Huntington’s disease (HD) is an inherited neurodegenerative condition characterised by progressive motor, cognitive and psychiatric symptoms. The most frequent cause of death is respiratory failure, yet little is known about respiratory function through the progression of the disease or the underlying causes of respiratory failure. A thorough exploration of the relevant literature led to the development of a conceptual framework for respiratory failure in people with HD. Within this framework respiratory failure was characterised as type 1 hypoxaemic and type2 hypercapnic failure and further evaluated through (i) an observational study to investigate respiratory function in people with HD, and (ii) the benefit and feasibility of inspiratory muscle training in people with HD. In order to develop understanding of potential underlying causes of type 1 hypoxaemic and type 2 hypercapnic respiratory failure, the observation study aimed to investigate if there was a difference in respiratory function between healthy controls and people with HD at different stages of the disease, and to explore factors that may influence or be influenced by respiratory function. The framework was further evaluated through the intervention study which investigated the feasibility and benefit of inspiratory muscle training in people with HD as a method of increasing capacity of the respiratory system. Method In the observation study 67 people with HD and 39 healthy control participants underwent a series of measurements of respiratory function based on underlying causes of type 1 hypoxaemic respiratory failure and type 2 hypercapnic respiratory failure. These included measurement of lung volume, respiratory muscle strength and endurance. Exercise capacity, physical activity, swallow and posture as potential influencing factors were also measured in people with HD. In the intervention study 20 people with HD were randomly allocated either to inspiratory muscle training at 50% of maximal inspiratory pressure, or to training against a load suggested to have no effect, completed in the home. The training protocol was 30 breaths, twice daily for six weeks, which was preceded by a habituation period of one week. Sniff nasal inspiratory pressure, peak cough flow and 30 second sit to stand were measured before and after the intervention. The programme was supported by alternate weekly phone calls and home visits. Results All measures of respiratory function, except FEV1/FVC were significantly decreased (p <0.001) in people with manifest HD compared to healthy control participants and people with pre-manifest HD. There was no difference between healthy control participants and people with pre-manifest HD. Respiratory function demonstrated a significant linear decline with disease progression measured by the total functional capacity scale (p<0.001). In particular, peak cough flow was abnormal at the middle stage of the disease. Exercise capacity, physical activity, swallow and posture were significantly related to respiratory function in people with manifest HD (p range 0.016-0.001). In people with manifest HD, exercise capacity was 27.73% ±26.29 predicted and swallow capacity was abnormal in 84.80% of participants. In the intervention study, five participants completed the intervention arm and 7 completed the sham arm. Adherence to the inspiratory muscle training programme ranged from 37-100% across both groups, with mean adherence rates of 70.67% ±26.35 and 74.53% ±21.03 for intervention and sham groups respectively. There was no difference in inspiratory muscle strength, peak cough flow or 30 second sit to stand as a result of the intervention. Participants and their carers identified carer support as a key enabler and life events as a barrier for carrying out the exercises. Conclusion The findings from this study indicate that people with HD are susceptible to type 1 hypoxaemic respiratory failure and predisposed to type 2 hypercapnic respiratory failure due to increased elastic and resistive loads and decreased capacity of respiratory muscles. The risk of type 1 hypoxaemic respiratory failure is high due to decreased swallow capacity and concomitant decreased cough efficacy. Decreased lung volume leading to hypoventilation may be impact on both type 1 hypoxaemic respiratory failure and lead on to type 2 hypercapnic respiratory failure. The predisposition to type 2 hypercapnic respiratory failure is due to decreased respiratory muscle capacity and increased elastic and resistive load. The study also highlighted the complex relationship between respiratory function, exercise capacity and physical activity. Although inspiratory muscle strength, cough efficacy and functional activity remained unchanged in this small sample, the results of the intervention study suggest that inspiratory muscle training is feasible in people with HD. Further studies should use protocols that are directly related to the primary outcome measure e.g. a power based protocol to improve cough efficacy or an endurance based protocol to improve physical activity. A model of respiratory failure in people with HD incorporating both type 1 hypoxaemic and type 2 hypercapnic respiratory failure can be proposed based from the findings of the studies that informs future research and clinical management of people with HD.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:637153 |
| Date | January 2015 |
| Creators | Jones, Una |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/70032/ |
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