Al-Malky, GMA; (2014) An analysis of ototoxicity in children: Audiological detection, clinical practice and genetic susceptibility. Doctoral thesis , UCL (University College London).

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Abstract

Ototoxicity is the damage to the ear from exposure to medications. The inner ear is the commonest site of damage where cochlear and/or vestibular functions are affected. Ototoxic medications can cause irreversible toxicity, with aminoglycosides (AGs) and cisplatin being the most established agents. A series of studies are reported in this research under three main themes. Theme A focused on audiological assessments and assessment tools; Theme B focused on causation; and Theme C focused on the impact of ototoxicity and current service provision. The main Theme A study was a clinical observational study with a cross-sectional design assessing the auditory status of children with cystic fibrosis (CF) exposed to AGs. Theme B investigated potential risk factors and aspects in genetics that may be associated with increasing patient susceptibility to the ototoxic effect of AGs. Theme C assessed the effect of ototoxicity on the quality of life (QoL) of children surviving cancer. It also included a survey of current UK practice regarding auditory monitoring for ototoxicity. The novel outcomes of these studies included showing that the prevalence of AG ototoxicity in children with CF is higher than previously reported and evaluating the efficacy of auditory assessment tools. They stressed the importance of choosing appropriate criteria to define ototoxicity and identified potential risk factors associated with it. The genetic studies highlighted a rare case of normal hearing in a child with the m.1555 A>G mutation despite exposure to AGs. They complemented the limited research on the impact of ototoxicity in children on their QoL and on current practice. The latter identified gaps in the provision of ototoxicity monitoring services in the UK, especially due to the absence of nationally agreed guidelines. This research has generated recommendations for several future studies and has informed the clinical management of patients with CF.

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