Interpatient variability in rates of asthma progression: can genetics provide an answer?

Asthma is a heterogeneous disorder with a variable natural history. In children 3 patterns of the natural history of asthma have been described: early onset but transient, persistent, and later onset, with only the former leading to persistent asthma later in childhood. In adults a range of different asthma phenotypes differing in their environmental, inflammatory, and prognostic characteristics have also been described. These extend beyond allergic (extrinsic) and nonallergic (intrinsic) asthma to include persistent airflow obstruction and accelerated decrease in lung function over time. Asthma progression can be defined as the change in an individual's phenotype along a continuum ranging from nonasthmatic to asthmatic and subsequent development of severe chronic disease. It is clear that for prevention of asthma progression in patients, there is a need for both better understanding of the pathophysiology of asthma and identification of predictors of progression. Interpatient genetic variability has been shown to affect multiple facets of asthma progression, including increased susceptibility to atopy and subsequent asthma, progression to severe disease, and modification of the response to treatment. Thus genetic testing might provide a means for predicting the likely progression of an individual along the continuum, allowing targeting of preventative treatment. However, the prospect of the use of genetic information in clinical practice raises important social and ethical issues that will need to be addressed before genetic testing can be used to inform the preventative treatment of patients to prevent the development of progression of asthma in individuals.