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Clinical and immunological response to oral and subcutaneous immunotherapy with grass pollen extracts. A prospective study.

Forty children allergic to grass pollen were divided into two groups, and matched by their serum IgE antibody concentrations to grasses. For two preseasonal treatment periods one group received immunotherapy with an alum adsorbed grass pollen extract, while the second group was treated orally with an aqueous extract of the same allergens. The patients' postseasonal self evaluation as well as the mean symptom scores calculated from symptom diaries indicate, that oral treatment is significantly less effective in controlling seasonal allergic symptoms than subcutaneous immunotherapy. During oral treatment neither an increase of specific serum IgG antibodies, nor a suppression of the seasonal increase in specific serum IgE antibodies could be demonstrated.

Administration, Oral↗

Hyposensitization in hay fever with grass pollen extracts: a three-year study comparing a dialysed alum adsorbed extract with allpyral.

Immunotherapy with a dialysed aqueous extracted alum absorbed extract of grass pollens and with undialysed pyridine extracted alum precipitated extract of grass pollens (Allpyral) was compared in 58 patients with hay fever over a three year period in a randomized open study. Both types of treatment resulted in similar immunological responses as measured by changes in grass specific serum IgE and IgG. The dialysis of the grass pollen material did not decrease or increase the stimulation of specific immunoglobulins. The incidence of both local and systemic side effects was similar in both treatments. More injection site granulomata occurred in patients treated with the new alum adsorbed extract, although the difference did not achieve statistical significance. Symptom-medication data showed that patients who received the conventional pyridine extracted materials obtained a better clinical response, but all treatments gave continuing clinical benefit in each successive year.

Adolescent↗

[Bronchial asthma in children with sensitization to mites].

Overall 180 children with bronchial asthma induced by sensitization to Dermatophagoides pteronyssinus and Dermatophagoides farinae were examined clinically and immunologically. The patients' age ranged from 1 to 14 years. A relationship was established between bronchial asthma exacerbation and the stay at home. In that disease pattern, asphyxia attacks were noted to occur more frequently in the evening and night hours. Emphasis is laid on the leading part played by the IgE-mediated mechanism in bronchial asthma induced by tick-borne sensitization. In children suffering from that pattern of bronchial asthma, specific hyposensitization with Dermatophagoides pteronyssinus allergens and antiallergic immunoglobulin were found to be highly effective.

Adolescent↗

[Disodium cromoglycat (intal) in the treatment of allergic states of the respiratory system (author's transl)].

Disodium cromoglycate (Intal) has been found several years ago to act as an reliable drug in the treatment of allergic states of the respiratory system. The effective mechanism seems to be its stabilizing function for circulating and sessile mast cells, thus avoiding the release of histamine and other vasoactive amines after an immunological or non-immunological stimulus. Although DSCG does not inhibit the binding of antigen to its antibody it must be given prophylactically before the antigen has access to the mast cells. Most efficiently DSCG is used in the treatment of the exogenous allergic asthma, and secondly in allergic rhinitis (70-90% success). Own observations confirm the effectiveness of the drug especially in patients with pollinosis. In addition it was found that DSCG can be used during hyposensitization procedures and that the drug does not influence the results of skin testing. At present there have been detected neither side-effects nor interactions with other drugs.

Adult↗

Long-term hyposensitization and adverse immunologic responses. A laboratory evaluation.

Ninety atopic patients with allergic asthma and/or rhinitis were classified into three groups: group A, consisting of 30 patients never subjected to immunotherapy; group B, 30 patients receiving immunotherapy for various allergies for 3 to 24 months; group C, 30 patients receiving immunotherapy for 5 or more years. The following studies were performed using standard techniques: quantitative determination of serum immunoglobulin concentrations IgA, IgG, IgM, rheumatoid factor, C3 and C4 concentrations, antinuclear antibodies (ANA). Circulating immune complexes were detected by a competitive immuno-enzyme assay. No statistical differences were found in the groups studied for every parameter considered. Although signs and symptoms of autoimmune disease were not present, an elevated incidence of ANA in the entire group (23.3%) was found.

Adolescent↗

Recombinant allergens.

A great variety of recombinant plant, mite, mold, mammal, and insect allergens have been expressed in heterologous hosts (e.g., Escherichia coli), their cDNA being used as a template. The number of biologically active recombinant allergens available for experimental, diagnostic, and therapeutic purposes is increasing tremendously. Recombinant allergens have proven to be valuable tools to investigate T-cell and B-cell recognition of allergens as well as to study mechanisms of specific IgE regulation. The immunologic equivalence of many relevant recombinant allergens with their natural counterparts has been demonstrated, and the three-dimensional structures of several recombinant allergens have been described recently. As a result of extensive cross-reactivities among the relevant allergens, it appears that the number of epitopes needed for diagnosis and specific immunotherapy is less diverse than originally anticipated and might be soon covered by recombinant molecules. Recombinant allergens have been used for successful in vitro, as well as in vivo, allergy diagnosis, and work is in progress to produce recombinant allergen derivatives with reduced anaphylactic potential to improve current forms of immunotherapy.

Allergens↗

Immunotherapy with partially purified and standardized tree pollen extracts. I. Clinical results from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Fifty-four adult patients with tree pollen-induced rhinitis (28), asthma (1), or rhinitis and asthma (25) were selected for immunotherapy with standardized and partly purified tree pollen extracts using a double blind protocol. The selection was based on clinical history, results of nasal or bronchial challenge, skin prick tests and RAST. Further, based on crossed radio-immunoelectrophoresis, sex, age and severity of symptoms, the patients were allocated in matched pairs and the treatment alternatives were randomly distributed within the pairs. Twenty-three patients treated with extracts composed of any combination of alder, birch and hazel pollen which matched their IgE response in CRIE (Group 1 (ABC)) and 22 patients receiving birch pollen extracts (Group 2 (B)) completed all 3 years of treatment. The in vivo results comprising symptom and medicine consumption scores are given here. Changes in specific skin and nasal reactivity as well as in immunological parameters are presented separately. No significant differences were demonstrated between the treatment groups in the two parameters. Both extracts were effective and reduced in general the symptom scores to one tenth of the starting level. Expressed another way, at the end of the study, the patients tolerated 30 times more pollen until symptoms of the same severity were elicited, compared to before. In the Nordic countries, spring-time asthma and rhino-conjunctivitis caused by pollen from deciduous trees can be effectively treated with an extract of birch pollen alone.

Adolescent↗

[Immunological mechanisms in allergen-specific immunotherapy: impact on future trends in type-1 allergy management].

Specific immunotherapy (SIT) is the only treatment of Type-I allergy that leads to a modulation of the immune response to the eliciting allergen. The repeated administration of high doses of antigen induces a state of "antigen-specific non-responsiveness", i.e. immunologic tolerance to the injected antigen. Accordingly, during and after SIT the proliferative response of allergen-specific T lymphocytes in response to the administered antigen are significantly reduced. According to recent publications, this effect is due to the production of the immunosuppressive cytokine interleukin (IL)-10, which is induced during the treatment. On the other hand, a distinct change in the quality of the immune response to the injected allergen can be observed: the production of the IgE-inducing cytokine IL-4 by T helper cells decreases. Moreover, the release of other proinflammatory cytokines and inflammatory mediators is suppressed. Together, these events result in a marked decrease of symptoms during allergen exposure and reduced reactivity during challenge.

Allergens↗

[Incidence of adverse reactions to immunotherapy in allergic patients at Puebla University Hospital].

MATERIAL AND METHOD: In order to know adverse reaction incidence to, immunotherapy, it realized a longitudinal, prospective and descriptive study in patients of outward consultation of Allergy Immunology Clinic Service of Hospital Universitario de Puebla in a period of 10 months. It determined age, sex, diagnostic, reaction adverse kind and presentation time of them. Initial immunotherapy dose was 0.05 ml administered subcutaneously with treatment antigens 1:100 weight/volume without premedication. It included 170 patients with average age of 22.6 years (SID 15.4), 56.5% female sex and 43.5% male. RESULTS: Most frequent pathologics were asthma and rhinitis. Adverse reactions incidence at specific immunotherapy were 2.4%, all of them were of immediate and local kind. CONCLUSION: These results are influence by the concentration and dose of antigens utilized and may differ of another studies.

Adult↗

Allergen-specific immunotherapy: an update on immunological mechanisms of action.

Specific immunotherapy (SIT) is the only treatment able to modify the natural history of the allergic subjects. Several aspects of the immunopathological response modified by SIT have been investigated; the first parameter historically studied was the production of allergen-specific antibodies. An increase of allergen-specific IgG4 and a decrease of IgE appear after SIT. A shift from Th2-polarized immune response toward Th1-oriented pattern has been reported after SIT. More recently, a crucial role for a subpopulation of T cells has been evidenced: T regulatory cells (Treg). Allergic patients have a defect of Tregs. SIT is able of inducing a specific Treg response. Sublingual immunotherapy is an alternative route of administration for SIT. Recent evidence shows that SLIT is also able of inducing a Treg response as detected by IL-10 production.

Allergens↗

Local immunotherapy in allergy: prospects for the future.

Sublingual immunotherapy in allergy is a promising method invented in its preliminary form almost 100 years ago, but applied in practice for only several years. A continuously increasing number of controlled studies indicate the efficacy of this method, but nevertheless numerous questions concerning immunological mechanisms, mode of application or long-term (side) effects remain to be answered and are responsible for keeping clinicians from prescribing it. Thus far, only a few studies compare the local and subcutaneous application of immunotherapy, but since the most efficient mode of application still remains far from being determined, such comparisons cannot be used for a general or definite recommendation of one of both therapies. The studies also fail to take into consideration patients' compliance or acceptance of different types of therapies depending upon the previous duration and state of allergy. Although the acquiescence of local immunotherapies by physicians and patients is increasing, the topic will continue to offer material for years of emotional and scientific discussions.

Administration, Sublingual↗

Specific immunotherapy in asthma.

There is a growing appreciation of asthma as an inflammatory disease. Immunotherapy may play a role in modulating immunologic responses including inflammatory mediator production from cells involved in asthma. Studies of pollen-sensitive asthma have demonstrated beneficial effects of specific immunotherapy for grass, birch, and ragweed pollen-induced asthma. However, risk of systemic reactions exists, especially when specific immunotherapy is administered during the specific allergen season. House dust mite immunotherapy has benefitted asthmatic children more than adults. Patients having unstable pulmonary function may be at the highest risk of having systemic reactions to such immunotherapy. Animal dander immunotherapy and immunotherapy for molds including Clasdosporium and Alternaria may improve selected asthmatic patients. Avoidance of the offending allergen is still, however, the preferred mode of treatment of allergic asthma.

Adult↗

[Physiological and pathological aspects of the immune reactions (author's transl)].

The basic principles of modern immunology are reviewed. In analogy to the nervous defence mechanism of the body the immune reactions are divided into a "specific" afferent, "unspecific" efferent and central regulatory part. The old conception of the "lock and key" relation between antigen and antibody is re-interpreted in terms of molecular chemistry. The dual aspects of the immune response is interpreted as part of an over-all network within which the humoral and cellular defence systems are organized to act in concert. Allergy is considered to be solely a special type of immune reaction; while its disease-producing effects are undisputed its physiological significance is still obscure. The immune mechanism involved in specific densitization is discussed in detail.

Antibody Formation↗

Immunotherapy by inhalation of allergen in powder in house dust allergic asthma--a double-blind study.

The authors report the analysis of clinical and immunological parameters during local immunotherapy (LI) by inhalation of an extract in powder in patients with allergic asthma due to D. pteronyssinus (DP). The study was double-blind and lasted 24 months. Twenty-four patients were randomly assigned on a double-blind basis to receive by inhalation increasing doses of a micronized, freeze-dried DP extract in powder (14 patients, active therapy) or capsules of lactose (10 patients, placebo group). Results showed a statistically lower symptom score, a significant increase in bronchial tolerance to the allergen and significant levels of DP-specific IgG in actively treated patients compared to those treated with placebo.

Administration, Inhalation↗

Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides.

BACKGROUND: Allergen specific immunotherapy was known to be useful in the treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT) offers advantages such as a good efficacy/safety ratio and a more convenient allergen delivery. The aim of this study was to assess the safety and clinical efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo controlled study carried out for two years, with a modified schedule of LNIT treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a maintenance period at low dosage (80 AU) once a week. Symptom and medication scores. threshold dose with specific nasal provocation test (NPT) and immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important local or systemic side-effects were observed in children who completed the study. Compared to placebo, the active treatment group showed significant improvement in rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT. These results were confirmed by a significant reduction of allergen specific nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of low-dose LNIT suggests that this therapy may be useful in the treatment of allergic rhinitis disease in children.

Administration, Intranasal↗

[Specific immunotherapy for respiratory allergies. A modern treatment].

UNLABELLED: AN EFFICIENT AETIOLOGICAL TREATMENT: Specific immunotherapy or allergen vaccination currently constitutes the only aetiological treatment for allergic respiratory diseases and is more effective in children than in adults. Since its introduction in 1911, it has been much disparaged in spite of its effectiveness demonstrated in double blind placebo controlled studies, for the treatment of both allergic rhinoconjunctivitis and stable and controlled asthma. MECHANISM OF ACTION: Its mechanism of action varies depending on the type of allergen (venoms or pneumallergenes) and its administration route (subcutaneous or local) and recent studies indicate that the prevalent mechanism proceeds from a modification of the T cell response by an immunological deviation (stimulation of the Th0/Th1 lymphocytes) or T lymphocyte anergy (reduction in Th0/Th2) or both at same time. The IL-10, immunosuppressive cytokine secreted by the third population of T-Tr1 lymphocytes, would have an important role. IN PRACTICE: The indications for specific immunotherapy have been specified in international consensuses, and its practical administration must respect preconditions and a certain number of rules. Improvement in quality of allergenic extracts by standardization, better knowledge of its mechanism of action and the availability of local administration routes reinforce its place in the global therapeutic strategy for the management of respiratory allergies. A greater use of the sublingual route, together with biological and clinical research will allow the widening of its indications.

Allergens↗

Topical nasal immunotherapy. Immunologic response of IgE in nasal secretion after immunotherapy with Dermatophagoides pteronyssinus.

We studied 9 children between 9 and 14 years old who had been diagnosed with exclusive allergic rhinitis and were sensitive to acari. Topical nasal immunotherapy for D. pteronyssinus was carried out for 2 years. The total IgE in nasal secretions measured before immunotherapy showed levels of 14.2 to 85.2 IU/ml, and the specific IgE in nasal secretion against D. pteronyssinus and D. farinae ranged from 0.6 to 8.86 PRU (classes II and III). After the immunotherapy the total IgE in nasal secretion fell in 8 of the 9 children (average 24.2 IU/ml. Range 5.6 to 53.3 IU/ml). The specific IgE against D. pteronyssinus rose in 6 children and fell in 3, and all but one of the children remained in class II-III. The tolerance to the immunotherapy was good in all the children.

Administration, Intranasal↗

Clinical and immunological effects of immunotherapy with glutaraldehyde modified house dust mite extract.

The aim of this study was to demonstrate the clinical effectiveness of treatment with specific immunotherapy using allergenic mite extracts modified with glutaraldehyde. The results showed an improvement both in clinical symptoms and a reduction in the complementary pharmacological therapy used. Several clinical "in vitro" and "in vivo" parameters were analysed during this study. The results obtained from the Nasal Challenge Test and the Skin Test (prick-test) were the most relevant. Patient tolerance to the diagnostic extract was increased in 45% of the patients, the result of which was registered in the Nasal Challenge Test. Evaluation of the results derived from the skin tests on conclusion of immunotherapy, showed a reduction in response in 55% of the patients. Progressive immunotherapeutic doses were applied at short intervals with no record of severe reactions.

Adolescent↗