Modulation of airway inflammation in COPD

COPD is a preventable, treatable, slowly progressive condition, associated with an abnormally amplified inflammatory response, characterised by an accelerated decline in lung function, punctuated by exacerbations. Exacerbations cause considerable mortality, morbidity, and cost. Airway inflammation in COPD is mainly neutrophilic although eosinophilic airway inflammation plays an important role, particularly during exacerbations. Inflammation in foregut derivatives outside the lung may contribute to amplification of airway inflammation. I have shown that a management strategy aiming to minimise eosinophilic airway inflammation as well as symptoms is associated with a significant 62% reduction in the frequency of severe exacerbations of COPD. This strategy was associated with no overall increase in corticosteroid treatment; there was evidence that increased corticosteroid therapy was targeted to patients with eosinophilic airway inflammation and benefit was largely confined to these patients. I have shown an association between the sputum differential neutrophil count and airway bacterial load, and showed that a one week course of Levofloxacin significantly reduced both the % neutrophil count and bacterial load in patients with stable state COPD and bacterial load > 10^6 cfu/ml. I have shown that the prevalence of peptic ulcer disease increases progressively with increasing severity of COPD in miners with homogeneous risk factors for development of COPD, and that peptic ulceration was a strong and independent predictor of a low FEV_1% predicted and FEV_1\bigFVC ratio. In another population I showed that H. Pylori seropositivity was more common in patients with COPD compared to healthy smokers matched for age and occupation. We have shown that TREM-1 can be measured from induced sputum and is potentially a novel marker of bacterial infection and neutrophilic airway inflammation during exacerbations. Further work is required to ensure that measurement and modulation inflammation of airway results in improved clinical outcomes, and is made more clinically viable.