The term asthma was coined by Hippocrates to refer to the attacks of breathlessness and wheezing experienced by sufferers. Contributors to our understanding of bronchial asthma read like a ‘‘Who’s Who’’of medical history including, among the ancients, Hippocrates and Galen, in the 12th century, Moses Maimonides, and in modern times, European, especially British, physicians (1). For centuries, the attacks of breathlessness characteristic of asthma were thought to be due to abnormalities of bronchial smooth muscle. Over the past two decades, the underlying inflammation associated with asthma, characterized by marked infiltration of eosinophils, has received increasing attention (2). With this recognition has come a renewed appreciation of the value of therapies directed at this inflammation, particularly the effective use of glucocorticoids, and especially inhaled steroids (3). Nonetheless, in spite of new insights into the nature of asthma, it continues to exert a significant toll on patients; evidence shows that it is increasing in prevalence and severity, especially in westernized societies. Indeed, current information suggests that the prevalence of asthma has risen steadily and has doubled over the past 20 years (4). Moreover, asthma continues to be a source of significant mortality in spite of the improved pharmacopoeia available to physicians (5). Asthma is a member of the family of atopic diseases. In 1923, Coca and Cooke (6) proposed the term atopy to refer to the familial occurrence of asthma, allergic rhinitis (hay fever), and dermatitis (atopic dermatitis) associated with positive immediate skin test reactions to environmental antigens, such as ragweed pollen extracts. Prausnitz and Küstner (7) then showed that the sera of allergic patients contain a specific active substance, which in the 1960s was identified by K. Ishizaka and coworkers (8) as the fifth immunoglobulin class, namely IgE. Subsequently, the discovery of an IgE myeloma protein by Johansson and coworkers (9) made reagents for measurement of total IgE protein and IgE antibodies readily available. These new reagents permitted precise characterization of IgE protein levels and revealed that the atopic individual differs from the normal individual by an increased concentration of IgE protein and by a propensity to produce IgE antibodies to a variety of commonly encountered environmental antigens (9, 10). In the 1980s, interleukin (IL)-4 and IL-5 were discovered as critical cytokines regulating the commitment of B cells to IgE and the production of eosinophils by the bone marrow, respectively (11, 12). Immune responses by T lymphocytes were also divided into two classes (13): TH1 responses associated with the production of IL-2 and interferon (IFN)-and TH2 responses associated with the production of IL-4 and IL-5. Analyses of lymphocytes from patients showed that IL-4 and IL-5 expression is associated with atopic disease (14). The increased prevalence of atopic diseases in westernized societies is a subject of great interest especially because it may be due to decreased infectious diseases exposure, especially to tuberculosis, and to a shift of the immune response to the TH2 type (15). Knowledge that bronchial asthma is associated with IgE elevations, especially in younger people, has pointed to an important role for IgE in the pathophysiology of bronchial asthma. Yet, clinicians experienced in the care of patients with asthma recognize that a subset of patients, especially those developing the disease later in life, around the age of 40, experience a form of asthma that is not associated with IgE (and usually not familial), referred to by Rackemann (16) as intrinsic asthma. These patients are …