Asthma is a condition that affects the airways in your lungs. People with asthma often experience difficulty breathing because these airways become narrow and inflamed. Asthma affects women more severely than men, and we suspect that hormones play a role. We're exploring the potential of using hormone medications, like birth control and hormone therapy (collectively called exogenous sex hormones), to prevent asthma in women and improve outcomes.
To make this a reality, we need to improve our understanding of how hormones impact asthma. Previous studies have given conflicting results, partly because of poorly designed research and treating asthma as a single disease. Asthma is more like a group of related conditions, not just one, similar to having both asthma and high blood pressure or high cholesterol. It's essential to note that not everyone with asthma has high blood pressure or high cholesterol.
Research suggests that conditions linked to high blood pressure or high cholesterol affect asthma, especially in women. To investigate this, we will use a UK-wide database with general practitioner (GP) data to explore if hormone medications, combined with treatments for high blood pressure and high cholesterol levels, can enhance asthma management. The results will help us understand which types of asthma in women are influenced by hormones and pave the way for testing these hormones as potential treatments for asthma.
We aim to improve our understanding of the role of exogenous sex hormones in the development and manifestation of asthma while accounting for phenotypic heterogeneity. We are particularly interested in metabolic syndrome-linked asthma as past research indicates heightened severity in female patients with this phenotype compared to others.
We will construct retrospective open longitudinal cohorts of people aged 16-70 years (follow-up period: January 1, 2005 – December 31, 2019) from Aurum to investigate: the association between exogenous sex hormones and late asthma onset in females with no asthma at the beginning of the follow-up and assess whether this association is dependent on various asthma phenotypes; how exogenous sex hormones affect asthma outcomes (exacerbations, severity, and control) in females with asthma and whether this is affected by asthma phenotypes; whether the association between exogenous sex hormones and asthma is impacted by therapeutic interventions to treat metabolic syndrome. Linked HES data will be used to confirm asthma-related hospitalisations where available.
We will use extended Cox regression for late-onset asthma, either Poisson or negative binomial regression based on the outcome distribution for asthma exacerbations, binary logistic regression for asthma control, and ordered logistic regression for asthma severity. All models will be adjusted for several potential confounding factors. For the identification of asthma phenotypes, we will use both a machine learning-based approach (k-means clustering) and existing recognised phenotypes a priori. To assess how consistent findings are across UK nations, we will repeat the analyses using GOLD. Linked IMD and algorithm-derived ethnicity data will be used to investigate if the associations being investigated differ by socioeconomic status and ethnicity.
The results will offer evidence to pinpoint women who can benefit from sex steroid hormone interventions and those at risk. The findings will contribute valuable insights to asthma guidelines, facilitating targeted management for women with asthma.
New-onset asthma defined as the first General Practitioner (GP)-recorded asthma-specific event (any of the 121 asthma-specific codes that have previously been validated in CPRD and found to have high positive predictive value); Asthma-related outcomes including asthma exacerbations, asthma severity, and asthma control.
Syed Ahmar Shah - Chief Investigator - University of Edinburgh
Syed Ahmar Shah - Corresponding Applicant - University of Edinburgh
Aziz Sheikh - Collaborator - University of Edinburgh
Fatima Almaghrabi - Collaborator - University of Edinburgh
HES Accident and Emergency;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record;CPRD GOLD Ethnicity Record