The effect of genetic variation on asthma severity and treatment in childhood

1. I have described a population of children and young adults with asthma in primary and secondary care, in terms of relevant history, medication use and exacerbations. 2. My thesis presents observations reported for the first time that asthmatic children and young adults homozygous for the Arg16 allele on the ß2 adrenergic receptor gene (ADRB2), on frequent doses of on demand short-acting ß2-agonists are at greater risk of asthma exacerbations.I have shown an increase in the risk of exacerbations per copy of Arg16 allele in children and young adults with asthma on the regular long-acting ß2-agonist salmeterol. 4. I have shown that there is an increase in risk of exacerbations per copy of Arg16 allele in children and young adults with asthma on frequent (once daily or more) as required doses of inhaled salbutamol. This effect is not observed on participants with asthma who are not exposed to ß2-agonist on a daily basis. 5. I have shown that the Arg16Arg variant status may be associated with worse airway obstruction, as measured by the FEV1/FVC ratio.6. I have shown that the individuals with FLG null alleles have a significantly increased risk of exacerbations requiring hospital admissions, courses of oral steroids, or experiencing school absences