Asthma is a common disease affecting the airways of the lungs and is characterised by recurrent episodes of shortness of breath known as exacerbations. Some patients with asthma have high counts of a specific type of blood cell called eosinophils, and several studies have observed that patients with high eosinophils more often experience asthma exacerbations. Very few studies have studied whether patients with high eosinophils may also be more likely to die. Different factors may affect eosinophil levels such as steroid medication and age at which asthma was identified, and these factors may also affect the likelihood of experiencing an asthma exacerbation or dying. This study will look at data collected by general practitioners (GPs) in 4 countries UK, the Netherlands, Denmark and Spain to see whether different blood eosinophil counts result in differences in asthma exacerbations and deaths. This study will also look at whether blood eosinophil levels change over time and what factors may affect eosinophil levels. Asthma patients may benefit in knowing whether routine blood tests that includes eosinophil measurements inform their future risk of exacerbations or dying.
Asthma-related exacerbations remain a significant burden on the healthcare system and can be described as an acute episode of progressively worsening shortness of breath, wheezing, and chest tightness that results in decreased lung function. A severe asthma exacerbation can be defined as: (1) treatment with an initial or increased dose of oral corticosteroids (OCS), (2) an accident and emergency department (A&E) visit, and/or (3) a hospital admission. Eosinophilic asthma, recognisable due to its increased levels of blood eosinophils, has been associated with an increased risk of exacerbations, but few studies have also examined risk of mortality. Factors that may confound associations are inhaled corticosteroid use and age of asthma onset. This retrospective cohort study will identify asthma and severe asthma populations in general practitioners (GP) databases from 4 countries UK, the Netherlands, Denmark and Spain to examine the relationship between eosinophil levels and the risk of asthma exacerbations and death. Incidence rates of asthma exacerbations in strata based on level of blood eosinophils will be estimated. To analyse the effects on risk of severe asthma exacerbations, incidence rate ratios (IRRs) for intermediate and high levels of blood eosinophils compared to low levels will be estimated using crude and adjusted Poisson regression models. To analyse the effects on mortality, Kaplan-Meier curves will be provided showing survival in the three strata based on eosinophil level. Hazard ratios (HRs) for patients with intermediate and high levels of blood eosinophils compared to low levels will be estimated, both crude and adjusted for confounders. This study will also look at the stability of blood eosinophil levels change over time and potential effect modifiers. To describe the stability of the blood eosinophil measurements, generalized linear mixed models will be fitted on log-transformed data to estimate the between and within-patient variance and calculate the intra-class correlation coefficient.
Severe asthma exacerbations and mortality
Melissa Van Dyke - Chief Investigator - GSK
Melissa Van Dyke - Corresponding Applicant - GSK
David Webb - Collaborator - GlaxoSmithKline Research & Development Limited (UK)
Esme Baan - Collaborator - Erasmus University Medical Center ( EMC )
Guy Brusselle - Collaborator - Ghent University Hospital
Katia Verhamme - Collaborator - Erasmus University Medical Center ( EMC )
Maria de Ridder - Collaborator - Erasmus University Rotterdam
Namhee Kwon - Collaborator - GSK
HES Admitted Patient Care;ONS Death Registration Data