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PubMed1964

THE TREATMENT OF ALLERGIC RHINITIS.

Allergic inflammation of the nasal mucous membranes, like other atopic disorders, occurs primarily as the result of an antigenantibody reaction between external allergens and circulating skin-sensitizing antibodies. In addition, the disease process is frequently complicated by bacterial or viral infection. Effective treatment of allergic rhinitis, therefore, consists of: (1) changing the patient's environment in order to remove the offending allergens, (2) removing the patient from his environment, (3) altering the patient's response to environmental allergens by means of hyposensitization injections, (4) suppressing the allergic reaction with drugs, and (5) eliminating bacterial infection. Usually more than one of these therapeutic measures is required for the individual patient.

Allergens↗
PubMed1981

Cutaneous responses to tests with influenza vaccines.

Responses to the intracutaneous infection of influenza vaccines were examined at 24 and 48 hours. Whole virus and subunit virus vaccines of comparable potency induced local reactions of comparable magnitude. Cutaneous reactions to the influenza vaccines were present in almost all adults but absent in young children. Reactions were greatly reduced by ingested prednisone. Responses to a subunit commercial trivalent influenza vaccine were compared with responses to tuberculin in tuberculin-sensitive subjects. In each subject the tuberculin reaction had greater duration than the influenza reaction. In separate tuberculin-sensitive individuals the flu vaccine and tuberculin reactions were biopsied at 24 hours. There was mild to moderate cellularity in the responses to both reactants. The cellular infiltration was mainly mononuclear cells except in one case in whom both agents elicited an infiltrate in which neutrophils and eosinophils predominated. The microscopic findings in reactions to tuberculin and influenza vaccine were comparable. Immunofluorescence studies revealed the deposition of complement (C3) in most reactions and of immunoglobulin (particularly IgM) in some reactions of both types. The findings support the view that local reactions to influenza vaccines are acquired and probably immunologic; the difference in duration from tuberculin reactions points to a different pathogenesis which is not yet entirely characterized.

Adult↗
PubMed1993

Immunotherapy for respiratory allergic diseases: indications, efficacy and monitoring.

The author reports a detailed analysis of the indications for Specific Immuno-Therapy (SIT) in allergic rhinitis and asthma. After pointing out the requirements for a correct clinical trial, the efficacy of SIT towards various allergenic agents is examined (pollen, mites, cat and dog danders, moulds). Clinical monitoring--by means of clinical diaries, symptom score, drug consumption, skin tests, challenge tests--and immunological monitoring--by means of measuring of IgE and IgG serum antibodies, mediator and cytokine release, lymphocyte study, etc.--are then discussed. Immunological and clinical parameters to evaluate the efficacy of SIT are compared: clinical parameters being the most effective means of evaluation of clinical improvement.

Allergens↗
PubMed2005

Peptide-based therapeutic vaccines for allergic and autoimmune diseases.

Allergic and autoimmune diseases are forms of immune hypersensitivity that increasingly cause chronic ill health. Most current therapies treat symptoms rather than addressing underlying immunological mechanisms. The ability to modify antigen-specific pathogenic responses by therapeutic vaccination offers the prospect of targeted therapy resulting in long-term clinical improvement without nonspecific immune suppression. Examples of specific immune modulation can be found in nature and in established forms of immune desensitization. Understanding and exploiting common mechanisms such as the ability to induce antigen-specific regulatory cells should allow the development of effective therapeutic strategies for both forms of immunopathology. Targeting pathogenic T cells using vaccines consisting of synthetic peptides representing T cell epitopes is one such strategy that is currently being evaluated with encouraging results. Future challenges in the development of therapeutic vaccines include selection of appropriate antigens and peptides, optimization of peptide dose and route of administration and identifying strategies to induce bystander suppression.

Antigen-Presenting Cells↗
PubMed2006

Sublingual immunotherapy induces spirometric improvement associated with IL-10 production: preliminary reports.

BACKGROUND: Sublingual immunotherapy (SLIT) has been demonstrated to be able of inducing immunologic changes as evidenced by IL-10 production. Forced expiratory flow between 25% and 75% of the vital capacity (FEF(25-75)) may be considered a good marker of early bronchial involvement in patients with pure allergic rhinitis. OBJECTIVE: The aim of this study was to evaluate the possible association of IL-10 production with FEF(25-75) values in patients with perennial allergic rhinitis (PAR) successfully treated with SLIT. METHODS: 19 patients with PAR were studied: 9 successfully assumed SLIT for 3 years, 10 were considered as control. In vitro IL-10 production was evaluated after SLIT. Spirometry and bronchodilation test were performed in all subjects at baseline and after 3 years. RESULTS: After 3 years, FEF(25-75) values significantly (p=0.0131) increased in SLIT group (80.5+/-6.7), whereas they significantly (p=0.0021) decreased in non-treated patients (60.8+/-2.62). In addition, SLIT-induced increase of FEF(25-75) values is significantly associated with IL-10 production (p=0.0025). CONCLUSIONS: This study provides the first evidence that SLIT is capable of improving early bronchial involvement in patients with pure allergic rhinitis and this functional effect may be associated with immunological changes, such as the induction of IL-10 production.

Administration, Sublingual↗
PubMedDate not supplied

[Asthma: prevalence, pathogenesis and perspectives on new treatments].

Asthma is a complex clinical syndrome with many phenotypes in both children and adults. Its major characteristics include airway inflammation and obstruction, bronchial hyper-responsiveness. The disease has its roots in infancy, and both genetic and environmental factors contribute to its inception and clinical evolution. The prevalence of asthma in increasing around the world. Hypotheses that attempt to explain the rising prevalence have been advanced but remain unproven. To understand its pathogenesis it is essential to identify factors that modulate or intensify the inflammatory response of the airways. The association of allergic asthma with immune responses mediated by TH-2 cells and IgE antibodies has came to the forefront of medical research. Significant advances in understanding the immunology of asthma are being translated into specific therapies, some of which hold promise for disease modification.

Adolescent↗
PubMed1991

Blocking antibodies to inhalant allergens and asthma.

The mechanisms of specific immunotherapy are not still established. Among the lot of immunological changes, induced by immunotherapy, the increase of specific IgG 1, and then of IgG 4 antibodies, during the first months is well demonstrated. The skin-tests, the histamine-release and the human basophil degranulation are significantly decreased after incubation of allergen with the serum of desensitized patients. This antigen neutralizing capacity (blocking antibodies) disappeared when IgG 4 were suppressed from the serum by the mean of activated columns linked either with allergen, or protein A or antihuman IgG4 antibodies. Conversely, the total amount of serum blocking activity was found using pure IgG 4. However, the role of IgG 4 antibodies remains a subject of controversy. Since a clear correlation has yet to be established with symptom scores.

Allergens↗
PubMed2005

Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus.

BACKGROUND: The conventional schedule for subcutaneous immunotherapy with allergen extracts, although efficacious and safe, is slow during the dose-increase phase. OBJECTIVE: We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase. METHODS: Of 239 patients with rhinitis, allergic bronchial asthma, or both caused by D pteronyssinus , 120 were randomly assigned to the cluster schedule, and 119 were randomly assigned to the conventional schedule. A biologically standardized D pteronyssinus depot extract (ALK-Abelló S.A., Madrid, Spain) was administered in a placebo-controlled, double-blind fashion during the initial phase of cluster or conventional treatment. We recorded adverse reactions, clinical efficacy, cutaneous reactivity, and serum specific immunoglobulins to D pteronyssinus before immunotherapy, when the maximum dose was reached in the cluster and conventional schedules, and after 1 year of treatment. RESULTS: The cluster schedule reduced the time to maintenance dose by 46% and caused systemic adverse reactions (all mild) after only 0.15% of injections, with no differences in comparison with the conventional schedule. Cluster immunotherapy led to decreases in asthma and rhinitis symptoms, reduced the cutaneous reactivity, and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week, 6 weeks earlier than with the conventional schedule. CONCLUSION: The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner.

Adolescent↗
PubMed2003

Safety of allergen-specific sublingual immunotherapy and nasal immunotherapy.

Allergen-specific immunotherapy is a well-established treatment for respiratory allergy. It is usually administered subcutaneously, and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel routes of administration (local routes) were developed. Sublingual and local nasal immunotherapy are now considered as viable alternatives to the injection route, mainly due to their optimal safety. The use of nasal immunotherapy is at present declining. On the other hand, sublingual immunotherapy was investigated in twenty-two randomized controlled trials and two postmarketing surveys: its safety profile turned out to be satisfactory in both adults and children, gastrointestinal complaints being the most frequently reported side effects. These side effects were always mild and could be treated with proper dose adjusting. At variance with injection immunotherapy, no severe systemic adverse event has ever been described. Its safety is also supported by pharmacokinetics and immunological data. Experimental data on the safety of sublingual and nasal immunotherapy will be reviewed.

Administration, Intranasal↗
PubMed2006

What do we need to learn to optimize the SLIT alternative?

Allergen-specific immunotherapy (IT) is the only treatment of allergy in adults and children capable of modifying the immune response at early steps. As a consequence, IT improves symptoms, prevents the onset of new sensitizations, reduces the risk of developing asthma and its clinical efficacy lasts many years. The main rationale for administering sublingually IT (SLIT) is to reduce the occurrence of side effects, still yet preserving the immunological effects. SLIT with the most common allergens have been used in many studies with significant clinical effectiveness in both asthma and rhinitis. The pharmacokinetic of allergens administered through non injection routes is complex. Peptide absorption across oral mucosa occurs mainly by passive diffusion but delivery of proteins has some limitations. Moreover, the molecular mechanisms responsible for the efficacy of SLIT are poorly defined. In this review we focus on the anatomy/histology of the oral cavity as well as on the associated immunological structures to envisage what may happen when an allergen is kept in the mouth. Moreover, the induction of immune responses in this particular immunological environment is also discussed.

Administration, Sublingual↗
PubMed1993

[Molecular and functional characterization of allergens: fundamental and practical aspects].

Well-defined allergens are a prerequisite for the exact diagnosis and immunotherapy of Type I (IgE-mediated) allergic diseases. The allergens have to be available in highly purified form and in sufficient quantities. By applying molecular cloning methods this goal can be achieved with respect to both characterization and reproducibility of allergen preparations. Moreover, this technique leads to the deduction of primary structures of allergens, which allows computer-aided comparisons with already known amino acid sequences. Significant sequence similarities with well-described proteins may point to a biological and biochemical function of the cloned allergen. The major allergen of white birch, Bet v 1, and its close relatives from alder, hazel, and hornbeam belong to a family of pathogenesis-related proteins ubiquitous in angiosperms. Based on these results, a percentage of food intolerance can now be regarded as Type I allergy due to Bet v 1-related proteins. By sequence comparisons, Bet v 2, another birch pollen allergen, was identified as the ubiquitous cytoskeleton-associated protein, profilin. For its high sequence conservation and its ubiquitous appearance in allergenic sources of plant origin, profilin was shown to represent a pan-allergen. Recombinant non-fusion Bet v 1 revealed identical immunological properties with respect to interaction with both antibodies and Bet v 1-specific T cell clones when compared with natural Bet v 1 purified from birch pollen.

Allergens↗