Copyright #ERS Journals Ltd 2001 Eur Respir J 2001; 17: 773±790 European Respiratory Journal Printed in UK ± all rights reserved ISSN 0903-1936 SERIES "CONTRIBUTIONS FROM THE EUROPEAN RESPIRATORY MONOGRAPHS" Edited by M. Decramer and A. Rossi Number 1 in thisSeries Allergy markers in respiratory epidemiology S. Baldacci*, E. Omenaas#, M.P. Oryszczyn} Allergy markers in respiratory epidemiology. S. Baldacci. #ERS Journals Ltd 2001. *Institute of Clinical Physiology, Pisa, ABSTRACT: Assessing allergy by measurement of serum immunoglobulin Ig) E Italy. #Dept of Thoracic Medicine, University of Bergen, Bergen, Norw- antibodies is fast and safe to perform. Serum antibodies can preferably be assessed in } patients with dermatitis and in those who regularly use antihistamines and other ay. INSERM U472, Villejuif, France. pharmacological agents that reduce skin sensitivity. Correspondence: S. Baldacci, Istituto di Skin tests represent the easiest tool to obtain quick and reliable information for the Fisiologia Clinica, CNR, Via Trieste diagnosis of respiratory allergic diseases. It is the technique more widely used, speci®c 41, 56126 Pisa, Italy. and reasonably sensitive for most applications as a marker of atopy. Fax: 39 50503596 Measurement of serum IgE antibodies and skin-prick testing may give complimentary information and can be applied in clinical and epidemiological settings. Keywords: Atopy, eosinophilia, epide- Peripheral blood eosinophilia is less used, but is important in clinical practice to miology, general population, immuno- demonstrate the allergic aetiology of disease, to monitor its clinical course and to globulin E, skin test reactivity address the choice of therapy. In epidemiology, hypereosinophilia seems to re¯ect an Received: December 11 2000 in¯ammatory reaction in the airways, which may be linked to obstructive air¯ow Accepted after revision December 15 limitation. 2000 Eur Respir J 2001; 17: 773±790. The term "allergy" was introduced in 1906 by the immunological and physical-chemical characterization Viennese paediatrician von Pirquet to point out a allowed the identi®cation of the IgND with the IgE. In condition of altered reactivity in a host organism. He 1968 in Losanna, an International Committee of ex- observed that the introduction of an external substance perts of the World Health Organization International in a tissue could alter the tissue reactivity upon a Reference Centre for Immunoglobulins decided to call subsequent contact with the same substance. Previo- this immunoglobulin de®nitively "IgE" recognizing it as usly, the term "allergy" was used to de®ne these altered the 5th antibody class. responses, either protective or harmful. More recently, The discovery of IgE has led to an understanding of this term has been used to indicate an abnormal mo- the mechanisms of allergy. It has also led to the dality ;hypersensitivity) of the organism to respond to development of diagnostic tools as well as analyses and antigenic stimuli ;antigens) which are inactive in normal standardization of allergen extracts. It is possible to subjects [1]. measure not only the pure protein content, but also In 1921, the experiments of two German physicians, the allergenicity in terms of the antigen that reacts with C. Prausnitz and H. KuÈstner, demonstrated that allergy the IgE antibodies. The next possibility is to develop was correlated with a serum factor which was sub- allergens for diagnostic and therapeutic endpoints in- sequently de®ned "reagine" [2]. In 1923 A.F. Coca and cluding immunotherapy [5]. Advanced treatment prin- R. Cooke introduced the term "atopy" to de®ne a con- ciples of immunological modi®cation of the functions stitutional status of predisposition to develop allergic of IgE antibodies and the mechanisms that regulate the diseases as pollinosis and bronchial asthma with a IgE production may in the future include blocking or "reaginic" pathogenesis [3]. The term atopy, of Greek down regulation of IgE in patients with allergic rhinitis etymology, indicates clinical conditions with unusual and asthma [5]. characteristics. Atopy, with or without clinical symptoms, is an For many years, fewinvestigators tried to identify important risk factor for asthma [6], hay fever and and to separate the reagines. Only in 1966±1967, in eczema and creates interest for assessment in epide- Denver, USA, two researches were able to separate, miological studies. Clinicians tend to validate IgE in the serum of atopic subjects, a factor with high antibody testing against its prediction of clinical atopic reaginic activity, pointing out that it did not identify disease, while epidemiologists want to identify indivi- itself with any immunoglobulin ;Ig) class known at duals with atopy regardless of the presence of disease. the time. This newIg wascalled "IgE" [4]. Thus criteria for test positivity in clinical and epide- At the same time, in Sweden, two other researchers, miological settings may differ. H. Bennich and S.G.O. Johansson, identi®ed a newIg In epidemiological surveys, application of biological in a patient with a myeloma, which was de®ned IgND. markers is ideally required to assess the exposure- Furthermore, they observed that high levels of IgND disease relationship [7]. However, allergic sensitization, were present in the serum of atopic subjects [4]. The assessed as serum speci®c IgE antibodies, is not an ERJ baldacci.3d) 30/5/01 09:44:48 Rev 6.03d/W Sep 04 1998) 774 S. BALDACCI ET AL. indicator of allergen exposure alone. In addition to stimulate an immunological speci®c IgE response in allergen exposure, serum speci®c IgE antibodies re¯ect genetically predisposed subjects. The reacting substan- the individual9s susceptibility for allergic sensitization ces, which are immunologically true antigens, are gene- as well as health effects, and may re¯ect more of the rally called allergens [2]. They are heterologous proteins events in the airways when compared to skin tests thus or glycoproteins inducing speci®c allergic reactions in giving additional information [8]. sensitized subjects. Allergens causing atopic reactions Skin tests represent a practicable and reproducible are able to induce IgE production and, by interacting investigation which allows, when correctly performed, with them, to determine clinically evident manifesta- quicker and cheaper results than any other technique in tions. Allergens are classi®ed according to the way of the diagnosis of respiratory allergic diseases. penetration into the organism: by inhalation ;aero- Skin tests give a semiquantitative measure of sensi- allergens), by ingestion, by injection or by contact. tization, as they are supposed to re¯ect the sensitization The aim of this reviewarticle is to summarize the status of airways mucosae. In fact, using a skin test, an epidemiological evidence which has emerged during interaction is arti®cially created between IgE bound to the last decades relating the role of allergic markers mast cells receptors and the same allergens which are such as serum total and speci®c IgE, skin reactivity present in the atmosphere and which are spontaneously and eosinophils in respiratory epidemiology. inhaled. It is important to point out that there has been wide use of skin test reactivity in respiratory epidemiological Total and speci®c immunoglobulin E antibodies studies on general population samples, over recent years, to improve the knowledge on the natural history Clinical and epidemiological importance of airways obstructive diseases. In fact, atopy, as assessed by skin test reactivity, is considered a risk Assessment of IgE antibodies is usually performed factor for asthma and for bronchial hyperresponsive- in order to evaluate atopy. Subjects who are readily ness, which is considered the main functional char- triggered to produce IgE antibodies after exposure acteristic of asthma [9]. However, atopic predisposition, to common environmental allergens are de®ned as as assessed by prick test reactions, seems to be related atopic [14]. This de®nition excludes those who have not only to classical allergic conditions and symptoms, high total IgE levels, but no speci®c IgE antibodies but also to other respiratory problems. against common environmental allergen, as measured In contrast to the "British hypothesis" [10], but in by skin-prick testing or serum speci®c IgE antibodies. agreement with the "Dutch hypothesis" [10], Finnish It also excludes those who have become sensitized only studies showed that atopy predispose to chronic bron- to uncommon allergens [15]. chitis and, furthermore, atopy and smoking seemed to The role IgE plays in immediate-hypersensitivity have an independent and additive effect on both the ;allergic) reactions is well understood. Consequently, prevalence and incidence of chronic bronchitis [10]. nowadays IgE measurements in serum are perform- During the past 20 yrs, there has been a growing ed more frequently as part of routine allergy testing. interest in the effector functions of the eosinophil They are easy to perform, and newmethods and granulocyte, including a variety of clinical conditions equipment make them less expensive to use. Further- associated with hypereosinophilia, such as asthma, more, external quality assurance schemes are routinely allergic diseases, intestinal diseases, joint diseases and used and results of testing are likely to be identical skin diseases [11]. irrespective of where they have been performed. Use Studies of allergy and respiratory disease have tra- of long-acting antihistamines