Subcutaneous Specific Immunotherapy Research Articles

Clinical Improvement and Laboratory Changes in 23 Adolescent Patients with Atopic Dermatitis Undergoing Subcutaneous Specific Immunotherapy with House Dust Mite Allergens

Clinical Improvement and Laboratory Changes in 23 Adolescent Patients with Atopic Dermatitis Undergoing Subcutaneous Specific Immunotherapy with House Dust Mite Allergens

High Serum Tryptophan Concentration in Pollinosis Patients Is Associated with Unresponsiveness to Pollen Extract Therapy

Background/Aims: The immunologic background of allergic asthma and rhinitis includes a preponderance of Th2-type immunity. In parallel, Th1-type immune response is suppressed by Th2-type cytokines. As a consequence, biochemical pathways triggered by Th1-type cytokine interferon-γ, such as tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin production, might be altered. We examined whether they are related to the outcome of hyposensitization therapy in atopic patients. Methods: In serum specimens of 44 atopic patients (18 women, 26 men) before any specific immunotherapy, tryptophan and kynurenine concentrations were measured by HPLC, and the kynurenine to tryptophan ratio (kyn/trp) was calculated. Neopterin concentrations were measured by ELISA. Results were compared with concentrations in 38 serum specimens from healthy blood donors and with the outcome of specific subcutaneous immunotherapy in atopics: on clinical grounds, 27 patients were classified as responders, and 17 patients as non-responders. Results: Serum tryptophan concentrations were higher in atopics (84.3 ± 24.4 µM) than in blood donors (57.9 ± 7.46 µM; p < 0.001), kynurenine and kyn/trp were not different between the 2 groups. All of the neopterin concentrations measured in patients were <8.7 nM, the upper limit of the normal. Non-responders to subcutaneous immunotherapy had significantly higher tryptophan concentrations (95.7 ± 27.0 µM) than responders (77.1 ± 19.9 µM; p = 0.01). No other marker concentrations differed between the groups. Conclusions: The measurement of serum tryptophan may present an option to predict the outcome of pollen extract therapy. Higher tryptophan levels may result from lower indoleamine 2,3-dioxygenase activity in atopics. However, this possible relationship needs to be confirmed in further studies.

Effect of house dust mite immunotherapy on transforming growth factor β1-producing T cells in asthmatic children

Recent evidence suggests that regulatory T cells (Treg cells) and immunosuppressive cytokines, such as transforming growth factor BETA1 (TGF-BETA1) and interleukin 10 (IL-10), may have a role in clinically effective allergen specific immunotherapy (SIT). To evaluate the effect of SIT on the induction of Treg cells in house dust mite-allergic children and on the expression of specific Treg cell markers (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], IL-10, and TGF-BETA1). In this uncontrolled open-label study, the percentage of peripheral blood CD4+ Treg cells (CD69 CD45RO+CTLA-4+ and CD3+CD4+CD25+FOXP3+) and the expression of molecules associated with their functions (CTLA-4, TGF-BETA1, and IL-10) were analyzed using flow cytometry in 16 children allergic to house dust mites before and at 3 and 12 months of subcutaneous SIT. Clinical variables, such as symptom score, medication requirements, forced expiratory volume in 1 second, peak expiratory flow rate, and serum IgE levels, were also determined. Ten healthy children were included as controls. All the clinical variables improved during immunotherapy. The percentage of CD4+CD25+CD69-CD45RO+ Treg cells remained unchanged. The percentage of CTLA-4+ -expressing Treg cells transiently increased after 3 months of immunotherapy, whereas the percentage of FOXP3+ Treg cells did not change after 1 year of immunotherapy. Levels of IL-10+ cells transiently decreased after 3 months of immunotherapy. Four children who required inhaled fluticasone propionate administration for significant symptom worsening had no statistically significant increase in TGF-BETA1-secreting T cells at 12 months of SIT, in contrast to 12 children without inhaled corticosteroid treatment. The increase in TGF-BETA1-positive T cells only in children without significant symptom worsening requiring inhaled corticosteroid treatment limits the usefulness of TGF-BETA1 in monitoring response to allergen immunotherapy.

Sublingual immunotherapy induces IL-10–producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation

The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells. We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT. Proliferation of PBMCs and PBMCs depleted of CD25(+) cells obtained from 9 patients before, after 4 weeks, and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated. After 4 weeks, higher frequencies of circulating CD4(+)CD25(+) T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-gamma mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25(+) cells or addition of anti-IL-10 antibodies. After 52 weeks, proliferation in response to Mal d 1 or tetanus toxoid returned to pre-SLIT levels, whereas Bet v 1-induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25(+) cells nor addition of anti-IL-10 antibodies. In parallel, increased IFN-gamma and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-beta levels nor cell-cell contact-mediated suppression of CD4(+)CD25(+) cells changed during the course of SLIT. SLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy. SLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.

Specific immunotherapy has long‐term preventive effect of seasonal and perennial asthma: 10‐year follow‐up on the PAT study

3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. One hundred and forty-seven subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation. The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1-5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) in favor of SIT. A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.

Allergen vaccine for moderate and severe allergic asthmatics

Evaluation of : Blumberga G, Groes L, Haugaard L, Dahl R. Steroid-sparing effect of subcutaneous SQ-standardised specific immunotherapy in moderate and severe house dust mite allergic asthmatics. Allergy 61(7), 843–848 (2006).The prevalence of allergic disorders, such as asthma, has increased worldwide. Indoor allergen exposures were positively associated with persistent respiratory symptoms. Allergen vaccine is recommended as a therapeutic vaccine for allergic diseases. Asthmatics need inhaled corticosteroids to reduce symptoms, but this increases the risk of side effects. The paper under evaluation offers a steroid-sparing effect of subcutaneous standardized quality-standardized specific immunotherapy in house dust mite allergic asthmatics. This study was finished in allergic asthmatics with a double-blind, placebo-controlled study.

Allergen injection immunotherapy for seasonal allergic rhinitis

Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease. To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006. All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo. Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events. We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities. This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

A 3-year Course of Subcutaneous Specific Immunotherapy Results in Long-term Prevention of Asthma in Children. Ten Year Follow-up on the PAT-Study

A 3-year Course of Subcutaneous Specific Immunotherapy Results in Long-term Prevention of Asthma in Children. Ten Year Follow-up on the PAT-Study

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi‐centre, randomized, dose–response study

The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Safety of a SQ‐standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo‐controlled trial

Sublingual treatment of grass pollen induced rhinoconjunctivitis might provide easier access to specific immunotherapy (SIT) and minimize the risk of serious adverse events (AEs) compared to subcutaneous SIT. To identify a safe dose range for once-daily administration of a grass allergen tablet in participants with grass pollen induced seasonal rhinoconjunctivitis. A randomized, double blind, placebo-controlled Phase I trial was conducted outside the grass pollen season. Seven dosage groups [25,000, 75,000, 150,000, 300,000, 500,000, 750,000, or 1,000,000 standardized quality tablet (SQ-T)], consisting of 12 participants randomized either to active treatment or placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at intervals of approximately 1 week to allow for intermittent safety reviews. The grass allergen tablet did not cause any serious, systemic or significant (leading to withdrawal) AEs. The overall incidence of AEs was 74% (1,013 events); all of mild or moderate intensity and most considered treatment-related. The most frequently reported treatment-related AEs, including irritation of the throat, and itching sensations in the mouth and ears, increased with dose. These were primarily mild in intensity, started shortly after medication intake and lasted for minutes to a few hours maximum. Objective oral findings were also dose-dependent. No clinically significant observations were found in safety laboratory, vital signs and 12-lead ECG. A sublingual grass allergen tablet in doses up to 1,000,000 SQ-T daily caused no serious or systemic AEs displaying a safety profile that allows further investigation as once-daily self-medication.

Asthma bronchiale bei Kindern und Jugendlichen

Asthma is characterized by variable bronchial obstruction and bronchial hyperreactivity associated with chronic inflammation in which eosinophils, mast cells, macrophages, epithelial cells, fibroblasts and smooth muscle cells are involved and activated. Hyperreactivity is manifested by coughing or dyspnea induced by allergens, nonspecific stimuli (i.e. cold air, dust, tobacco smoke) and respiratory tract infection. Diagnosis is based on careful medical history with respect to bronchial hyperreactivity, on clinical findings including wheezing at forced long expiration manoeuvres, on lung function tests, and on allergen testing. An asthma attack requires oxygen insufflation, stronger inhaled or even systemic bronchodilation, and a high-dose systemic anti-inflammatory therapy. Long-term asthma therapy aims at a symptom-free course of the disease, which cannot be achieved in all patients, and at the prevention of chronic inflammation which results in an irreversible remodeling process. Drug treatment is performed according to evidence-based guidelines with increasing extent in 4 steps (I - IV). In persisting asthma (II - IV), inhaled corticosteroids are an essential component of asthma therapy. Subcutaneous specific immunotherapy is recommended if an allergen is clinically relevant and cannot be avoided. Patients with house dust mite allergy benefit from encasing of pillow and mattress. In children older than 12 years with severe allergic asthma, treatment with recombinant humanized anti-IgE antibody is a new option. A continuing individual education of all patients and parents is essential to establish correct disease management for all patients. If there is no satisfactory stabilization, a careful differential diagnosis is required using various lung function tests, recently developed techniques for the diagnosis of cystic fibrosis (e.g. measuring nasal potential difference to evaluate the trasnsepithelial chloride transport, complete mutation analysis of the cystic fibrosis gene) and, if necessary, bronchoscopy to exclude foreign body aspiration etc. In addition, pulmonary rehabilitation, including group education, should be attained by means of validated rehabilitation hospitals.

Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report

Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin 10 (IL-10) plays a crucial role in inducing allergen-specific tolerance; however, no previous studies have examined IL-10 production after sublingual immunotherapy (SLIT). To evaluate T-cell proliferation and IL-10 production in patients successfully treated with SLIT for house dust mites (HDMs). Peripheral blood mononuclear cells were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic patients and healthy control subjects. After 3 and 6 days of in vitro stimulation with phytohemagglutinin (PHA), Candida albicans, and Dermatophagoides farinae, proliferation and production of IL-10 were measured. Patients treated with SLIT showed a significant reduction of proliferation induced by C albicans compared with untreated atopic patients (P < .001), but a significant reduction was also demonstrated in healthy controls compared with untreated atopic patients (P < .001). Patients treated with SLIT also showed a significant increase of IL-10 production after Candida and PHA stimuli compared with patients with untreated rhinitis (P < .001 for both). Patients with untreated rhinitis did not produce IL-10. This preliminary study confirms reduced T-cell proliferation and preliminarily provides the first evidence, to our knowledge, of peripheral IL-10 production in allergic patients successfully treated with HDM SLIT.

Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

Background: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children. Methods: We assessed the proliferation of peripheral blood mononuclear cells (³H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)γ and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNγ, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed. Results: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNγ secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNγ secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups. Conclusion: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions.

Health-Economic Analyses of subcutaneous Specific Immunotherapy for grass pollen and mite allergy

Objective To investigate the health and monetary consequences of treating allergy with specific immunotherapy (SIT) compared with symptomatic treatment/standard care among patients with grass pollen or mite allergy. Methods We performed an economic analysis based on 253 grass- and/or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit, Aarhus University Hospital and at a specialist practice in Aarhus. Relevant data were collected before, during and after SIT treatment from the national health service based on each patient's personal identification number and medical records and from a specifically designed questionnaire. A cost-benefit analysis including direct and indirect costs before, during and after SIT was performed. In addition direct costs were related to the clinical effect (improvement in well-being) in the form of a cost-effectiveness analysis. Results The direct cost per patient/year before SIT (equivalent to standard care) was DKK 2,580. The investment in SIT was DKK 27,545 (in present values) per patient over a 4-year period. After SIT the cost was reduced to DKK 1,072 per patient/year. In the long term, prospective introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/ year of improved well-being. However, when indirect costs were included in the economic evaluation SIT was shown to be net beneficial. Conclusion This study reveals that SIT is associated with initial resource investments and subsequent resource savings in the long term compared with standard care. When all consequences are measured in monetary terms, and assuming that sick days are associated with a loss of productivity, this analysis suggests that SIT increases societal welfare. This conclusion also holds if there is no loss of productivity.

Does Specific Immunotherapy Injection Cause an Increase in Bronchial Reactivity?

Background. Several well-controlled studies have proven the clinical benefit of specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However, whether subcutaneous SIT injection could cause a transient increase in bronchial reactivity (BR) remains unknown. Objective. To investigate whether subcutaneous SIT injection, either during or outside the pollen season, could cause an increase in BR in children with pollen allergy. Methods. Twenty-two children (mean age 13.6 ± 0.7 years) with AR who were receiving maintenance SIT for 15 months were included in the study. Pre-injection BR of the patients was evaluated with methacholine provocation test immediately before maintenance dose of SIT during the peak pollen season and outside the season. The post-injection test was administered 24 hours after SIT injection. Results. There was no difference in FEV1 measures recorded during [98(93–109)%] and outside [102(96–111)%] the pollen season. There was no significant difference between pre- [64(7–64)mg/mL] and post-allergen injection [32(7.5–64) mg/mL] BR outside the pollen season (p = 0.9). A trend towards improvement following allergen injection [64(5.4–64)] as compared to pre-allergen injection [14.6(3.5–64)] was shown during the pollen season (p = 0.053). Although PC20 measures in the pollen season were lower than outside the season, the difference was not significant. The percentage of the patients with bronchial hyperreactivity was 62% during and 43% outside the season. Conclusion. SIT injections both during and outside the pollen season cause no increase in BR in children with AR. This calls into question the necessity of empirical dose reduction during the pollen season.

Cluster-Immuntherapie bei allergischer Rhinokonjunktivitis und Asthma bronchiale: Sicherheit der Initialtherapie mit Novo-Helisen Depot

Background: Specific immunotherapy (SIT) represents the only causal treatment that can be offered to allergic patients apart from allergen avoidance. In classic SIT, gradually increasing dosages of the allergen extract are injected subcutaneously. Several dosage schedules for subcutaneous SIT can be applied. The classic approach involves single injections at each therapy visit. In Cluster-SIT, two to three injections per day of treatment are given once a week during initial treatment. Patients: In this trial, we investigated 46 patients (17 female, 29 male) from 11 - 71 years (40.7 ′ 13 years) with regard to side effects of a Cluster regime during induction treatment with Novo-Helisen Depot. Four patients were treated with two different extracts, so that a total of 50 initial therapies were observed; 19 patients (41%) suffered from bronchial asthma. Results: We performed 34 treatments with mite extracts, eight treatments with grass pollen extracts and eight treatments with tree pollen extracts with 744 injections in total. The total number of enlarged local reactions (≥ grade 1) was 23, or 3.1% of all injections. Of these, 22 (3.0%) were classified as immediate reactions and one (0.1%) was a late-phase reaction. Of all enlarged local reactions, 22 (3.0%) were grade 1 reactions (5 - 8 cm) and one (0.1%) was a grade 2 reaction (8 - 12 cm). Grades 3 and 4 reactions were not observed. Only one systemic reaction was observed (0.1% of all injections). This reaction was a delayed phase reaction grade 1 (urticaria). Grades 2, 3, or 4 reactions did not occur. There were no differences in gender or age regarding the occurence of side effects (all p > 0.05). Conclusions: Frequency and severity of adverse side effects in Cluster-SIT with Novo-Helisen Depot show an excellent tolerability corresponding to the occurrence of side-effects with other dosage schedules.

Comparison of immunological changes induced by sublingual and subcutaneous specific immunotherapy in children with allergic respiratory disease

Rationale Sublingual immunotherapy (SLI) is effective for treating patients with respiratory allergies but the underlying immunological mechanisms remain unknown. We evaluated the immunological changes induced by subcutaneous immunotherapy (SCI) and SLI in children with allergic respiratory disease sensitized to Dermatophagoides pteronyssinus. Methods Group 1 (N=15) was treated with SCI and Group 2 (N=13) with SLI (ALK Abello) before (T0), one month (T1) and one year (T2) after starting immunotherapy. Total and specific IgE were determined by immunoassay and lymphocyte subsets, activation markers and intracellular cytokines by flow-cytometry. Results At T1 a significant increase in the CD4 subpopulation and monocytes, with a decrease in B lymphocytes was detected in Group 1. In both groups there was a significant increase in activated CD4, a decrease in activated CD8 cells, and a decrease in cytokine production (IFN-γ, TNF-α, IL-2, IL-4, IL-10 and IL-13), although only significant for IL-2 and TNF-α in the CD4 subpopulation. Although these changes were maintained at T2, there was also a significant decrease in IL-10, IL-13 and IL-4. No changes in total or specific IgE antibodies were found in either group. Conclusions Both types of immunotherapy induce very similar immunological changes, even immediately after administration. The relationship between these changes and the clinical symptoms needs to be established.

Safety of Subcutaneous Specific Immunotherapy with Pollen Allergen Extracts for Respiratory Allergy

Background: Specific immunotherapy (SIT) is a well-documented treatment for respiratory allergy. However, the major risk of SIT is the development of systemic anaphylactic reactions. Objectives: To evaluate the safety of SIT given by subcutaneous route for 3 years to patients with seasonal allergic rhinitis (AR) with or without asthma. Methods: A prospective open-label study of immunotherapy (Chenopodium album, Bermuda grass, or both) in 181 consecutive patients with AR with or without asthma. After an initial dose-escalation phase, a maintenance dose of 0.5 ml of 100,000 PNU/ml was administered monthly for 3 years. The occurrence and severity of systemic reaction (SR) and local reaction was recorded and graded according to the WHO position paper. Results: Of 181 patients enrolled, 57 (31%) did not complete the study (53 due to poor compliance and 4 due to systemic side effects). All 4 patients who developed SR had asthma and all the SR occurred during the dose- escalation phase. Three patients had moderate SR (grade 2), while 1 patient had severe reaction (grade 3). Three of the SR occurred within the first 20 min after injection and 1 SR occurred 2 h after injection. None of the reactions were life threatening and were managed easily. Total rhinitis symptom score decreased from 11.8 at baseline to 7.46 at the end of treatment (p < 0.001). The size of the skin prick test reaction to the main sensitising allergen was reduced from 7.48 ± 2.26 mm at baseline to 5.60 ± 2.18 mm at the end of treatment, p < 001. Conclusion: If a strict protocol is used, SIT is safe in AR patients with or without mild asthma and may result in significant subjective and objective improvement.

Analysis of the efficacy of specific immunotherapy with house-dust mite extracts in adults with allergic rhinitis and/or asthma

Allergen specific immunotherapy and allergen reduction are the only therapies in perennial allergic diseases to reduce symptoms in the long term. Specific immunotherapy has the potential to reduce symptoms and the need for medication significantly and furthermore to prevent progression into more severe disease e. g. asthma. The clinical value of specific immunotherapy has been studied for the last 30 years. We undertook an analysis of clinical trials of subcutaneous specific immunotherapy with Der p or Der f in adults to assess the efficacy of this controversial form of allergy treatment. A computerized bibliographic search revealed 13 randomised double-blind, placebo-controlled trials of specific immunotherapy with Der p/Der f for rhinitis and/or asthma in adults since 1970. The results extracted included patients symptoms, medication requirements, lung function, specific challenge-tests as titrated nasal, conjunctival or bronchial challenge test and side effects. For studies with continuous outcomes as symptom score and medication score the effect size was obtained by the difference in the scores between the active therapy and the placebo groups. For studies with categorical outcomes as increase or decrease in challenge-tests the results were expressed as odds ratios for improvement against no change and 95 % confidence intervals were calculated. Focused on the studies after 1980 there was a significant improvement on symptom score and medication score in the actively treated group compared to the placebo group, while the lung function was not significantly altered. Allergen provocation tests reflect the sensitivity of the shock organ. As the documentation of the clinical effects measured by challenge tests shows a highly significant improvement in the actively treated group, we recommend allergen provocation tests as a useful and sensitive parameter during specific immunotherapy. The risk of life-threatening side effects is low, although severe anaphylactic reactions may be induced. Specific immunotherapy using a standardized house-dust mite extract is effective and safe in adults when administered under optimal conditions.

Treating the allergic patient: think globally, treat globally.

Treating the allergic patient: think globally, treat globally.