Scientific Information

 

What is the incidence of allergies in Australia?

According to the Australasian Society of Clinical Immunology the frequency of allergic disease has approximately doubled in the past few decades in Australia and New Zealand and around:
• 1 in 3 people will develop allergies at some time during life • Food allergy occurs in around 1 in 20 children and in about 1 in 100 adults • 1 in 5 will develop atopic dermatitis • 1 in 6 will have an attack of hives (urticaria) • 1 in 10 people have asthma • 80 per cent of children diagnosed with allergic rhinitis (hayfever) will still have trouble 10 years later • 85 per cent of children with atopic dermatitis (eczema) improve by their teenage years, but often have dry and irritable skin and problems with soap and some cosmetics for life • 40 per cent of young adults will still be sneezing 20 years later • Allergic rhinitis affects 1 in 5 Australians • 1 in 100 will have a life-threatening allergy known as anaphylaxis.

Notable Studies:

Potential non–immunoglobulin E–mediated food allergies: Comparison of open challenge and double-blind placebo-controlled food challenge

Otolaryngology–Head and Neck Surgery (2007) 137, 803-809

De Yun Wang, MD, PhD, Bruce R. Gordon MD, Yiong Huak Chan, PhD and Kian Hian Yeoh, MD, Singapore, and Hyannis, MA

Objective:

Comparison of open food challenge (OFC) with double-blind placebo-controlled food challenge (DBPCFC). Undertaken by a prospective sequential randomized challenges.

Results:

All Patient reacted to at least 1 food and to all challenges with the same food, with multiorgan symptoms in the nose, nervous system, throat, and lung. There was a correlation in the type and severity of symptoms (P 0.015) for OFC and DBPCFC, and both were significantly (P 0.01) more sever than placebo. Compared with DBPCFC, OFC sensitivity was 66%, and positive predictive value was 89%.

Conclusion:

This is the first study showing both concordance of OFC and DBPCFC and also that intradermal tests can identify reactive foods that can be verified by DBPCFC. Because most tests for IgE-mediated food allergy were negative, observed reactions were probably non–IgE mediated. Read more

Safety and efficacy of radioallergosorbent test-based allergen immunotherapy in treatment of perennial allergic rhinitis and asthma

Otolaryngol Head Neck Surg. 2004 Nov;131(5):673-8.
Source: National University of Singapore, Department of Otolaryngology, Singapore.
ABSTRACT:
Objective: This study was undertaken to demonstrate the safety and efficacy of in vitro, radioallergosorbent test (RAST)-based inhalant allergen immunotherapy. Study Design: Prospective 22 year single site clinical study, with outcome evaluations of 480 perennial allergic rhinitis patients, including 96 with concomitant asthma. Results: Rhinitis symptom control after 2 years of immunotherapy was excellent in 32.5% of patients, good in 45.6%, and fair in 14.2%. There was no improvement in 7.7%. For patients with asthma, 81% had good or excellent pulmonary symptom improvement, and no patient failed to improve. No severe reactions occurred, but there were 5 limited systemic reactions, or 0.008% of injections, during a 2.5-year mean immunotherapy treatment course. Conclusion: RAST-based immunotherapy is safe and effective for patients with perennial allergic rhinitis, with or without concomitant asthma. Significance This is the first large, multiyear study of safety and efficacy of RAST-based immunotherapy for treatment of perennial allergic rhinitis and asthma. EBM rating: C. Read more

Antigen induced asthma attenuated by neutralization therapy

Boris M, et al. Clin Ecol. 1985;3:59-62. ABSTRACT: The effect of neutralization therapy on animal antigen-induced asthma was tested. The neutralization dose was determined by the serial dilution technique. Subjects received, in a double blind crossover study, either the neutralizing dose or placebo followed by animal antigen bronchoprovocation challenge.
Evaluation through pulmonary function tests demonstrated significant protection after neutralization therapy

Provocation/neutralization

King WP, et al. A two-part study. Part I. The intracutaneous provocative food test: a multi-center comparison study. Otolaryngol Head Neck Surg. 1988;99:263-71. ABSTRACT: This study investigated the clinical usefulness of the intracutaneous provocative-neutralization food test (IPFT). Thirty-seven patients were tested for five identical food allergies by eight physicians in different geographical locations. Throughout the study, comparison was made between the IPFT when interpreted by skin response (IPFT SK) and when interpreted by symptom provocation (IPFT PR). Double-blind IPFT results were compared with those of previously accomplished oral challenge food tests (OCFT). IPFT reliability was determined by a double-blind comparison of the initial IPFT, with two subsequent IPFTs performed 7 days apart. Correlation of the IPFT SK and IPFT PR with the OCFT provided validity coefficients of 0.78 and 0.61 respectively, both significant beyond the 0.01 level of confidence. Reliability of the IPFT SK and IPFT PR was shown to be 0.68 and 0.40, respectively. The IPFT SK was significant beyond the 0.01 level of confidence and the IPFT PR was significant beyond the 0.05 level of confidence. King WP, et al. Provocation/neutralization: A two-part study. Part II. Subcutaneous neutralization therapy: a multi-center study. Otolaryngol Head Neck Surg. 1988;99:272-7. ABSTRACT: Presented is a triple-blind crossover study that investigates the efficacy of subcutaneous neutralization food hypersensitivity therapy. Seven physicians and thirty-three patients from various parts of the country participated. Each patient underwent three 2-week treatment sessions, with 1 week off treatment between each session. During each treatment session, one injection a day was given. The injection consisted of a placebo for one 2-week session, and the active allergen during the other two sessions. The active dose was determined by earlier intracutaneous provocative food testing. The diet during the study period was not varied. Medication-symptoms diaries were maintained and treatment result evaluations for both individual complaints and overall results were detailed on a standard form at the end of each treatment session. While the number of foods treated per patient varied from 1 to 13, the majority were treated with 3 to 5 foods.
Treatment with the active medication was more efficacious than with placebo.
A few patients’ symptoms were aggravated with the active medication. This indicates a correct diagnosis, but incorrect treatment dose. In the clinical setting such adverse response should be reversed.
Overall, neutralization subcutaneous treatment should be beneficial approximately 75% of the time, and further enhanced by supplemental diet manipulation.

Immunological mechanisms of allergen-specific immunotherapy

Larché M, Akdis CA, Valenta R.
Nat Rev Immunol. 2006 Oct;6(10):761-71. Allergen-specific immunotherapy (SIT) involves repeated administration of the sensitizing allergen (usually by subcutaneous injection or, more recently, by sublingual application).  SIT was first reported at the beginning of the last century and has been shown to be a robust and clinically effective allergen-specific form of treatment that induces active immunity to the allergen.  SIT is disease modifying, rather than palliative, and has a duration of action that exceeds the treatment period.  It has been shown to prevent the onset of new sensitizations to different allergens and to reduce the development of asthma in patients with allergic rhinitis caused by inhaled allergens. SIT improves the quality of life of the treated individuals, through the reduction of symptoms and medication usage.  More specifically, it has been shown to reduce seasonal increases in specific IgE and in the nonspecific airway hyper-reactivity that occurs in individuals with asthma.  Bronchial responses to an inhaled allergen challenge, and late-phase responses to an allergen challenge in the skin or nasal mucosae, are also reduced. Read more

Food allergy in migraine

Monro JA. Proc Nutr Soc. 1983;42:241-6. SUMMARY:
This study corroborates the long-held view that migraine is due to food allergy. The immunological mechanisms have yet to be defined but treatment by immunotherapy has been effective in controlling symptoms in the double-blind study.

Elimination of oral food challenge reaction by injection of food extracts

Rea WJ, et al. Arch Otolaryngol. 1984;110:248-52. ABSTRACT: Twenty subjects underwent a double-blind evaluation by analyzing six variables to determine if subcutaneous injection of the food extract neutralizing dose would protect subjects from reactions. Twelve subjects had four of the six variables neutralized 60% of the time following the food antigen neutralizing dose. The placebo trials neutralized four of six variables 15% of the time.
The sign/symptom results show statistical significance favoring food extract neutralization over placebo.
The remaining eight subjects had at least two of the six variables neutralized by the food extract up to 85% of the time. It appears that the phenomenon of subcutaneous food neutralization can be scientifically endorsed for clinical use in the treatment of food reactions.

Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite

Clin Allergy. 1986 Sep;16(5):483-91.
Abstract:
In a double-blind placebo-controlled cross-over trial, low dose sublingual therapy with house dust mite was effective in relieving symptoms in 72% of the group of patients with perennial rhinitis due to house dust mite (P less than 0.03). Following active treatment, there was a significant increase in morning peak nasal inspiratory flow rate (P less than 0.01) in those who improved (thirteen out of eighteen) and resistance to nasal provocation with house dust mite also increased, in some cases up to 1000-fold (P less than 0.05). Oral therapy is safe and avoids the side effects of desensitizing injections which can be serious. The potential for oral desensitization is great and further studies on this form of treatment are needed. Read more

 

Scientific Research:

 

Neural Pathways in Allergic Inflammation

L.Mirotti, 1 J. Castro,1 F. A. Costa-Pinto,2 andM. Russo Department of Immunology, Institute of Biomedical Sciences & School of Veterinary Medicine & Animal Science, University of Sáo Paulo, Brazil Journal of Allergy Vol 2010, Article ID 491928, 11pages doi:10.1155/2010/491928  ABSTRACT: Allergy is on the rise worldwide. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The association between allergy and altered behavior patterns has long been recognized. The molecular and cellular pathways in the bidirectional interactions of nervous and immune systems are now starting to be elucidated. In this paper, we outline the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the neural modulation of allergic responses. Read more

Neural correlates of IgE-mediated food allergy

Alexandre Salgado Basso, Frederico Azevedo Costa Pinto, Momtchilo Russo, Luiz Roberto Giorgetti Britto, Luiz Carlos de Sá-Rocha.
Journal of Neuroimmunology Volume 140, Issue 1, Pages 69-77 (July 2003)
ABSTRACT: Although many authors have considered the possibility of a direct interaction between food allergy and behavioral changes, the evidence supporting this hypothesis is elusive. Here, we show that after oral ovalbumin (OVA) challenge, allergic mice present higher levels of anxiety, increased Fos expression in emotionality-related brain areas, and aversion to OVA-containing solution. Moreover, treatment with anti-IgE antibody or induction of oral tolerance abrogate both food aversion and the expression of c-fos in the central nervous system (CNS).
Our findings establish a direct relationship between brain function and food allergy, thus creating a solid ground for understanding the etiology of psychological disorders in allergic patients. Read more

Without nerves, immunology remains incomplete-in vivo veritas

Shepherd AJ, Downing JE, Miyan JA. Immunology. 2005 Oct;116(2):145-63.
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
ABSTRACT: Interest in the interactions between nervous and immune systems involved in both pathological and homeostatic mechanisms of host defence has prompted studies of neuroendocrine immune modulation and cytokine involvement in neuropathologies. In this review we concentrate on a distinct area of homeostatic control of both normal and abnormal host defence activity involving the network of peripheral c-fibre nerve fibres. These nerve fibres have long been recognized by dermatologists and gastroenterologists as key players in abnormal inflammatory processes, such as dermatitis and eczema. However, the involvement of nerves can all too easily be regarded as that of isolated elements in a local phenomenon. On the contrary, it is becoming increasingly clear that neural monitoring of host defence activities takes place, and that involvement of central/spinal mechanisms are crucial in the co-ordination of the adaptive response to host challenge. We describe studies demonstrating neural control of host defence and use the specific examples of bone marrow haemopoiesis and contact sensitivity to highlight the role of direct nerve fibre connections in these activities. We propose a host monitoring system that requires interaction between specialized immune cells and nerve fibres distributed throughout the body and that gives rise to both neural and immune memories of prior challenge. While immunological mechanisms alone may be sufficient for local responsiveness to subsequent challenge, data are discussed that implicate the neural memory in co-ordination of host defence across the body, at distinct sites not served by the same nerve fibres, consistent with central nervous mediation. Read more

Mobilisation of specific T cells from lymph nodes in contact sensitivity requires substance P

Andrew J. Shepherda, Lorna J. Beresforda, Eric B. Bellb, Jaleel A. Miyana . Journal of Neuroimmunology Volume 164, Issues 1, Pages 115-123 (July 2005) ABSTRACT: Capsaicin-mediated depletion of neuropeptides in the skin was previously shown to abolish a dinitrocholorobenzene (DNCB)-induced contact sensitivity (CS) response. To understand the basis for this disruption, we explored whether nerve fibres innervating the draining lymph node (LN) could be involved. As expected, removal of the draining LN after DNCB sensitisation abolished the CS response. Furthermore, the CS response could be abolished by destroying the nerve fibres in the draining LN and could be restored by providing the LN with the neuropeptide substance P. The size of the CS response restored by substance P was dose dependent. The response was also inhibited by exposing the lymph node to a neurokinin-1 receptor antagonist which blocks binding of substance P.
The results suggest that an afferent signal from the skin via the sympathetic arm of the central nervous system evokes an efferent signal to the LN which combines to regulate the CS response.  The efferent signal may serve to control or release from the LN primed effector lymphocytes into the circulation.
Read More

The role of epigenetic dysregulation in the epidemic of allergic disease

Susan Prescott & Richard Saffery.  Clin Epigenet (2011) 2:223–232 DOI 10.1007/s13148-011-0028-4. Received: 25 January 2011 / Accepted: 13 March 2011 / Published online: 13 April 2011. ABSTRACT: The epidemic of allergic disease in early life is one of the clearest indicators that the developing immune system is vulnerable to modern environmental changes. A range of environmental exposures epidemiologically associated with allergic disease have been shown to have effects on the foetal immune function in pregnancy, including microbial burden, dietary changes and environmen- tal pollutants. Preliminary studies now suggest that these early effects on immune development may be mediated epigenetically through a variety of processes that collectively modify gene expression and allergic susceptibility and that these effects are potentially heritable across generations. It is also possible that rising rates of maternal allergy, a recognised direct risk factor for infant allergic disease, may be further amplifying the effects of environmental changes. Whilst effective prevention strategies are the ultimate goal in reversing the allergy epidemic, the specific environmental drivers, target genes, and intracellular pathways and mechanisms of early life immune programming are still unclear.  It is  hoped that identifying  genes that  are differentially regulated in association with subsequent allergic disease will assist in identifying causal pathways and upstream contributing environmental factors. In this way, epigenetic paradigms are likely to provide valuable insights into how the early environment can be modified to more favourably drive immune development and reverse the allergic epidemic. Read more