| Summary: | Introduction. Cystic fibrosis (CF) is the most common fatal genetic disease in the Western world. Fifty years ago, most sufferers died before their first birthday. With improved medical care, survival has now increased to adulthood. Respiratory failure, due to recurrent pulmonary exacerbations, is the main cause of mortality and morbidity. To enable clinical trials of new therapies, biomarkers of pulmonary disease are required. Traditionally, spirometry is used, but this is no longer sensitive enough. The development of chronic hyperglycaemia in CF is associated with accelerated pulmonary decline. Thus this thesis aims to determine if increased airway glucose concentration, 'breath glucose', can be used as a biomarker of pulmonary disease in CF. Methods. Exhaled breath condensate (EBC) was collected and analysed for glucose in 254 adult patients with CF when clinically stable. Breath glucose was estimated from condensate glucose (quantified using high performance liquid chromatography) corrected with a dilution factor (estimated using EBC cation concentration). Intra- and inter-day repeatability for breath glucose was determined. The relationship between breath glucose and clinical variables was established, including: lung function; infection; time to next exacerbation; exacerbation rate. Results. Breath glucose is statistically repeatable, but results are variable and inaccurate for clinical use. The coefficient of variation was 81 ± 38% for within day and 109 ± 39% for between days. Breath glucose was not related to any clinical parameter, including spirometry (p=O.867), sputum microbiology (p=O.251), diabetic status (p=O.706). Breath glucose did not predict time to (p=0.487) or rate of (p=0.463) pulmonary exacerbation within 52 weeks. Conclusion. Breath glucose is not a useful biomarker. Analysis of EBC is technically challenging, so ASL glucose is difficult to quantify accurately. Other studies do suggest an association between hyperglycaemia, airway glucose and pulmonary inflammation. Therefore, this negative result is likely due to methodology.
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