The relationship between airway obstruction, inflammation and adrenal suppression in children with asthma
File(s)
Author(s)
Selby, Louise Ann
Type
Thesis
Abstract
Asthma describes a constellation of symptoms including wheeze, breathlessness and cough characterised by reversible airway obstruction and airway inflammation. Inhaled corticosteroids (ICS) are the mainstay of treatment. However, in addition to beneficial therapeutic actions, corticosteroids can cause adverse effects, including adrenal suppression.
Adrenal suppression describes the inability to mount an effective cortisol response during stress and infection. Previous studies have found evidence of adrenal suppression in up to 40% of children with asthma however there is no clear dose response. There are potential explanations for this seemingly idiosyncratic relationship. As adherence was not measured there is no way of knowing if prescribed ICS doses were actually taken. Furthermore, adult data suggests there is less systemic absorption of ICS in those with asthma and airway obstruction compared with healthy controls. This thesis investigates the factors that could modulate adrenal function in children with asthma, including airway obstruction, airway and peripheral blood inflammation and adherence to ICS. Screening tests were also carried out to help identify children most likely to have adrenal suppression.
Results of adrenal function testing using a low-dose Synacthen test were available in 42 children. 21 children had adrenal suppression. Children with normal adrenal function demonstrated significantly increased airway and peripheral blood inflammation than those with abnormal adrenal function. There was no relationship between actuated ICS dose and adrenal function.
Adrenal suppression was a common finding in this study; however, measures of airway inflammation, airflow obstruction, dose of ICS and screening tests did not help to identify children at risk of adrenal suppression. Whilst there are clear therapeutic benefits of ICS there must be a balance between effective treatment and preventing adverse effects; the point at which this occurs varies from child to child. Further work is needed to understand why some children are at greater risk than others.
Adrenal suppression describes the inability to mount an effective cortisol response during stress and infection. Previous studies have found evidence of adrenal suppression in up to 40% of children with asthma however there is no clear dose response. There are potential explanations for this seemingly idiosyncratic relationship. As adherence was not measured there is no way of knowing if prescribed ICS doses were actually taken. Furthermore, adult data suggests there is less systemic absorption of ICS in those with asthma and airway obstruction compared with healthy controls. This thesis investigates the factors that could modulate adrenal function in children with asthma, including airway obstruction, airway and peripheral blood inflammation and adherence to ICS. Screening tests were also carried out to help identify children most likely to have adrenal suppression.
Results of adrenal function testing using a low-dose Synacthen test were available in 42 children. 21 children had adrenal suppression. Children with normal adrenal function demonstrated significantly increased airway and peripheral blood inflammation than those with abnormal adrenal function. There was no relationship between actuated ICS dose and adrenal function.
Adrenal suppression was a common finding in this study; however, measures of airway inflammation, airflow obstruction, dose of ICS and screening tests did not help to identify children at risk of adrenal suppression. Whilst there are clear therapeutic benefits of ICS there must be a balance between effective treatment and preventing adverse effects; the point at which this occurs varies from child to child. Further work is needed to understand why some children are at greater risk than others.
Version
Open Access
Date Issued
2023-08-21
Date Awarded
2024-04-01
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
License URL
Advisor
Fleming, Louise
Saglani, Sejal
Bush, Andrew
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)