Search

Chronic obstructive pulmonary disease (COPD) is a progressive and disabling condition characterised with an obstruction to expiration that is not wholly reversible. Exercise training is an important component in the management of people with COPD, and improves exercise capacity, health-related quality of life. Bilevel non-invasive ventilation (NIV) during exercise in people with severe COPD is an adjunct that has been shown to increase exercise endurance which may be beneficial in aiding the achievement of an adequate volume of exercise to elicit a physiological training response, which, in turn, can reduce exercise-related breathlessness and allow greater levels of exercise performance. To investigate the effect of bilevel NIV on ventilatory and metabolic variables, and exercise outcomes, measurements with cardiopulmonary exercise test (CPET) systems are required. Exercise testing with CPET systems at atmospheric pressure is common however such measurements could be impacted by the positive pressure when used with bilevel NIV. Determining the accuracy of a commercially available CPET system is important to be able to reliably conduct a trial investigating changes in exercise outcomes with and without bilevel NIV. In people with COPD, airway resistance is increased, and expiratory time during exercise can be insufficient to exhale all the air before chemoreceptor stimulus triggers inspiration. Incomplete lung emptying during exercise increases end-expiratory lung volume above the equilibrium point of the respiratory system and is called dynamic hyperinflation (DH). Once DH raises peak inspiratory volumes to a critical threshold near total lung capacity, the cost of breathing at this high lung volume increases dyspnoea exponentially and limits exercise performance. Bilevel NIV could reduce DH during exercise by changing the pattern of breathing, favouring larger tidal volumes (VT), lower respiratory rates (RR) and a prolongation of expiratory time. The reductions in muscular effort when using bilevel NIV during exercise can also reduce the work of breathing and ventilatory stimulus further reducing DH for the same amount of exercise. Finally, bilevel NIV has an expiratory positive airway pressure (EPAP) which can further offset work of breathing and increase inspiratory capacity at rest. The level of EPAP provided may need to be individualised to account for variations in lung mechanics. Previous studies have reported an increase in time required to aid patients using NIV during exercise and suggest it may not be feasible outside centres without experienced staff to manage both the ventilator and patients using bilevel NIV. Further, even with improvements in exercise capacity, current guidelines recommend that NIV is used in selected individuals who are unable to derive satisfactory gains from standard exercise training. Perceptions of people using bilevel NIV during exercise for the first time are important to inform future research and development of bilevel NIV during exercise. The effect of bilevel NIV on DH and whether a reduction in DH is linked to improved exercise capacity has yet to be investigated. Whether any improvement in exercise capacity or change in DH with bilevel NIV is correlated with resting hyperinflation is also still unclear. In addition, whether an individually titrated EPAP is superior to a standard level of EPAP in reducing DH during exercise and improving exercise endurance time has also not been investigated. Finally, research and evidence on people with COPDs perceptions of using bilevel NIV during exercise is needed. The aims of the work presented in this thesis were to: 1. Examine the effect of measurements with bilevel NIV compared to without bilevel NIV on the measurement accuracy of tidal volume, respiratory rate, oxygen uptake and carbon dioxide production using mechanical simulation of ventilatory and metabolic variables. 2. Determine the effect of bilevel NIV during exercise on DH at isotime exercise and exercise endurance time compared to without NIV. Secondary aims were to determine whether bilevel NIV with an individually titrated EPAP (T-EPAP) was superior to bilevel NIV with a standardised EPAP (S-EPAP) of 5cmH2O, and to describe the physiological effects of bilevel NIV during exercise. Other secondary aims were to determine the effects of participant characteristics, such as resting lung hyperinflation and degree of DH during exercise, on the response to bilevel NIV during exercise (isotime IC and endurance time). 3. Explore the perceptions of using bilevel NIV during exercise in patients with severe COPD who were naive to NIV and evaluate the relationships between individual perceptions of bilevel NIV during exercise and both baseline characteristics and exercise outcomes with bilevel NIV during exercise. The study also aimed to identify potential barriers and facilitators to using bilevel NIV during exercise. This study in Chapter 2 validated the use of a portable CPET system (K4b2, Cosmed, Italy) to measure metabolic and ventilatory variables when bilevel NIV was used during exercise. Benchtop simulation of exercise with the CPET system with and without bilevel NIV showed that ventilatory variables for volume and respiratory rate were not different with compared to without bilevel NIV however accurate measurement of oxygen uptake (V̇O2) during exercise tests was only possible after compensation for pressure with bilevel NIV. Accurate measures of V̇O2 aid the interpretation of results as a reduction in isotime V̇O2 could suggest a reduced work of breathing in people with COPD. This system was used in the randomised crossover clinical trial in Chapter 3. The randomised crossover trial in Chapter 3 of bilevel NIV using either standardised expiratory positive airway pressure (EPAP) of 5cmH2O or titrated EPAP compared to no NIV used the CPET system and compensation equation established in Chapter 2 for measurement of V̇O2 to report the metabolic and ventilatory variables during exercise. The study reported that bilevel NIV reduced DH at isotime and increased exercise endurance time in people with severe to very-severe COPD. Compared to no NIV, there was a statistically significant greater isotime IC with a standardized EPAP (S-EPAP) (MD [95% Confidence Interval (CI)] = 0.19 L [0.10-0.28]), and the change with titrated EPAP (T-EPAP) (0.22 L [0.13-0.32]) exceeded the minimum clinically important difference (MCID) of 200mL for change in IC during endurance cycle exercise. The increase in endurance time during a cycle endurance test with bilevel NIV and S-EPAP (153 s [24- 280]) or T-EPAP (145 s [28-259]), compared to exercise without bilevel NIV was above the MCID of 105 seconds established in exercise training programs. At isotime, in addition to reduced DH, dyspnoea, RR, transcutaneous carbon dioxide (TcCO2) and V̇O2 were also reduced while oxygen saturation (SpO2) and muscle oxygen saturation (SmO2) were increased which may be suggestive of an unloading of the work of breathing. Bilevel NIV may be a useful adjunct to reduce DH and improve exercise tolerance in patients with severe to very-severe COPD. While a method of setting an individualised (titrated) EPAP (4.0 ± 1.2 cmH2O) was successful at increasing IC in the initial titration test, the T-EPAP was very similar to the S-EPAP of 5cmH2O and was not more effective at decreasing DH during exercise or increasing exercise duration. In clinical practice, an EPAP of 5cmH2O appears to be a suitable expiratory pressure to increase exercise time and reduce DH during exercise. Correlations between participants’ baseline characteristics and exercise test outcomes revealed that those with greater resting hyperinflation (residual volume/total lung capacity (RV/TLC)% predicted) had a greater improvement in exercise duration with bilevel NIV compared to those with lower RV/TLC% predicted (r = 0.47) and those with a greater change in IC (or more dynamic hyperinflation) during an incremental peak cycle test had a greater reduction in isotime DH with bilevel NIV during the endurance exercise test (r=0.43). The research supports the use of bilevel NIV during exercise in people with severe to very-severe COPD with resting and/or dynamic hyperinflation, regardless of prior NIV experience, and suggests that bilevel NIV during exercise could be beneficial for more people than just those already using nocturnal NIV. Therefore, it may be useful to measure static lung volumes when considering and selecting people most likely to respond to using bilevel NIV during exercise. In the study in Chapter 4, questionnaires and interviews were used to document participants’ responses during the clinical trial reported in Chapter 3. Participants were naïve to NIV, and all participants revealed generally positive perceptions of bilevel NIV during exercise. Those participants who had an improved exercise endurance time or improved isotime IC from the study in Chapter 3, responded that they could feel the benefit and felt more comfortable using bilevel NIV during exercise than those who benefitted less. Comparing and correlating the physiological responses to the perceptions of NIV during exercise revealed a moderate correlation suggesting people with more resting hyperinflation (ρ = 0.603, p = 0.02) or who hyperinflated more during an incremental exercise test (ρ = 0.488, p = 0.03) were more likely to feel more comfortable with NIV during exercise. During the interviews participants mentioned asynchrony with the ventilator as an issue which has also been evident in previous trials in people with COPD and commented on the full-face mask as a source of possible discomfort as it impeded actions such as swallowing, coughing, and talking. While there was no order effect in the primary quantitative outcomes from the tests in Chapter 3, just over half of the participants (10/19) selected the second test with NIV as their preferred test citing an increase in familiarity and comfort with the device and interface. However, participants highlighted challenges that need to be overcome before they would consider NIV a useful tool at home or during independent exercise training sessions, such as the size and portability of the device and the complexity of managing and using the ventilator, circuit, and interface for independent activity. A summary of the main findings of the studies within this thesis is presented in Chapter 5. Clinical implications, limitations and suggestions for future research are also discussed in this chapter. Overall, the studies in this thesis showed that it is possible to reliably measure ventilatory variables of VT and RR as well as the metabolic variables of V̇CO2 and V̇O2 using a formula that accounted for the effects of pressure on gas density when using a commercially available CPET system (K4b2, Cosmed, Italy) with bilevel NIV compared to measurements without bilevel NIV. In patients with severe to very severe COPD with resting hyperinflation and DH during exercise, bilevel NIV when compared to exercise without NIV, reduced DH, increased exercise endurance time, and reduced exertional dyspnoea. The level of DH during an incremental maximum test and RV/TLC% predicted correlated with improvements in IC and endurance time with bilevel NIV compared to without suggesting bilevel NIV with an EPAP of around 5 cmH2O may be a beneficial adjunct to exercise training in patients with severe COPD who have clinically significant resting hyperinflation and/or DH during exercise. People with severe to very-severe COPD generally had positive perceptions of the use of bilevel NIV during exercise for the first time and regarded bilevel NIV as being an effective tool to reduce breathlessness during exercise and increase exercise endurance. Participants who perceived a greater improvement with bilevel NIV during exercise were more likely to have an actual increase in exercise duration with bilevel NIV during exercise compared to exercise without bilevel NIV and those with higher RV/TLC% predicted were more likely to feel comfortable with bilevel NIV during exercise than those with lower RV/TLC% predicted. The research in this thesis supports the use of bilevel NIV to assist exercise in people with severe to very-severe COPD and hyperinflation.