Inflammatory Profiles in Chronic Obstructive Pulmonary Disease and Asthma

Historically, asthma and chronic obstructive pulmonary disease (COPD) represent polar ends of the spectrum of airways disease defined in part by distinctive profiles of airway inflammation; in practice, overlap can exist between asthma and COPD. This thesis examined the pattern of inflammatory cell infiltration and cytokine expression within the bronchus in COPD and asthma with further study of moderate-severe asthma. In addition using sputum, cytokine expression was further assessed in COPD and asthma and its relation to severity. Based on previous studies, this thesis examined the expression of specifically Interleukin (IL)-13 and Granulocyte Macrophage Colony Stimulating Factor (GMCSF). We demonstrated mast cell myositis in moderate and severe asthma which reflected increased disease symptoms. Preferential localization of inflammatory cells to airway smooth muscle (ASM) was absent in COPD. CD3+ T-cells infiltration of large airway glands was increased in COPD which may influence mucus hyper-secretion. We demonstrated IL-13 overexpression within the submucosa in moderate-severe asthma with specific increase in the ASM in severe disease. IL-13 expression was related to eosinophilic inflammation. In sputum, IL-13 protein was increased in mild and severe asthma reflecting IL-13 expression in ASM. There was a general absence of bronchus and sputum IL-13 in COPD. Sputum GMCSF was increased in moderate-severe asthma and mild-severe COPD. Parallel upregulation of GMCSF and associated receptor (GMCSFr) expression in the submucosa and ASM was present in severe asthma. GMCSF/GMCSFr expression did not exhibit preferential expression in the large airway of COPD. Our findings suggest inflammatory cell infiltration of the airway structures is present in asthma and COPD which may influence the phenotype. In addition IL-13 is important in severe asthma whilst GMCSF is expressed in asthma and COPD across a range of severity, but to a greater degree in severe asthma.