Developing strategies for the prevention of postoperative pulmonary complications after lung cancer surgery

Lugg, Sebastian Thomas (2023). Developing strategies for the prevention of postoperative pulmonary complications after lung cancer surgery. University of Birmingham. Ph.D.

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Lung cancer is the leading cause of cancer death worldwide with curative intent surgery the most effective treatment. However, there is a risk of developing postoperative pulmonary complications (PPC) including pneumonia and clinically significant lung atelectasis. This thesis investigated the role of cigarette smoking in PPC development, including the impact of smoking cessation and the role of key immune cells in the lung, alveolar macrophage (AMs), with the aim to develop strategies to prevent PPCs in those who smoke before major lung surgery.

In a retrospective study of prospectively gathered data from a cohort of patients undergoing major lung surgery between April 2010 and April 2014, the risk factors and short and long-term outcomes of PPC development were investigated. In those patients with lung cancer diagnosis undergoing major lung surgery, the effect of self-reported smoking status on PPC development and short and long-term outcome after surgery were also investigated. In a translational cohort of patients undergoing lung resection for cancer recruited between August 2018 and August 2021, non-cancerous lung tissue was obtained to isolate AMs and smoking status determined using self-reported status and exhaled carbon monoxide (CO) measurements. AM phenotype was determined and function including efferocytosis, which is a process by which apoptotic neutrophils are removed. A protocol was also developed for a feasibility study of smoking cessation in the lung surgical pathway.

Development of a PPC after lung surgery was found to be associated with worse short-term and long-term outcomes after major thoracic surgery. Cigarette smoking was the biggest risk factor for PPC development, with current smokers having the highest risk of developing a PPC. Self-reported status alone, using a 6-week cut off to determine recent and long-term ex-smokers, the optimum timing for smoking cessation before lung surgery could not be defined. In the translational cohort of patients, the use of exhaled CO found that 1 in 5 patients continued to smoke immediately before surgery. AMs from smokers had increased expression of cell surface markers involved in inhibition of efferocytosis (SIRPα and CD33), and reduced expression of cell surface markers involved in promoting efferocytosis (CD206 and CD163) compared to long-term ex-smokers and never smokers. AMs from patients who were smoking had higher levels of SIRPα, with lower levels found in those who stopped after 4 weeks. Furthermore, AM SIRPα levels were higher and efferocytosis function reduced in those patients who developed PPC.

Smoking is the biggest risk factor for PPC development after major lung surgery, the feasibility of an integrated smoking cessation programme including the web-based application Quit4Surgery needs to be assessed. Modifying SIRPα has a potential role in restoring AM function in those who continue smoking before surgery: the mechanisms of cigarette smoking on SIRPα expression are an area for future research.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Inflammation and Ageing
Funders: None/not applicable
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)

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