Contrary to traditional teaching, patients with Primary Spontaneous Pneumothorax (PSP) do not have normal lungs. Emphysema-like change (ELC) and inflammation are common. However, the natural history of ELC and its significance in terms of future disease is not known. Current management of pneumothorax is generic and not personalised. This thesis updates the UK epidemiology of pneumothorax, describes the use of two novel methods to examine the lungs, a method of predicting early treatment failure, the association of CT findings and recurrence, and a systematic review of chemical pleurodesis to reduce recurrence. Analysis of fifty years' data on ~150,000 admissions demonstrated that the incidence of pneumothorax is increasing, and established a method to identify primary from secondary pneumothoraces and their relative risk of recurrence. Reduced ventilation of hyperpolarised Xenon on enhanced-Magnetic Resonance Imaging (MRI) was seen in those PSP patients with greater low attenuation areas on Computed Tomography (CT) and with reduced pulmonary function. A model of lung inhomogeneity found that metrics of lung ventilation distinguished pneumothorax patients from healthy volunteers and Chronic Obstructive Pulmonary Disease (COPD) patients. This may represent subtle or mild disease, not identified on standard testing, which may be exacerbated by smoking. CT scanning found that mild emphysema and cystic airspaces were common in PSP patients. Ex- or current smokers had more (and larger) cysts. Emphysema was more common in smokers and patients with a history of previous pneumothorax: who were at higher risk of recurrence. However, variation in number and size of cysts were seen in both those patients with and without recurrence. As such, no single algorithm to predict recurrence was identified. Airflow measurement early in the patient pathway has the potential to identify those likely to fail treatment, potentially allowing early triage to surgery. The addition of talc or minocycline as an adjunct to surgery provides the lowest recurrence rates, but physician-led talc poudrage may be similarly effective. Those in whom surgery is not suitable, chemical pleurodesis could be offered via chest drain. Data presented in this thesis thus provides insights into the underlying abnormalities in PSP and lays the groundwork for strategies to fundamentally alter the management paradigm.

Faible masse musculaire a été peu étudiée chez les patients avant le stade terminal de la maladie rénale chronique (MRC). Nous avons évalué la masse musculaire à partir de la créatininurie des 24h pour étudier ses déterminants, son évolution avec le déclin de la fonction rénale ainsi que ses liens avec les risques de progression vers l’insuffisance rénale terminale traitée (IRTT) et de décès avant IRTT. Dans la cohorte NephroTest incluant 1429 patients avec une MRC stades 1 à 4, le débit de filtration glomérulaire a été mesuré par la clairance du 51Cr-EDTA (DFGm) et estimé par l’équation CKD EPI (DFGe). La créatininurie moyenne à l’inclusion diminuait de 15.3±3.1 à 12.1±3.3 mmol/24 chez les hommes et de 9.6±1.9 à 7.6±2.5 chez les femmes, pour une baisse du DFGm de ≥ 60 à < 15 mL/min/1.73 m2. Être plus âgé, avoir un diabète, un faible IMC ou un niveau faible de protéinurie et d’apports protidiques était associé à un niveau faible de créatininurie. Un déclin annuel du DFGm de 5 mL/min/1.73 m2 était lié à une baisse de créatininurie, indépendamment de ces déterminants. Au cours d’un suivi médian de 3.6 ans, 229 patients ont développé une IRTT, et 113 sont décédés avant IRTT. Après ajustement sur les facteurs de confusion, le hasard ratio (HR) était de 1.6 (0.88-2.9) pour le risque de décès et de 0.60 (0.39-0.91) pour le risque d’IRTT, dans le 1er vs 4ème quartile de créatininurie. La baisse de la créatininurie apparait précocement dans la MRC et est liée au décès avant dialyse. La diminution du risque d’IRTT pourrait s’expliquer par un démarrage plus tardif de la dialyse en raison d’une surestimation du DFGm par le DFGe chez les patients avec une faible créatininurie. / Mainly described in patients on dialysis, muscle wasting has received little attention in early stage chronic kidney disease (CKD). We used 24-hour creatininuria to assess determinants of low muscle mass and its putative associations with CKD outcomes, using data from the NephroTest cohort, including 1429 non-dialysis patients with CKD stages 1 to 5. Kidney function was assessed with both measured (mGFR, by 51Cr-EDTA renal clearance) and estimated glomerular filtration rate (eGFR, by CKD-EPI equation). End-stage renal disease (ESRD) and pre-ESRD death were the main studied outcomes. The mean baseline creatininuria decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h in men and from 9.6±1.9 to 7.6±2.5 in women, when mGFR fell from ≥ 60 to < 15 mL/min/1.73 m2. Other determinants of low creatininuria were an older age, diabetes, a lower body mass index, a lower level of proteinuria or protein intake. A fast annual decline in mGFR of 5 mL/min/1.73 m2 was linked with a 2-fold decrease in creatininuria, independent of changes in protein intake and other determinants of muscle mass. Over a median follow-up of 3.6 years, 229 patients developed ESRD and 113 patients died before ESRD. After adjustment for confounders, patients with low muscle mass showed a significantly higher risk for pre-ESRD death (HR 1.6, 95% CI 0.88-2.9), but a lower risk for ESRD (HR 0.60, 95% CI 0.39-0.91). The latter was reversed (HR 1.5, 95% CI 1.01-2.4) when mGFR was replaced by eGFR. Decrease in 24-hour creatininuria may appear early in CKD patients, is related to pre-ESRD death. The lower risk for ESRD may reflect later dialysis start due to overestimation of true GFR by eGFR in patients with low muscle mass.