Cough in lung cancer (LC) is a significant unmet need. There are no evidence-based effective antitussives for its treatment and a lack of well-designed trials incorporating validated cough assessment tools and placebo controls. There is little research on its underlying mechanisms, perhaps with the assumption that it is simply 'due to the cancer'. Therefore, we have sought to characterise cough in terms of its severity, impact on quality of life, frequency and prevalence using LC specific subjective and objective assessment tools for the first time. We have also explored its potential mechanisms and treatment. Published preclinical data show that the substance P/neurokinin-1(NK1) pathway is implicated in cough in 5 different species. This pathway is targeted by the antiemetic aprepitant in humans. Data on the use of aprepitant as a novel antitussive are presented. To characterise cough and assess cough assessment tools in a cohort of patients with LC attending outpatient clinics, subjective and objective cough assessment tools including 24-hour ambulatory cough monitoring (ACM), were used to determine the cough severity, frequency, impact and cough- associated clinical factors in a longitudinal study. To determine cough prevalence, a cross sectional study of all patients attending thoracic oncology outpatient clinics in a single centre over a defined period were approached to determine whether they had a cough, to provide demographic and cancer related data and if applicable, to complete the Manchester Cough in Lung Cancer Scale (MCLCS) cough impact questionnaire and the cough severity visual analogue scale. To explore the role of the NK1 pathway in cough in patients with LC, a single-arm randomised placebo controlled pilot trial assessing aprepitant for the treatment of cough was conducted. The presented data demonstrated that cough affects over half of patients with LC, representing a huge unmet clinical need. Over 2/3rds of patients felt that their cough was severe enough to warrant treatment and over 1/4 described it as painful. Patients with LC suffer from a very severe and frequent cough. Its impact is considerable, with effects on physical, psychological and social domains. The longitudinal study is the first to report that cough severity and impact is predicted by gastro-intestinal co-morbidities rather than cancer related factors. The presented data demonstrate that ACM is feasible and acceptable to patients with LC. This provides researchers with an objective endpoint for use in clinical trials. The MCLCS performs well and is valid. The cough intervention trial is the first to demonstrate that aprepitant is associated with lower subjective cough scores and cough frequency using validated cough assessment tools. No antitussive therapy study has ever shown a positive antitussive effect using both types of cough assessment tools in the LC population. This suggests that the substance P/NK1 pathway is implicated in cough in LC and identifies this as a potential new therapeutic target, providing exciting data and hope for future patients with LC.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:724643 |
| Date | January 2015 |
| Creators | Harle, Amelie |
| Contributors | Smith, Jaclyn |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/the-characterisation-and-treatment-of-cough-in-lung-cancer(f0ba551d-c7c8-4b5c-8d56-9b0c32d6d3ab).html |
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