Mechanisms of Bronchial Reactivity: The Role of Immunoglobulin E

Abstract

Introduction The fact that asthma can be exacerbated by exposure to dust has been recognized for hundreds of years. In 1921,Kern reported that majority of patients with asthma showed immediate, i.e., wheal and flare, skin tests to extract of dust from their own houses (I). This observation was confirmed, and subsequently Storm van Leeuwenand coworkers (2)demonstrated that if patients weremoved out of their houses into a climate chamber their asthma improved. Thus, by time Rackemann (3)proposed a classification of asthma in 1949 it was widely recognized that a large proportion of patients had extrinsic asthma. At that time, however, major constituents of house dust had not been defined. Immunoglobulin E (lgE) had not been discovered,and only concept of what dust exposure did to lungs was to trigger attacks. Between 1964 and 1970, the world turned upside down. In 1964, Voorhorst and Spieksrna (4) demonstrated that dust mites werethe major source of house dust allergens. In 1967, Ishizaka and coworkers (5) proved that wheal and flare responses weremediated by IgE antibodies. In 1970, Altounyan (6) reported that patients with seasonal asthma had increases in nonspecific bronchial hyperresponsiveness (BHR) during pollen season, which returned to normal in months after season. Dr. Altounyan also showed that a pharmaceutical agent, cromolyn sodium, could reduce this allergen-induced increase in bronchial reactivity (6). Together these three discoveries established basis for many of studies on asthma of last 20 yr. Once it was appreciated that allergens would produce reversible increases in BHR it became obvious to ask whether this was an inflammatory process (7). When Cockcroft and coworkers (8) and others (9, 10) demonstrated that increased BHR after allergen provocation correlated with late bronchial reactions, it was assumed that effect of allergens on BHR must involveinflammation in some waycomparable to known cellular infiltrate of a late reaction in skin. Because in most parts of world most common epidemiologic association with chronic asthma is immediate hypersensitivity to dust mites, central questions became: How do dust mites contribute to nonspecific bronchial reactivity, and why is this apparently restricted to patients who have IgE antibodies?