THE DEVELOPMENT OF SPECIALIZATION IN ALLERGY—A Historical Review and a View Ahead

Clinical allergy as a special field of practice is a little more than twenty-five years old. The organized efforts of the two national societies for the study of allergy and the many county, state and regional groups of physicians interested in allergic diseases have served to bring all workers in the field together in pursuit of a common objective. However, the foundation stones for the specialty were laid by a number of astute clinical observers during the past hundred years.This historical sketch aims to portray these men and their work, and points out how the introduction of the skin test as a diagnostic method has dominated the clinical approach to allergic diseases during the past half-century—and that the technique is gradually losing some of its significance. This changing emphasis from the older diagnostic procedures to other techniques is the results of the discovery of the new hormones, cortisone and corticotropin (ACTH). These hormones have presented another method of studying the mechanism of allergic phenomena in man. Finally, brief reference is made to the growing recognition of the significance of the psychosomatic factors in the management of the allergic patient and the influence of this and the other additions to knowledge on the training of the future generations of allergists.     

The management of allergic patients; the role of the internist

There has been an increasing trend in the United States toward intensive specialization in allergic diseases. Whereas the tendency toward specialization has led to greater knowledge of the scientific aspects of allergic phenomena, it has somewhat diverted the specialists' attention from the many clinical problems that await solution. Effective treatment of the allergic patient depends in no small measure on the broad viewpoint and clinical experience of the internist. This fact has been reemphasized by the growing awareness of the significance of the secondary or precipitating causes, such as climatic, nutritional, hormonal and psychogenic factors which influence allergic manifestations. Overemphasis on specialization in allergic diseases with their wide ramifications may defeat the main objective-a successful therapeutic result. To meet this challenge, the internist should be trained in allergy and yet retain a broad approach to the more basic problems of internal medicine. This objective may be attained by certain modifications in undergraduate medical instruction in allergy. Postgraduate training sponsored by our national allergy societies affords internists an excellent opportunity to advance their knowledge of clinical allergy.     

THE MANAGEMENT OF ALLERGIC PATIENTS—The Role of the Internist

There has been an increasing trend in the United States toward intensive specialization in allergic diseases. Whereas the tendency toward specialization has led to greater knowledge of the scientific aspects of allergic phenomena, it has somewhat diverted the specialists'' attention from the many clinical problems that await solution.Effective treatment of the allergic patient depends in no small measure on the broad viewpoint and clinical experience of the internist. This fact has been reemphasized by the growing awareness of the significance of the secondary or precipitating causes, such as climatic, nutritional, hormonal and psychogenic factors which influence allergic manifestations. Overemphasis on specialization in allergic diseases with their wide ramifications may defeat the main objective—a successful therapeutic result.To meet this challenge, the internist should be trained in allergy and yet retain a broad approach to the more basic problems of internal medicine. This objective may be attained by certain modifications in undergraduate medical instruction in allergy. Postgraduate training sponsored by our national allergy societies affords internists an excellent opportunity to advance their knowledge of clinical allergy.     

Allergy as a systemic disease

The prevalence of allergic diseases has shown an increase in the last few years. Allergic diseases develop in persons with a genetic background, this genetic trait being known as atopy. The main pathophysiological characteristic of allergy is inflammation. The inflammatory process may explain the diversity of symptoms and signs of allergy. The early sensitization increases the risk of developing different symptomatic forms of allergy, and one person may present different symptoms and signs of allergy. But some persons can become allergic without atopy trait in conditions of a higher and longer exposure to allergens (e.g. occupational allergy). In the last years new allergens have induced symptoms, sometimes with a life-threatening evolution. The load of allergen in public areas is also increasing. In this context, allergy must be understood as a unique systemic disease with various forms of presentation.     

Primary structure, recombinant expression, and molecular characterization of Phl p 4, a major allergen of timothy grass (Phleum pratense)

Grass pollen allergy is one of the most important allergic diseases world-wide. Several meadow grasses, like timothy grass and rye grass, contribute to allergic sensitizations, but also allergens from extensively cultivated cereals, especially rye, make a profound contribution. The group 4 allergens are well known as important major allergens of grasses. We have cloned for the first time group 4 sequences from Phleum pratense, Lolium perenne, Secale cereale, Triticum aestivum, and Hordeum vulgare, and investigated the IgE-reactivity of recombinant Phl p 4 as a candidate for allergy diagnostic and therapeutic applications.     

肠道微生物与过敏性疾病关系研究进展

目前,过敏性疾病的防治主要依赖于使用抗生素,然而抗生素的滥用已造成了严重的危害。近年来随着肠道微生物相关研究的不断深入以及人们对过敏性疾病的日益关注与重视,肠道微生物与过敏性疾病间的关系逐渐受到科学家们的关注。调整肠道菌群结构可能为过敏性疾病的防治提供新的思路。目前对肠道微生物与过敏性疾病间的相关性报道相对较少且未有深层次的剖析。本文总结了关于肠道微生物与过敏性疾病关系的研究起源、发展与现状,旨在为过敏性疾病的防治提供新策略。     

The immunomodulatory role of probiotics in allergy therapy

The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.     

Food products and allergy development, prevention and treatment

In westernized countries allergic diseases have reached epidemic proportions. Food is frequently a perpetrator of allergy but, in turn, modified food and selected food ingredients can become valuable intervention tools in the fight against allergy. There are two basic approaches towards mitigation of food allergy through nutrition: to reduce the allergenicity of raw food materials by physical, chemical or genetic methods or to influence host immunity towards a non-allergic state using various food ingredients. Dietary intervention for the prevention and therapy of allergy is an emerging field where initial findings from animal studies are now being validated in human trials. Nevertheless, to consolidate the utility of such interventions, more pre-clinical and clinical studies remain necessary.     

Animal models of allergic bronchopulmonary aspergillosis

Among the allergic fungi, Aspergillus fumigatus, a saprophytic mold, distributed widely in the environment is a frequently recognized etiologic agent in a number of allergic conditions. Among the different allergic diseases caused by this fungus, allergic bronchopulmonary aspergillosis (ABPA) is by far the most significant one. The immunopathogenesis of this disease is not fully understood. Although several immunomodulatory treatments are available for allergic disease, none of them are applicable or relevant or useful in fungal induced allergy. It is essential to understand the pathogenesis of the disease including the antigen induced immunoregulation and the resulting factors, such as cytokine, chemokines, pathways activating factors, inflammatory and airway remodeling factors need to be understood for intervening with appropriate treatment. Animal models are essential in understanding these features of the disease. Several models of allergic aspergillosis have been developed in recent years in various animals. However, murine models have been studied more carefully and extensively. The exposure to antigen in mice leads to allergy very similar to ABPA with high IgE, elevated peripheral blood and lung eosinophils, pulmonary inflammation, and airway hyperreactivity. The role of various cytokines and chemokines and their receptors were also studied. In addition, immunotherapy and vaccination have been attempted in recent years using the murine model of ABPA. This review covers the murine model of Aspergillus induced allergy and asthma and presented critically our current understanding of the subject and the potential application of such a model in future for developing treatment modalities. This revised version was published online in June 2006 with corrections to the Cover Date.     

Serum biomarkers in interstitial lung diseases

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.     

Toxoplasma gondii Infection Induces Suppression in a Mouse Model of Allergic Airway Inflammation

Allergic asthma is an inflammatory disorder characterized by infiltration of the airway wall with inflammatory cells driven mostly by activation of Th2-lymphocytes, eosinophils and mast cells. There is a link between increased allergy and a reduction of some infections in Western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofecal and foodborne microbes such as Toxoplasma gondii. We previously showed that both acute and chronic parasite T. gondii infection substantially blocked development of airway inflammation in adult BALB/c mice. Based on the high levels of IFN-γ along with the reduction of Th2 phenotype, we hypothesized that the protective effect might be related to the strong Th1 immune response elicited against the parasite. However, other mechanisms could also be implicated. The possibility that regulatory T cells inhibit allergic diseases has received growing support from both animal and human studies. Here we investigated the cellular mechanisms involved in T. gondii induced protection against allergy. Our results show for the first time that thoracic lymph node cells from mice sensitized during chronic T. gondii infection have suppressor activity. Suppression was detected both in vitro, on allergen specific T cell proliferation and in vivo, on allergic lung inflammation after adoptive transference from infected/sensitized mice to previously sensitized animals. This ability was found to be contact- independent and correlated with high levels of TGF-β and CD4(+)FoxP3(+) cells.     

Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis,and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis

BackgroundAllergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.ConclusionsWe observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.Please see later in the article for the Editors'' Summary     

Non-Immunologic Factors in Allergic Diseases

Many different explanations of the mechanism of asthma and other allergic diseases have been offered. Of these, the immunologic concept has gained the greatest acceptance. During the past 25 years, a renewed attempt to place the diagnosis and treatment of allergic diseases on a firm scientific basis has yielded many fundamental facts and principles in such varied fields as immunology and psychiatry, but no one of these disciplines affords a satisfactory approach to the practical management of the individual patient. There is a vast gap between scientific fact and medical practice. The need at present is less for basic principles than for their rational application to diagnosis and treatment. This requires a broad knowledge of the basic sciences, and utilization of that which is applicable.     

Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model

Background

Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.

Objective

This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model.

Methods

Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.

Results

In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.

Conclusions

Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.     

Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations.

OBJECTIVE--To investigate clinical features of acute allergic reactions to peanuts and other nuts. DESIGN--Analysis of data from consecutive patients seen by one doctor over one year in an allergy clinic at a regional referral centre. SUBJECTS--62 patients aged 11 months to 53 years seen between October 1993 and September 1994. MAIN OUTCOME MEASURES--Type and severity of allergic reactions, age at onset of symptoms, type of nut causing allergy, results of skin prick tests, and incidence of other allergic diseases and associated allergies. RESULTS--Peanuts were the commonest cause of allergy (47) followed by Brazil nut (18), almond (14), and hazelnut (13). Onset of allergic symptoms occurred by the age of 2 years in 33/60 and by the age of 7 in 55/60. Peanuts accounted for all allergies in children sensitised in the first year of life and for 82% (27/33) of allergies in children sensitised by the third year of life. Multiple allergies appeared progressively with age. The commonest symptom was facial angioedema, and the major feature accounting for life threatening reactions was laryngeal oedema. Hypotension was uncommon. Of 55 patients, 53 were atopic--that is, had positive skin results of tests to common inhaled allergens--and all 53 had other allergic disorders (asthma, rhinitis, eczema) due to several inhaled allergens and other foods. CONCLUSIONS--Sensitisation, mainly to peanuts, is occurring in very young children, and multiple peanut/nut allergies appear progressively. Peanut and nut allergy is becoming common and can cause life threatening reactions. The main danger is laryngeal oedema. Young atopic children should avoid peanuts and nuts to prevent the development of this allergy.     

THE PLACE OF ALLERGY IN MEDICINE

Much of the management of uncomplicated allergic disease has fallen within the province of the general practitioner and the specialist who does not limit his practice to allergy. This is the result of the simplification of standard techniques, the availability of excellent post-graduate instruction and the increasing quality of commercially prepared desensitizing extracts and other material. The newer drugs, particularly the antihistamines and the corticosteroids, have made the symptomatic care of patients with severe diseases of allergic origin less complicated.As a result, the physician who limits his practice to allergy has become more of a specialist, in that he is called upon only to deal with the more difficult cases. Since the practice of allergy involves many parts of the body and often overlaps other recognized specialties, it cannot fall into the classification of any one already recognized medical specialty. It is desirable, therefore, that an American Board of Allergy be established to set up criteria for practice and to examine and qualify applicants.     

Use of an in vitro allergy test for the differential diagnosis of human brucellosis and yersiniosis

The degree of the allergic reorganization in the body of brucellosis and yersiniosis patients was determined by the study of their blood and serum samples in the in vitro allergy test (the direct and indirect leukocytolysis test). The allergy test is highly specific and recommended as a differential diagnostic method in brucellosis and yersiniosis infections.     

Radioimmunologic tests in children with pruritus and with a combination of pruritus and allergic respiratory disease

Radioimmunological tests were carried out in 180 children with pruritus and 167 children with pruritus and allergic respiratory diseases. Difference between these groups was statistically insignificant in case of food allergy. Results of RAST were more often positive in case of respiratory allergy in the patients with pruritus and coexisting allergic respiratory diseases than in patients with skin involvement only. Reaction was more intense and allergy polyvalence measured with RAST was higher. All differences were statistically significant (p less than 0.001 or 0.01). Mean IgE levels was higher in children of all age groups in case of pruritus coexisting with allergic respiratory diseases.     

Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy

Allergic diseases, including asthma and food allergies, are an increasing health concern. Immunotherapy is an effective therapeutic approach for many allergic diseases but requires long dose escalation periods and has a high risk of adverse reactions, particularly in food allergy. New methods to safely induce Ag-specific tolerance could improve the clinical approach to allergic disease. We hypothesized that Ag-specific tolerance induced by the i.v. injection of Ags attached to the surface of syngeneic splenic leukocytes (Ag-coupled splenocytes [Ag-SPs]) with the chemical cross-linking agent ethylene-carbodiimide, which effectively modulate Th1/Th17 diseases, may also safely and efficiently induce tolerance in Th2-mediated mouse models of allergic asthma and food allergy. Mice were tolerized with Ag-SP before or after initiation of OVA/alum-induced allergic airway inflammation or peanut-induced food allergy. The effects on disease pathology and Th2-directed cytokine and Ab responses were studied. Ag-SP tolerance prevented disease development in both models and safely tolerized T cell responses in an Ag-specific manner in presensitized animals. Prophylactically, Ag-SP efficiently decreased local and systemic Th2 responses, eosinophilia, and Ag-specific IgE. Interestingly, Ag-SP induced Th2 tolerance was found to be partially dependent on the function of CD25(+) regulatory T cells in the food allergy model, but was regulatory T cell independent in the model of allergic airway inflammation. We demonstrate that Ag-SP tolerance can be rapidly, safely, and efficiently induced in murine models of allergic disease, highlighting a potential new Ag-specific tolerance immunotherapy for Th2-associated allergic diseases.