referred for PR; those who successfully completed PR, and a comparator group constructed from patients who either did not complete PR or did not start the program. Additionally, we compared survival between those people who were able to achieve a clinically meaningful improvement in exercise capacity (incremental shuttle walking test) following PR with those who were not. Methods A retrospective longitudinal analysis of clinical service outcomes was conducted to compare the long-term survival in “completers” and “non-completers” of rehabilitation at two hospitals within the University Hospitals of Leicester NHS Trust from January 1, 2000 to February 23, 2012. For “completers”, we also analyzed survival in those meeting (and not meeting) the desired level of change in the incremental shuttle walking test (≥50 m vs <50 m). Results We present to you the largest dataset on this topic (n=1,515). Survival data were ascertained for 823 (54.3%) patients with COPD who had completed a course of PR and for 692 (45.7%) patients who dropped out. Survival time was significantly greater in “completers” compared to “non-completers” of PR (p<0.001). In addition, PR success (≥50 m change in walking distance) was also associated with improved survival (p<0.05). Conclusion The data show an association between completion of PR and survival. In addition, PR success (>50 m change in walking distance) was also associated with improved survival.

Web-based cardiac REhabilitatioN alternative for those declining or dropping out of conventional rehabilitation: results of the WREN feasibility randomised controlled trial

Introduction Cardiac rehabilitation (CR) is typically delivered in hospital-based classes and is recommended to help people reduce their risk of further cardiac events. However, many eligible people are not completing the programme. This study aimed to assess the feasibility of delivering a web-based CR intervention for those who decline/drop out from usual CR. Intervention A web-based CR programme for 6 months, facilitated with remote support. Methods Two-centre, randomised controlled feasibility trial. Patients were randomly allocated to web-based CR/usual care for 6 months. Data were collected to inform the design of a larger study: recruitment rates, quality of life (MacNew), exercise capacity (incremental shuttle walk test) and mood (Hospital Anxiety and Depression Scale). Feasibility of health utility collection was also evaluated. Results 60 patients were randomised (90% male, mean age 62±9 years, 26% of those eligible). 82% completed all three assessment visits. 78% of the web group completed the programme. Quality of life improved in the web group by a clinically meaningful amount (0.5±1.1 units vs 0.2±0.7 units: control). Exercise capacity improved in both groups but mood did not change in either group. It was feasible to collect health utility data. Conclusions It was feasible to recruit and retention to the end of the study was good. The web group reported important improvements in quality of life. This intervention has the opportunity to increase access to CR for patients who would otherwise not attend. Promising outcomes and recruitment suggest feasibility for a full-scale trial. Trial registration number 10726798.

P139 Investigating the profile of physical activity in COPD patients 7 days post discharge from a respiratory-related admission. Does brief advice have an effect?

Introduction and objectives There is a relationship between Physical Activity (PA) and both readmissions and mortality.1 PA in COPD in the immediate period following hospital admission and discharge has not received much attention. This study aimed to investigate the profile of PA in the 7 days following discharge from a respiratory-related admission. Additionally, we explored whether brief PA advice (given as part of a self-management (SM) manual) would improve the rate of recovery, compared to usual care. Methods The study was a Randomised Controlled Trial. Those randomised to UC were discharged with standard treatment and follow-upon addition, those allocated to the SM group received brief advice PA advice in the form of a SM manual (SPACE FOR COPD). All patients wore the ‘Sensewear’ armband (SWA) monitor for 7 days post-discharge for 12 waking hours/day. Outcomes collected were: Total Energy Expenditure (TEE), Steps, Physical Activity Level (PAL) and time spent in light, moderate and vigorous activity. Results Activity data was collected on 25 patients with COPD, UC = 10, SM = 15. Mean (SD) Age-67.7(7.2) years, FEV-1.01(0.43) L, MRC grade-3.8(1. X), 14 Females, 11 Males. Figure 1 shows the serial measures of steps over 7 days. There were no significant differences in physical activity at baseline between the groups. There was little fluctuation in steps over 7 days and the change was not significant from Day 1–Day 7, within in each group. Furthermore, there was no significant difference between the groups. This was the same for all of the other activity monitor data.Abstract P139 Figure 1 Conclusion We found there was no improvement in steps in the 7 days post-discharge, despite PA advice given in the SM group. It may be that the advice was too brief or that 7 days was not long enough to witness an effect. Further research is required to investigate the effects of an exacerbation and SM interventions on PA; capturing PA data prior to, during and after an admission would be of value. Reference 1 Puhan MA, Scharplatz M, Troosters T, Steurer J. Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality – a systematic review. Respir Res. 2005;6:54