Sublingual Specific Immunotherapy Research Articles

Allergen specific immunotherapy for atopic dermatitis

To describe recent developments as well as the pros and cons of allergen specific immunotherapy as a putative therapeutic option for a subgroup of patients with atopic dermatitis. The question whether specific immunotherapy would impair or improve the severity and course of atopic dermatitis has been a matter of debate for a long time. Double-blind placebo-controlled studies on the safety and efficacy of subcutaneous and sublingual specific immunotherapy in atopic dermatitis are rare; however, a systematic review of the literature on all published studies on specific immunotherapy in atopic dermatitis, together with the results of the most recent controlled studies, provides promising results. The review discusses developments and recent advances in the field of specific immunotherapy as a causal therapy of sensitizations in atopic dermatitis. The most promising approaches, outlining putative immunologic as well as clinical changes which might go along with specific immunotherapy in atopic dermatitis patients, are highlighted. Further, we discuss how upcoming clinical studies and research could help to open new avenues for specific immunotherapy as a treatment for atopic dermatitis in the near future.

Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children

The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T (Grazax, ALK-Abelló A/S, Hørsholm, Denmark) in children aged 5-12 yr. The study was randomized, double-blinded and placebo-controlled. Sixty children aged 5-12 yr suffering from grass pollen-induced rhinoconjunctivitis (with or without asthma) from five centres in two countries (three in Germany and two in Spain) participated in the study. They were randomized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season. A total of 810 treatment-related adverse events were reported in the Grazax group. The majority of these were local reactions in the mouth or throat and were mostly mild (71%) to moderate (27%) in severity and resolved within days. Thirty-five (78%) subjects treated with Grazax and five (33%) treated with placebo reported at least one treatment-related adverse event. Oral pruritus, throat irritation, mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events. 62% (28 of 45) of the actively treated subjects reported oral pruritus, 36% (16 of 45) throat irritation, 31% (14 of 45) mouth oedema and 22% (10 of 45) ear pruritus. Two actively treated subjects withdrew from the study: one subject due to four adverse events (moderate eye pruritus, moderate pharyngolaryngeal pain, moderate non-cardiac chest pain and moderate dysphagia) and one subject due to a serious adverse event (asthmatic attack). The subjects recovered completely from the events. In conclusion, in the present study, Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children.

Sublingual Specific Immunotherapy: State of the Art

Sublingual immunotherapy (SLIT) was first attempted more than a century ago. After a long parenthesis probably related to the lack of impressive clinical results, the advances on allergen quantification and characterization, together with the improvements in the recombination techniques have renewed the interest in this therapy during the past decade. There are currently enough high quality clinical trials on its efficacy in the management of respiratory allergies (asthma and rhinoconjunctivitis) to conclude that SLIT could be an effective tool for the management of those diseases. This effectiveness has been shown both in children and in adults. However, while there are some clues related to the mechanism of action of SLIT, there is still much to know about it. In addition, more studies comparing the effectiveness of SLIT vs the standard subcutaneous immunotherapy (SCIT) are needed to definitely establish the role of SLIT in the treatment of allergic diseases. SLIT has proven a very safe therapy as compared to SCIT, a fact which adds a very important advantage to the sublingual route.

New perspectives in the treatment of allergic rhinitis and asthma in children

Allergic rhinitis and asthma are some of the most prevalent chronic diseases in children. Meticulous evaluations of the therapeutic options and interventions are needed to control this burden. The central pathogenic mechanism is an immediate hypersensitivity reaction, followed by interventions in the allergic cascade. Once inflammation is established, potent anti-inflammatory agents or mediator antagonists could help control the phenomenon and reduce the characteristic symptoms related to severity. Monoclonal antibody against IgE has demonstrated its efficacy in reducing the symptoms of asthma and rhinitis. In difficult-to-treat asthma patients it allows a reduction in the dose of inhaled steroids, the number of exacerbations, emergency visits and hospitalizations. Its broad implementation is limited by its high cost because adverse events are not a concern. Specific sublingual immunotherapy gave promising results in clinical trials, while modifying immunoglobulins and cytokine profiles, also inducing T-cell tolerance. Safety issues of subcutaneous immunotherapy have been surpassed by the sublingual route, with equivalent efficacy. The new inhaled steroid ciclesonide is effective in established inflammation, is activated only in the respiratory system, and has negligible systemic effects. Robust evidence on the efficacy and safety of several novel therapies in rhinitis and asthma is available.

Cost-Effectiveness of Sublingual Specific Immuno-Therapy Versus Current Symptomatic Treatments in Adults with Allergic Rhinitis and Asthma, in the Societal Perspective

Cost-Effectiveness of Sublingual Specific Immuno-Therapy Versus Current Symptomatic Treatments in Adults with Allergic Rhinitis and Asthma, in the Societal Perspective

Absence of systemic immunologic changes during dose build‐up phase and early maintenance period in effective specific sublingual immunotherapy in children

Sublingual immunotherapy (SLIT) has been reported to be a safe treatment for inhalant allergies in children. Yet the immunologic mechanisms resulting in clinical improvement are poorly understood. To identify early systemic immunologic changes during the first 8 weeks of clinically effective SLIT to grass pollen, tree pollen or house dust mite in paediatric patients with allergic rhinoconjunctivitis and/or asthma. Peripheral blood mononuclear cells and plasma samples of 13 children with reduced symptoms after 1 year of SLIT were obtained before therapy and at 2 and 8 weeks after the initiation of SLIT. Allergen-specific lymphocyte proliferation assays were performed, and allergen-induced cytokine production (IL-2, IL-4, IL-10, IFN-gamma, and TGF-beta(1)) was measured by ELISA and flow cytometry. Allergen-specific IgE, IgG1, IgG4, and IgA levels in plasma samples were determined in ELISA. During the first 8 weeks of successful SLIT, allergen-specific lymphoproliferation (n=13) as well as levels of allergen-specific intracellular (n=8) and secreted cytokines (n=9) did not change significantly. In addition, no alterations in levels of allergen-specific Igs (n=7) were observed. We could not find any early systemic immunologic changes during the first 8 weeks of clinically effective SLIT to inhalant allergens in paediatric patients with allergic rhinoconjunctivitis and/or asthma.

Sublingual rush immunotherapy with latex extract in children

Abstract Latex allergy prevalence has increased notably in the last two decades. Latex ubiquity and its cross-reactivity with fruits make complete avoidance difficult to attain and studies have questioned long-term avoidance efficacy. Subcutaneous and sublingual routes of specific immunotherapy (SIT) to latex have been tested in double blind placebo controlled studies, with significant improvement in patients' tolerance to latex. We present our experience with a sublingual desensitization protocol in three latex allergic children. The build-up phase consisted of rush, with daily admission for 4 consecutive days, followed by a maintenance period at home. Only local reactions, with good response to antihistamines were observed during rush and no reactions have been reported with maintenance dose during 6, 5 and 2 months, respectively. The first patient has accomplished 6 months maintenance treatment. Allergological re-evaluation has shown a decrease in skin reactivity and serum specific IgEs to latex and cross-reactive fruits. Comparison of the results of specific IgEs measurement to a panel of latex recombinant allergens before rush and 6 months later clearly showed a decrease in Hev b 5 and Hev b 6.01, with no other detectable new sensitizations. Immunoblot was also performed before rush and 6 months later and shows a decrease in sensitization without appearance of new bands. Future enlargement of our series and prospective follow-up will help to clarify the real clinical efficacy of sublingual SIT. As this is a safe and easy to use protocol, it seems to be specially appropriate for children.

Sublingual specific immunotherapy for adults and children: a post-marketing surveillance study

Sublingual specific immunotherapy for adults and children: a post-marketing surveillance study

Sublingual specific immunotherapy for adults and children: a post-marketing surveillance study

BackgroundSublingual immunotherapy (SLIT) is a relatively new form of treatment for type I allergies nd a good safety profile is rapidly being established. Evidence on the efficacy of SLIT is increasing, and the present study provides further supportive data. We describe the results of treatment with a SLIT vaccine formulated with a range of allergen extracts obtained by allergologists in daily clinical practice MethodsAdult and child patients (n = 159, 81 males, 78 females) with confirmed type I allergic sensitivities were treated with a standardized SLIT vaccine (ORALVAC) using the sublingual-swallow method. Evaluation of the efficacy of SLIT was based on the consumption of anti-allergic medication and a global assessment. Tolerability assessment was based on the incidence of local or systemic reactions ResultsMedication use was significantly reduced compared with that in previous years (p = 0.023). In a large subgroup of patients treated for pollen sensitivity the significance was stronger (p = 0.016). Global assessment revealed that only 3.5 % of patients showed no change in symptoms after therapy. High tolerability was achieved and no serious or severe adverse effects were observed ConclusionOver a one-year period, adult and child patients with a variety of type I allergies were treated with a SLIT vaccine that has shown significant efficacy and was well-tolerated with no serious or severe adverse events

CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation

There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation.

Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an extract of Cupressus arizonica. A double blind study

non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy. We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy (SLIT) in patient with Cupressaceae pollen respiratory allergy. twenty patients with Cupressaceae pollen (C. sempervirens) rhinoconjunctivitis, mild asthma or both were randomly chosen for sublingual immunotherapy (10 patients) or placebo treatment (10 patients) using a double blind placebo controlled technique. We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens. The patients underwent treatment for 12 months (from april 1999 to april 2000). Symptoms and drug scores as well as nasal provocation tests were recorded. The pollen counts were carried out, during all the same period. we found significantly lower symptom scores (p < 0.05) and drug consumption scores (p < 0.05) in the immunotherapy group than in the placebo group, during the pollen season, after the first year of therapy. Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group (p < 0.01). No untoward reactions have been observed. SLIT with Cupressus arizonica (pollen extracts) produced, after one year treatment, a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity. SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy.

Efficiency of sublingual specific immunotherapy in children with bronchial asthma and preasthma

The efficiency of sublingual specific immunotherapy with everyday allergens of 112 children with respiratory allergoses bronchial asthma and preasthma is studied. Its high efficiency is shown: persistant clinical remission of the disease is achieved in 88,4% of the children accompanied by the decrease of sensitization and hypersensitivity of the organ pertaining to shock to allergens and normalization of bronchial permeability.