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 the difficulty in breathing 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 know the people who will benefit from treatment. A blood protein useful identifying these patients is "creatine reactive protein (CRP)" These factors 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 this protein (CRP) can help identify which people that will benefit from corticosteroid (ICS; a common medication for COPD) treatment. We will assess the chances of our study outcomes among patients using ICS or not using statistical software called SAS.
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. 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 patients' quality of life. The benefits of inhaled corticosteroids (ICS) to reduce exacerbations have mainly been observed in patients having elevated CRP levels. More recently, a randomized open-label study among COPD patients found that after 6 weeks of treatment with ICS/long-acting beta-2 agonists CRP levels decreased. Therefore, the aim of this study will be to evaluate the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality with among COPD patients currently exposed to ICS stratified by CRP tertiles compared to ICS naive COPD patients with lowest CRP tertile. This study will be a cohort study of COPD patients aged 40 years or more from January 2005 to January 2014. Patients with CRP measurement at baseline will be included in the study. The primary outcome of the study will be a moderate exacerbation (secondary outcomes include: severe exacerbations or death). We will evaluate the risk of study outcomes stratified by ICS exposure. Current ICS users and ICS naive patients will be stratified by CRP tertiles using Cox regression analysis (SAS 9.4).
Primary outcome:
Moderate-to-severe exacerbations
Secondary outcomes
severe exacerbations and all-cause mortality.
We thank the reviewer for this suggestion. We have now included the following
The primary outcome of interest will be moderate-to-severe exacerbations, which will be defined by validated read codes (H312200, H3y1.00) for an acute exacerbation from the clinical and referral files [1] which has a positive predictive value (PPV) of 96.0% and a sensitivity of 25.1% in identifying acute exacerbations. . The secondary outcome included severe exacerbations, defined as a COPD-related hospitalizations/A&E visit using thread codes (8H2R.00, 66Yi.00) from either the clinical or referral files or the read codes (H312200, H3y1.00) for acute exacerbations from the referral file. We also evaluate the risk of all-cause mortality. Referral files contain referral details recorded by GPs while the clinical file contains all the medical history data entered by the GP [2].
Frank de Vries - Chief Investigator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
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