There are marked sex-related differences in the epidemiology of asthma that have been described for several decades. Of particular concern in the context of the proposed study is that asthma is more common in males in the pre-pubertal period, but that this picture reverses in the post-pubertal period. Sex steroid hormones may largely explain these and other sex related differences in asthma epidemiology and outcomes. We have been progressing research in this area, starting with analysis of serial Scottish Health Surveys in which we found substantial reductions in asthma exacerbations among women using hormonal contraceptives. This was followed by a comprehensive systematic review, funded by the Chief ScientistÂ’s Office, which demonstrated that existing studies have major limitations that made it difficult to draw definitive conclusions. To overcome these limitations, we were funded by Asthma UK to further investigate this using the Optimum Patient Care Research Database (OPCRD), a UK-wide GP database. Our analysis found that women using hormonal contraceptives were substantially less likely to develop asthma than women who did not use hormonal contraceptives and that longer duration of use was associated with greater benefit (paper submitted). In this follow-on work, we plan to use CPRD to externally validate our findings from OPCRD. Our ultimate goal is to progress these investigations to the point of evaluating whether hormonal contraceptive use is associated with reduced risk of asthma onset in women of reproductive age. This planned external validation is essential to inform plans for progression to future primary prevention trials.
Female sex steroid hormones have been implicated in sex-related differences in the development of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject. We aim to investigate whether the use of hormonal contraception subtypes and route of administration are associated with asthma onset in reproductive age females. Using CPRD, a national primary care database in the UK, we will construct a retrospective open longitudinal cohort of reproductive age (16–45 years) females. We will estimate the risk of new-onset asthma using Cox regression. We will adjust for confounding factors in all analyses. We will evaluate interactions between the use of hormonal contraceptives and body mass index (BMI) and smoking by calculating the relative excess risk due to interaction and the attributable proportion due to interaction.
New-onset asthma is our key outcome of interest. New-onset asthma will be defined as the first General Practitioner (GP)-recorded asthma event (including diagnosis, hospitalisation, medication prescription or any other asthma event) occurring at least 5 years from the start of the follow-up date. We will exclude individuals with a relevant asthma event recorded up to 5 years after the start of follow-up date. We assume that within a 5-year period, a patient with asthma should have had at least one clinical encounter.
Aziz Sheikh - Chief Investigator - University of Edinburgh
Syed Ahmar Shah - Corresponding Applicant - University of Edinburgh
Bright Nwaru - Collaborator - University of Gothenburg
Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation