Squamous cell carcinoma of the lung arises from pre-invasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, their natural history is not well understood and their treatment remains controversial, with radical therapies being offered to individuals who may never develop cancer. Autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that early detection may improve survival. In this thesis, the natural history of pre-invasive disease is described in a prospective longitudinal cohort study. The data identifies a ‘high-risk’ cohort of patients with severe dysplasia and carcinoma in situ, in whom close surveillance detects multiple interval lung cancers at an early stage. The data from this indicates the need of a minimally invasive bronchoscopic treatment for these patients. A further prospective clinical trial evaluates the role of photodynamic therapy in individuals with early invasive carcinomas of the airway who were unfit for conventional lung cancer treatment. Photodynamic laser therapy (PDT) proved to be an effective therapy for patients with small and superficial lesions. However, PDT has not been tested in randomised controlled trials, so a randomised clinical trial (the PEARL trial) was designed to evaluate whether treating high-grade preinvasive lesions will avert progression into invasive carcinoma. Endoscopic laser resection of primary lung carcinoid tumours was also evaluated. This thesis demonstrates that laser can be used to effectively ablate carcinoid tumours. Treatment was particular effective in small intraluminal carcinoid tumours and may be an alternative to surgical resection. Finally, the role of sedation in interventional bronchoscopy was assessed in a prospective study for patients undergoing endobronchial ultrasound and transbronchial needle aspiration. This thesis demonstrates that endoscopist led sedation is comparable to anaesthetic led sedation, but identified the need for a randomised controlled trial
