Determinants of exacerbation frequency in COPD.
Doctoral thesis, UCL (University College London).
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease is interspersed with exacerbations; periods of acute symptomatic, physiological and functional deterioration. There are large differences in yearly exacerbation incidence rates between patients of similar COPD severity giving rise to the concept of two distinct phenotypes; frequent and infrequent exacerbators. This thesis hypothesizes that frequent exacerbators are a distinct phenotype of COPD, and identifies some of the factors that influence exacerbation frequency. Method: 356 individuals from the London COPD cohort were included in the analyses in different subgroups. All patients completed daily diary cards and reported exacerbations to the study team for sampling and treatment. Blood and sputum were collected in the stable state and at exacerbation. Samples were processed for cytokines, genetic polymorphisms and viruses. A subset of patients also had endobronchial biopsies for epithelial cell work and immunohistochemistry. Results: Patient reported exacerbation frequency can be used to accurately stratify patients into frequent and infrequent exacerbators groups in subsequent years. Frequent exacerbators were more depressed and more likely to be female then infrequent exacerbators. There was no difference in social contacts, HRV positivity or load in sputum, Vitamin D levels, or cytokine variability between frequent and infrequent exacerbators. No differences in genetic polymorphisms (ICAM-1, IL-6, IL-8, VDR, Taq1 α1 –antitrypsin) were identified between the two groups. Conclusions: The frequent exacerbator phenotype exists. There is not one single determinant of exacerbation frequency, and determinants vary with underlying disease severity.
|Title:||Determinants of exacerbation frequency in COPD|
|Open access status:||An open access version is available from UCL Discovery|
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