Most adult asthma has its origins – and causes – in childhood; the sharp rise in the prevalence of childhood disease in most European countries in recent decades indicates important environmental determinants acting on a genetically susceptible population, a process commonly referred to as gene–environment interaction. The nature of the relevant drivers remains unclear, but the distribution of the disease suggests that they are associated with a ‘Western’ environment, possibly reflective of urbanisation and less exposure to microorganisms that are protective against asthma and allergy (the ‘hygiene hypothesis’). Genome-wide association studies have identified a handful of asthma genes that account for only a small fraction of the heritability of asthma, but epigenetic silencing and activation of genes involved in asthma are likely to be other important mechanisms that determine susceptibility to asthma and that underlie gene–environment interactions (see chapter 3).
Immunopathological studies of the airways in asthma have pointed to the presence of a T-helper type 2 (Th2)-associated inflammatory process involving cytokines such as interleukin (IL)-4, IL-5 and IL-13 with a predominant eosinophilic inflammation, associated with features of airway remodelling (airway fibrosis, increased smooth muscle mass and epithelial fragility). Better understanding of the inflammatory processes has paved the way for novel, specifically targeted therapies.