Development of a conceptual model of childhood asthma to inform asthma prevention policies.

BACKGROUND: There is no definitive cure for asthma, as prevention remains a major goal. Decision analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modelling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma. METHODS: We reviewed currently available decision analytic models for asthma prevention. A steering committee of economic modellers, allergists and respirologists was then convened to draft a conceptual model of paediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model. RESULTS: Consensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of 'patient characteristic', 'family history' and 'environmental factors'. To be capable of modelling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modelling phased implementation and gradual and incomplete uptake of the intervention. CONCLUSIONS: Economic evaluation of childhood interventions for preventing asthma will require modelling of several codependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention.

Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization.

BACKGROUND: Allergic disease is the most frequent chronic health issue in children and has been linked to early-life gut microbiome dysbiosis. Many lines of evidence suggest that microbially derived short-chain fatty acids, and particularly butyrate, can promote immune tolerance. OBJECTIVE: We sought to determine whether bacterial butyrate production in the gut during early infancy is protective against the development of atopic disease in children. METHODS: We used shotgun metagenomic analysis to determine whether dysbiosis in butyrate fermentation could be identified in human infants, before their developing allergic disease. RESULTS: We found that the microbiome of infants who went on to develop allergic sensitization later in childhood lacked genes encoding key enzymes for carbohydrate breakdown and butyrate production. CONCLUSIONS: Our findings support the importance of microbial carbohydrate metabolism during early infancy in protecting against the development of allergies.