MEB Seminar: Professor John Henderson
Title: Towards precision and personalized medicine: can epidemiology do better?
Speaker: John Henderson
Professor John Henderson is a professor in Paediatric Respiratory Medicine at University of Bristol. His background is in clinical paediatrics and he has trained in paediatric respiratory medicine, neonatal medicine and paediatric intensive care. Professor Henderson’s early research career was based around physiology of the respiratory system in children and infants. For the past decade, his main research interests have been centred on the epidemiology of asthma and allergy in children, working with the Avon Longitudinal Study of Parents & Children (ALSPAC). He also has a major clinical role in the assessment and treatment of children with neuromuscular diseases and has recently developed a research programme in the evaluation of respiratory muscle function in this group of young people.
Asthma is a complex, polygenic disease, which is highly heritable but with a large increase in prevalence during the 20th Century that was assumed to be driven by environmental exposures interacting with genetic predisposition. Despite massive research efforts, the key environmental drivers of the asthma epidemic remain elusive and most early life influences on asthma risk have only modest effects. One of the possible reasons for this observation is that asthma is highly heterogeneous and may represent more than one pathophysiological entity, which manifest as different phenotypes.
The challenge is to use observable characteristics (phenotypes) to elicit information about the endotypes underpinning these and the environmental influences that are involved in the pathways to disease. Novel approaches to phenotype definition have yielded information that suggests these are truly different but yet they show no obvious differential associations with putative environmental variables, although they do appear to have different genetic associations.
Although birth cohorts have been helpful in understanding the variability of the natural history of asthma and have focused attention on early life as a critical window of exposure, like all observational studies, they carry an inherent risk of bias and confounding. This makes it difficult to infer causal associations and the literature has several examples where experimental (trial) evidence either does not confirm or may show opposite direction of associations reported in observational studies. A number of approaches have been developed to attempt to strengthen causal inference of the myriad of potential exposures that might be associated with both asthma inception and/or severity. The application of these methods to observational studies may increase the efficiency of identifying true causal candidates, which can then be followed up in trials.
Marrying phenotype discovery with improved epidemiological models of causality may contribute to the goal of linking preventative and treatment strategies to specific characteristics of patients and their diseases.Contact person: Catarina Almqvist Malmros