Stratification of respiratory disease through early diagnostic sampling

Ferguson, Jenny (2025) Stratification of respiratory disease through early diagnostic sampling. PhD thesis, University of Glasgow.

Abstract

Both lung cancer and Coronavirus Disease 2019 (COVID-19) present with a wide range of prognoses and eventual outcomes. In both conditions early diagnosis and commencement of treatment (where appropriate) can improve survival. Given the spectrums of disease seen in lung cancer and COVID-19, stratification of patients also aids in the selection of the most appropriate individual management options to further optimise patient outcome. The overall aim of this thesis is to examine the stratification of respiratory disease through early diagnostic sampling.

Chapter 2 describes the design and delivery of the multi-centre, prospective STRATIFY study (Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion). It has been established from retrospective data that those presenting with early stage, otherwise potentially radically treatable non-small cell lung cancer (NSCLC) and minimal pleural effusion do significantly worse in terms of survival than those without such effusions. Based on this previous retrospective data it has been hypothesised that this difference in survival is due to the presence of occult pleural metastases (OPM) not otherwise detected in the routine diagnostic work up of those with suspected NSCLC and minimal pleural effusion. STRATIFY was therefore designed as the first prospective, multicentre, observational study with the primary aim of determining the true prevalence of OPM in this cohort of patients through the addition of thoracoscopy to the diagnostic pathway.

Unfortunately, due to a multitude of issues many of which stemmed from the COVID-19 pandemic, recruitment to STRATIFY was slower than expected and therefore the decision to close the trial to recruitment was taken in May 2024. Primary outcome data including the prevalence of OPM and important safety data for the 27 recruited patients are however included here.

Patients with lung cancer (and many other common malignancies) often present with large pleural effusions which go on to be proven malignant through simple aspiration. The diagnostic yield of pleural fluid cytology is well documented at 60% on average but varies considerably by tumour type. The yield of predictive markers from effusion cytology, which are now mandated in the diagnostic work up of lung and breast adenocarcinoma, is less well established. Chapter 3 of this thesis therefore aimed to assess the utility of pleural fluid cytology for the detection of predictive markers in lung and breast adenocarcinoma in a real-world setting. This multicentre, retrospective cohort study found that the full panel of predictive marker (PM) testing required by contemporaneous international cancer treatment guidelines was returned in only 20% of cases where these were requested on pleural fluid cytology. Performance differed by individual marker with yields for many markers improving over the time period of the study. No clinico-radiological factors were significantly associated with PM testing yield to guide pre-aspiration likelihood of success.

Perhaps even to a greater extent than lung cancer, outcomes from COVID-19 are markedly heterogeneous with some patients complaining of little to no symptoms while others go on to develop potentially fatal pneumonitis. Although risk factors for poor prognosis are well documented, less is understood about the individual immune response and how these immunological events affect disease outcome. In chapter 4 individual immune response at the time of COVID-19 diagnosis and how this relates to disease severity was examined. In keeping with previous work, severe COVID-19 (as defined by the need for supplemental oxygen) was associated with obesity and hypertension (p= 0.0456, p= 0.0071 respectively) in this cohort. Flow cytometry of baseline serum samples revealed lower activation (phosphorylation) of STAT 5 in response to stimulation across almost all immune cell subpopulations in those with severe disease. Interrogation of potential mechanisms linking metabolic syndrome and the altered STAT5 signalling observed are ongoing by collaborators at the time of writing.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by the Chief Scientist Office Scotland.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Funder's Name: Chief Scientist Office Scotland
• Supervisor's Name: Blyth, Professor Kevin and Tsim, Dr. Selina
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85356
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 16 Jul 2025 15:21
• Last Modified: 16 Jul 2025 15:21
• URI: https://theses.gla.ac.uk/id/eprint/85356

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