Allergic etiology and immunology of asthma

Although asthma is a complex and multifactorial disease, a relationship between atopic allergic sensitization to common aeroallergens and asthma has been recognized for decades. This recognition has not led to a widespread immunologic orientation to asthma diagnosis and treatment. This review summarizes older epidemiologic evidence using historical data and skin tests that associate IgE-mediated events with asthma, and presents more recent studies utilizing in vitro testing to study new subject groups, to demonstrate that in certain situations up to 75% to 100% of the cases of chronic asthma, as well as many acute episodes, have an allergic etiology. Thus the old distinctions between intrinsic and extrinsic asthma should be discarded in favor of an aggressive search for allergic factors in virtually any patient with asthma. A theoretic basis for the allergic etiology of asthma has arisen from recent studies linking (1) IgE antibody production with cytophilic sensitization of mast cells and possibly other proinflammatory cell types bearing IgE receptors; (2) IgE-dependent, allergen-induced immediate bronchial reactions with late-phase reactions; and (3) occurrence of late-phase reactions with persistent local inflammation and increased nonspecific bronchial hyperreactivity. Understanding of the allergic etiology of asthma in turn gives rise to renewed emphasis upon immunomodulatory approaches to treatment. At present these include allergen avoidance measures that reduce natural exposure and conventional high-dose allergen injection immunotherapy, both of which have well-documented efficacy when properly applied. In the future, better understanding of the cellular and molecular basis of asthma, in particular the events of the late-phase reaction, are likely to lead to new approaches to treatment based upon rational modulation of these events, possibly with recombinant cytokine-based therapy or synthetic peptide antagonists of defined mediator molecules.