|dc.description.abstract||Exercise training is an important component of management for people with chronic obstructive pulmonary disease (COPD) and may also be beneficial in people with kyphoscoliosis, with the potential to significantly reduce dyspnoea, increase functional exercise capacity and improve health related quality of life (HRQL). However, individuals with severe disease and limited ventilatory reserve may have difficulty performing exercise training at a sufficient intensity, or for an adequate duration due to severe exertional dyspnoea. Therefore, identification of adjuncts that can reduce dyspnoea and increase ventilatory capacity may be important in order to optimise the benefits associated with exercise training. While short term improvements in dyspnoea and endurance exercise capacity have been observed with a single application of non-invasive ventilation (NIV) during lower limb exercise in people with moderate to severe COPD, it is unclear whether NIV could also be of benefit during functional exercise or during exercise training. In addition, the optimal NIV settings for use during exercise are unknown. The work contained in this thesis aimed to address some of these questions, in particular, the role of NIV as an adjunct during exercise in individuals with chronic hypercapnic respiratory failure (HRF) secondary to very severe COPD or severe kyphoscoliosis.
The literature review presented in Chapter 1 provides a background of the pathophysiology associated with COPD and kyphoscoliosis, and the impact of these conditions on exercise capacity and functional status with a focus on individuals with severe disease and HRF. Common management strategies are described, in particular the use of exercise training and NIV. In addition, the role of NIV as an adjunct during exercise in people with COPD and individuals with kyphoscoliosis is discussed.
The randomised crossover study presented in Chapter 2 aimed to determine the immediate effects of NIV during unsupported arm exercise (UAE) and ground walking on exercise capacity in people with chronic HRF secondary to very severe COPD or severe kyphoscoliosis who were already established on domiciliary NIV. Seventeen participants with chronic HRF performed a series of UAE tests, and 15 participants performed a series of endurance shuttle walk tests, with and without NIV in random order. Non-invasive ventilation during UAE increased endurance time by a mean of 91 seconds (95% confidence interval (CI) 10 to 172, p = 0.031) and reduced dyspnoea by a mean of 2.3 points on the Borg scale (95% CI 1.0 to 3.7, p = 0.002) compared to exercise without NIV. There was a trend for greater walking endurance time with NIV during exercise (119 seconds, 95% CI -17 to 254, p = 0.081), however isotime dyspnoea was unchanged compared to walking without NIV (-1.0 points on the Borg scale, 95% CI -3.0 to 1.0, p=0.29). Non-invasive ventilation during UAE reduced dyspnoea and allowed people with chronic HRF to exercise for longer compared to exercise without NIV in patients with chronic HRF. Investigation of the role of NIV as an adjunct to UAE training is warranted. In contrast, NIV during ground walking did not improve exercise capacity. However, the level of pressure support (PS) provided may have been insufficient as dyspnoea was not reduced.
The level of PS provided during exercise may be particularly important in people with severe kyphoscoliosis as they often have marked chest wall stiffness, and consequently may require high inflationary pressures to support ventilation during exercise. Low level PS of approximately 10 cmH2O during exercise has been shown to improve exercise capacity in people with severe COPD and a limited ventilatory capacity. However, low level PS during exercise decreased distance walked in individuals with severe kyphoscoliosis. In order to determine whether the level of PS delivered during exercise influences the efficacy of NIV during exercise in people with severe kyphoscoliosis and chronic HRF, a double blind randomised crossover study was performed in Chapter 3. Thirteen participants with severe kyphoscoliosis performed four endurance treadmill tests in random order: unassisted; with sham PS; low level PS of 10 cmH2O (PS 10) and high level PS of 20 cmH2O (PS 20). Participants and assessors were blinded to the level of PS delivered during exercise. Endurance time was greater with PS 20 (median 217 seconds, interquartile range (IQR) 168-424) compared with unassisted exercise (median 139 seconds, IQR 111-189), sham PS (median 103 seconds, IQR 88-155) and PS 10 (median 159 seconds, IQR 131-206). In addition, isotime respiratory rate was decreased by 8 breaths/minute (95% CI -11 to -5) and isotime oxygen saturation (SpO2) increased by 4% (95% CI 1 to 7) with PS 20 compared with unassisted exercise. A moderately strong inverse correlation was also found between the change in endurance time and the change in isotime dyspnoea with high level PS relative to unassisted exercise (rS = -0.651, p = 0.016). Therefore, not only was the level of PS provided during walking important in order to increase exercise endurance time, the effect that high level PS had on isotime dyspnoea also influenced exercise performance. The findings of this study indicate that the level of PS delivered during exercise does affect the efficacy of NIV during exercise, and that people with severe kyphoscoliosis require high level PS during walking to improve exercise performance.
While the immediate effects of NIV during exercise appear to be beneficial in people with COPD, reports of NIV during exercise training have yielded conflicting results. In addition, participant numbers are generally small in several randomised controlled trials (RCT) that have assessed the effect of NIV during exercise training in people with COPD, and may have reduced the ability to detect important differences between groups. In order to improve statistical power and determine whether NIV during exercise training can improve exercise capacity, HRQL or physical activity in people with COPD above that of exercise training alone or exercise training with sham NIV, a systematic review and meta-analysis was performed in Chapter 4. Electronic databases (MEDLINE, EMBASE, PUBMED, CENTRAL, PEDro, LILACS, CINAHL, PsycINFO, AMED), conference proceedings, reference lists of included RCTs and relevant review articles were searched up to December 2009 for RCTs of NIV during exercise training in COPD. Two investigators independently selected RCTs and determined the risk of bias of each included study and assessed methodological quality using the PEDro scale. A random effects model was used. Of 7479 reports, 6 RCTs comprising 126 individuals were included in the analysis. The mean ± standard deviation PEDro score was 5.2/10 ± 1.7. Non-invasive ventilation during exercise training increased peak and endurance exercise capacity (mean difference 17%, 95% CI 7 to 27; and mean difference 59%, 95% CI 3 to 114 respectively). No change was found in HRQL although only two RCTs reported this outcome. Physical activity was not measured. Training intensity was higher with NIV (mean difference 17%, 95% CI 3 to 32) and post training isoload lactate was reduced (mean difference -0.96 mmol/L, 95% CI -1.60 to -0.33). This review provides evidence that NIV during exercise training allows people with COPD to exercise at a higher training intensity and to achieve a greater physiological training effect compared with exercise training alone or exercise training with sham NIV. While there was also evidence that training with NIV improved peak and endurance exercise capacity above that of exercise training alone, significant treatment effects were only found when baseline inter-individual differences were taken into account by analysing percentage change data rather than post intervention data. Interpretation of the clinical significance of these results is difficult, as the minimal clinically important difference for the percentage change in peak or endurance exercise capacity is unknown. Further studies are required to assess the impact of NIV during exercise training on HRQL and physical activity.
Exercise rehabilitation may be delayed in people recovering from acute on chronic HRF due to severe exertional dyspnoea. While NIV has been shown to reduce dyspnoea and improve exercise performance in individuals with stable chronic HRF, the effect of NIV during exercise in people recovering from acute on chronic HRF is unknown. To determine the immediate effects of non-invasive ventilation plus oxygen (NIV+O2) during functional exercise compared to exercise with oxygen (O2) alone, a randomised crossover study with repeated measures was performed and is presented in Chapter 5. Eighteen participants performed a series of six minute walk tests (6MWT) and 16 participants performed a series of UAE tests with NIV+O2 and with O2 alone in random order. Total distance walked increased by a mean of 43.4 metres (95% CI 14.1 to 72.8, p = 0.006) with NIV+O2 compared to exercise with O2 alone. Isotime SpO2 also increased by a mean of 5% (95% CI 2 to 7, p = 0.001) and isotime dyspnoea was reduced (median 2 points on the Borg scale (IQR 1 - 4) versus median 4 points (IQR 3 - 5), p = 0.028) with NIV+O2. In addition, a significant inverse correlation was found between the change in total distance walked and the change in isotime dyspnoea with NIV+O2 compared to walking with O2 alone (r = -0.52, p = 0.026). A statistically significant increase in UAE endurance time (median 201 seconds (IQR 93-414) versus 157 seconds (90-342), p = 0.033), and a reduction in isotime perceived exertion (arm muscle fatigue) by a mean of 1.0 points on the Borg scale (95% CI -1.9 to -0.1, p = 0.037) was also observed with NIV+O2 compared with O2 alone. Non-invasive ventilation plus O2 during walking resulted in an immediate improvement in distance walked and oxygen saturation, and a reduction in dyspnoea compared to exercise with O2 alone in people recovering from acute on chronic HRF. The reduction of dyspnoea during walking and arm muscle fatigue during UAE observed with NIV+O2 may allow patients to better tolerate exercise early in the recovery period. The relationship between the reduction in dyspnoea with NIV+O2 and distance walked suggests that selection of ventilator settings that adequately unload the respiratory muscles and reduce dyspnoea is important in order for NIV to be of benefit during ground walking.
A summary of the findings is presented in Chapter 6, along with a discussion of the clinical implications of the findings and suggestions for further research.||en_AU|