The frequent exacerbator phenotype of Chronic Obstructive Pulmonary Disease in pulmonary rehabilitation : assessment of clinical outcomes and inflammation

Chronic obstructive pulmonary disease (COPD) patients who suffer recurrent exacerbations are a recognised clinical phenotype. Pulmonary rehabilitation is considered a cornerstone treatment in the management of COPD. The aim of this thesis was to investigate how frequent exacerbators respond to pulmonary rehabilitation in terms of clinical outcomes and inflammation. Study 1 suggested that frequent exacerbators were less likely to complete pulmonary rehabilitation (44% vs 69%; p=0.025), but those who completed experienced clinically important improvements in outcomes. Study 2 demonstrated that fibrinogen concentrations were significantly reduced in both frequent and infrequent exacerbators (p=0.033), and total leukocyte (p=0.018) and neutrophil (p=0.018) counts reduced in frequent exacerbators only upon completion of pulmonary rehabilitation. Study 3 suggested a tendency towards an increase in MKP-1 anti-inflammatory gene expression in response to corticosteroid treatment (2hr, p=0.060) in both frequent and infrequent exacerbators upon completion of pulmonary rehabilitation. Study 4 showed that an acute bout of exercise at the beginning of pulmonary rehabilitation induced increases in leukocyte counts (p=0.002) and immature neutrophils (p=0.002) in both groups. No differences in inflammatory responses to acute exercise were observed with an acute bout of exercise at the end of pulmonary rehabilitation in both groups. Study 5 suggested that frequent exacerbators recorded fewer daily steps (d=0.3) and spent less time in light (d=0.8) and moderate-to-vigorous activities (d=0.3). There were no definitive differences in inflammation between frequent and infrequent exacerbators. Overall, this thesis shows that pulmonary rehabilitation should be encouraged in frequent exacerbators as they stand to have significant improvements in clinical outcomes and resolution of inflammation.