Abstract
Cough is a key symptom of chronic obstructive pulmonary disease (COPD), and leads to impaired health status. During exacerbations, the severity of respiratory symptoms increases and often require treatment in hospital. The mechanisms of cough in COPD is poorly understood. There is evidence to suggest that the activities of the central neural networks for cough may be different between diseases and health. Meanwhile, both stable COPD and COPD exacerbations are associated with inflammation. Bronchopulmonary afferent C fibres can be sensitised by inflammatory mediators, and may lead to heightened cough reflex sensitivity (CRS). This thesis aimed to investigate cough suppression and CRS in stable COPD patients with and without co-existing chronic cough, and compare to patients with chronic refractory cough (CRC) and healthy volunteers. CRS was also investigated during COPD exacerbation, and its relationship with future exacerbation frequency assessed.COPD patients, irrespective of co-existing cough, and healthy volunteers were able to suppress capsaicin-evoked cough whilst patients with CRC were not able to do so. Meanwhile, COPD patients with cough, but not those without, and patients with CRC had heightened CRS compared to healthy subjects. Threshold capsaicin concentrations with and without self-attempted suppression were associated with objective cough frequency in COPD. Cough reflex hypersensitivity (CRH) may therefore play a role in the mechanisms of cough in COPD. Meanwhile, these findings suggest that the reduced efficacy of the inhibitory pathways may be an important mechanism in CRC, and that the mechanism of cough in COPD differs to that in CRC. These observations also collectively support the concept of different phenotypes of cough in respiratory diseases. CRS was heightened during COPD exacerbation and reduced after 6 weeks of recovery. CRS was not associated with objective cough frequency during COPD exacerbation. Therefore, other factors are likely to be driving the frequency of cough during exacerbations. Persistence in CRH following recovery was associated with future COPD exacerbation frequency. The mechanism for this association is unclear, but could be sensitisation of sensory nerves from a persistence of airway inflammation. Meanwhile, CRS and objective cough frequency were repeatable in stable COPD.
Further studies are needed to replicate the findings reported, in particular the association between CRH and prospective exacerbation frequency. The importance of impaired cough suppression neural networks should be investigated in cough associated with other respiratory diseases, and treatments that target this mechanism should be explored. The mechanism of CRH in COPD cough should be investigated, by identifying hypersensitivity to other tussive agents and evaluating the efficacy of antitussive therapies that reduce CRH. The potential of CRS tests to identify patients at high risk of COPD exacerbations should be evaluated, using more simplified methodology.
| Date of Award | 1 Oct 2021 |
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| Original language | English |
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| Supervisor | Caroline Jolley (Supervisor) |