Development and Application of Methods for Cough Measurement
محفوظ في:
| الحاوية / القاعدة: | PQDT - Global (2025) |
|---|---|
| المؤلف الرئيسي: | |
| منشور في: |
ProQuest Dissertations & Theses
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| الموضوعات: | |
| الوصول للمادة أونلاين: | Citation/Abstract Full Text - PDF |
| الوسوم: |
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| 100 | 1 | |a Holt, Kimberley J. | |
| 245 | 1 | |a Development and Application of Methods for Cough Measurement | |
| 260 | |b ProQuest Dissertations & Theses |c 2025 | ||
| 513 | |a Dissertation/Thesis | ||
| 520 | 3 | |a Chronic coughing, whether refractory or a symptom of respiratory disease, is debilitating and substantially disrupts quality of life, both physically and psychologically. Refractory chronic cough is a condition characterised by hypersensitive airways and hyper-responsive coughing that lasts for more than 8 weeks and persists despite addressing treatable traits. This pathology is thought to be mediated by either central or peripheral neuronal impairment however, precise mechanisms driving chronic coughing are poorly understood and therefore effective targeted treatments are lacking. The slow progression in cough research has partly been attributed to a lack of standardised, validated tools to accurately measure and quantify cough. In addition, no clinically adequate test exists to assist in the identification and diagnosis of patients with cough hyperexcitability. The series of publications and body of work presented in this thesis describe the development and application of two techniques that can be used to objectively and accurately measure cough as a biological signal; cough monitoring and cough challenge testing. Cough monitoring has become the established technique for quantifying cough in clinical studies and evaluating cough therapies and the first half of the thesis presents my original contributions to the development of an approved, validated cough monitoring device and the optimisation of methods to quantify cough frequency. It also explores normal levels of cough frequency in healthy individuals and suggests definitions for new parameters, cough bouts, one of the most disruptive aspects of refractory chronic cough. The second half of the thesis explores capsaicin cough challenge testing, an experimental method designed to evaluate the sensitivity and responsiveness of the neuronal pathways mediating cough. The development of a novel dose-response methodology for capsaicin challenge is presented followed by an application of the capsaicin cough challenge test in a phase II clinical trial to engage a pharmacological target in the airway. XEN-D0501 was shown to successfully block TRPV1 receptors in the lung by significantly reducing capsaicin cough responses yet spontaneous cough frequency and patient reported outcomes did not improve. This observation led to a field-wide shift in thinking around TRPV1 mediated mechanisms underlying refractory chronic cough and highlighted the potential value of the capsaicin cough challenge in clinical studies. Development and acceptance of these tools has advanced knowledge amongst researchers in the field to gain a better understanding of spontaneous cough frequency and the nature of the sensitivity, triggering and responsiveness of the cough reflex in both health and disease. | |
| 653 | |a Physiology | ||
| 653 | |a Software | ||
| 653 | |a Writing | ||
| 653 | |a Signal processing | ||
| 653 | |a Federal regulation | ||
| 653 | |a Research & development--R&D | ||
| 653 | |a Drug dosages | ||
| 653 | |a Sound | ||
| 653 | |a Medical diagnosis | ||
| 653 | |a Patients | ||
| 653 | |a Quality standards | ||
| 653 | |a Data integrity | ||
| 653 | |a Revisions | ||
| 653 | |a FDA approval | ||
| 653 | |a Adenosine triphosphate | ||
| 653 | |a Clinical trials | ||
| 653 | |a Respiratory diseases | ||
| 653 | |a Biomedical engineering | ||
| 773 | 0 | |t PQDT - Global |g (2025) | |
| 786 | 0 | |d ProQuest |t ProQuest Dissertations & Theses Global | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3267204489/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3267204489/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |