Blood eosinophilia, withdrawal of inhaled corticosteroids and risk of COPD exacerbations and mortality

Date of ISAC Approval: 
Lay Summary: 
Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that is characterised by airway narrowing and loss of lung tissue. COPD can lead to chronic 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 environmental and genetic factors. There is no cure for this disease, but symptoms can be managed. Inhaled corticosteroids (ICS) use are not effective in all patients, meaning some patients continue to have COPD related problems. We would like to be able to identify the people who will benefit from ICS treatment, in order to avoid use where clinical benefits of use are not apparent. "Eosinophils" are believed to help identify patients who will benefit from ICS. Patients with high eosinophil levels in their blood are believed to show worsening of their disease on withdrawal of ICS. These ICS are regularly prescribed in COPD patients in order to prevent exacerbations. The aim of the study is to investigate whether stopping of ICS will lead to increased number of moderate or severe exacerbations and mortality in patients with high blood eosinophils compared to low blood eosinophils.
Technical Summary: 
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow obstruction is a major cause of morbidity and mortality worldwide. Smoking and noxious particles results in irreversible damage to the lungs. Although eosinophilic airway inflammation is usually considered a feature of asthma, it has also been recently found to play an important role in COPD patients. Exacerbations play an important role in the progression of airflow limitation, deterioration of health status and increased mortality of COPD patients. Therefore, preventing exacerbations is one of the major goals in the treatment of the disease. Traditionally, inhaled corticosteroids (ICS) are prescribed to reduce exacerbations. However, ICS are associated with side effects and are ineffective in some patients. Patients with elevated eosinophil's are believe to benefit from ICS. The aim of this study is to evaluate the effects of withdrawal of ICS among COPD patients with varying blood eosinophilic inflammation on the risk of exacerbations, hospitalisation/accident & emergency visits and all-mortality. We will use Cox regression analysis to identify the risk of the acute exacerbation, hospitalisation and all-cause mortality adjusting for relevant confounders, among patients with different blood eosinophil levels. Withdrawal of ICS will be determined time-dependently.
Health Outcomes to be Measured: 
- Acute exacerbations of COPD - COPD Hospitalisation - all-cause mortality

Frank de Vries - Chief Investigator - Utrecht University
Dr Anke-Hilse Maitland-van der Zee - Collaborator - University of Amsterdam
Anthonius de Boer - Collaborator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
Frits Franssen - Collaborator - CIRO
Johanna Annemariek Driessen - Collaborator - Utrecht University
Miel (Emiel) Wouters - Collaborator - CIRO
Olorunfemi Oshagbemi - Collaborator - Utrecht University
Suzanne van Kraaji - Collaborator - Maastricht University Medical Centre