Non-invasive markers of airway inflammation in the clinical assessment and management of asthma

Recently there has been interest in assessing airway inflammation using non-invasive tests as it has been shown that controlling eosinophilic airway inflammation, as measured in induced sputum in a population of patients with moderate to severe asthma, can lead to a reduction in asthma exacerbations, when compared to current guidelines.;Most patients have mild to moderate asthma and are treated solely in primary care, in a setting not suitable for induced sputum measurements; there exists a need for an easy, safe and inexpensive mechanism for monitoring airway inflammation.;Previous work has demonstrated that the fraction of nitric oxide in the exhaled breath (FENO) is elevated in asthma and that levels decrease after steroid use. These papers led to an explosion of interest in using FENO as a marker for eosinophilic airway inflammation in asthma. However, few studies have evaluated FENO in a clinical setting and compared its use to management protocols.;This thesis explores the relationship between airway inflammation and asthma, and focuses on induced sputum and FENO. I explore the relationship between sputum eosinophil counts and FENO in an observational study, and use these findings to calculate levels for FENO which best identify the presence and absence of a sputum eosinophilia. These levels are then used in a randomised clinical trial, assessing whether FENO measurements can help predict and prevent asthma exacerbations when compared to current clinical guidelines.;Lastly, a large cross sectional study explores the relationship between pre- and postbronchodilator FEV1 and measures of airway inflammation, allowing for the effect of confounding factors, using a multivariate analysis.