Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that makes it hard to breathe. COPD can lead to long lasting breathing problems and even death. One of the main causes of this disease is smoking cigarettes, but the start of COPD can also be caused by other factors, such as dust. There is no cure for this disease, but symptoms (difficulty breathing) can be managed with treatment. Medicines that are inhaled are used to reduce symptoms, improve health status and exercise capacity. Moreover, inhaled medications for COPD reduce the frequency and severity of exacerbations and thus may decelerate the progression of lung function loss. However, inhaled medications are not effective in all patients and patients may develop side effects despite clinical benefit. We would like to be able to determine the people who will benefit from treatment. Biomarkers that may be useful to determine which patients would benefit such as 'eosinophils' and 'creatine reactive protein (CRP)' can be identified following a simple blood test. People with high levels of these factors in their blood may benefit more from inhaled medicines. This study will aim to see if these biomarkers (eosinophil's and CRP) can help determine which people using inhaled corticosteroid (ICS; a common medication for COPD), will have clinical benefit.
Chronic obstructive pulmonary disease (COPD) is a medical condition characterized by enhanced airway inflammation, and is known to be responsible for mortality and morbidity of millions of individuals worldwide. Recent findings suggest that eosinophils have a key role in the disease pathophysiology. C-reactive protein have also been identified to be elevated in patients with COPD exacerbation. Exacerbations of COPD are the primary outcome as these greatly affect a patient's quality of life. The benefits of inhaled corticosteroids (ICS) to reduce exacerbations have mainly been observed in patients having eosinophil airways inflammation. Similarly, some benefits of ICS have been reported in patients with elevated C-reactive protein levels. Thus, the purpose of this study is to explore the use of ICS and the risk of acute exacerbations, hospitalisations and all-cause mortality among COPD patient with elevated levels of eosinophil (>0.34 x 109 cells/L) and CRP (>3 mg/L). This study will be a cohort study of COPD patients over 40 years from January 2005 to January 2014. Patients with at least one blood eosinophil and CRP measurement at baseline will be included in the study. The primary outcome of the study will be a COPD acute exacerbation (secondary outcomes include: COPD-related hospitalizations or death). We will evaluate the risk of study outcomes stratified by ICS exposure, sex, and age category. Current ICS users will be stratified absolute blood eosinophil count and C-reactive protein using Cox regression analysis (SAS 9.4). We will also adjust for never, past and recent ICS use among current users stratified by eosinophil counts, CRP, gender and age categories for all outcomes. Kaplan-Meier curves will be used to show the differences in survival times with different blood eosinophil counts and CRP level among current users of ICS.
Acute exacerbations of COPD; COPD Hospitalisations; All-cause mortality.
Frank de Vries - Chief Investigator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
Andrea Burden - Collaborator - ETH Zurich
Anke-Hilse Maitland-van der Zee - Collaborator - University of Amsterdam
Anthonius de Boer - Collaborator - Utrecht University
Frits Franssen - Collaborator - CIRO
Johanna Driessen - Collaborator - Utrecht University
Miel (Emiel) Wouters - Collaborator - CIRO
Olorunfemi Oshagbemi - Collaborator - Utrecht University