Tackling asthma phenotypes in community studies

Episodic wheezing with variable airflow obstruction (asthma) defines a syndrome that is well recognised and much studied. It is now clear that this syndrome is heterogeneous in its clinical features, treatment response, prognosis and pathophysiological mechanisms. Causation remains elusive, yet the differences in asthma prevalence across the world,1 the effect of migration on changing asthma prevalence2 and the rise in asthma prevalence in the past decades highlight very potent gene and environmental effects that modify the clinical expression of asthma.3

Studying asthma heterogeneity is a useful way to disentangle these complex issues.4 The intense focus on allergic mechanisms has given us very precise understanding of the Th2–eosinophil mechanistic pathway, effective and specific treatment—for example, anti-immunoglobulin E (IgE) monoclonal antibody treatment—and shown that a primary prevention strategy based on this approach is not likely to be beneficial.

Current attention is focusing on patterns of granulocyte infiltration, specifically the presence or absence of eosinophils and neutrophils.5 There is clear heterogeneity in these responses among adults with asthma, where a non-eosinophilic pattern of response is associated with more severe persistent asthma, non-response to corticosteroid therapy and certain specific trigger factors such as tobacco smoking and occupational exposures. Furthermore, it is also possible to link the granulocyte response patterns to key immunological mechanisms, such as eosinophils with Th2 lymphocyte responses and neutrophils with dysfunctional innate immune responses.6 This approach integrates basic mechanisms with clinical asthma heterogeneity to yield endogenous asthma phenotypes, or “endotypes”.7

While the application of the …