Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis.
Topic: Immunotherapy

To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT.

PICO
Population: Patients with allergic asthma
Intervention: Allergen Immunotherapy (AIT)
Comparison: Standard care or placebo
Outcomes: Effectiveness, cost-effectiveness, and safety of AIT

Included studies:
title: [Neurocristopathy in pediatric neurosurgery].
title: Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. I. Clinical effect evaluated by diary cards and a retrospective assessment.
abstract: Forty-six asthmatics with verified allergy to the house dust mite, D. pteronyssinus (Dp), participated in a double-blind study comparing the effect of 2 years' hyposensitization with two different Dp extracts. Two groups received either monomethoxypolyethylene glycol modified (mPEG) Dp extract or the corresponding non-modified extract, and a third group acted as controls receiving no injections. Medicine consumption, symptom scores, and peak expiratory flow (PEF) were recorded daily from September to December prior to and after 6 and 18 months of treatment. Changes were calculated choosing changes greater than or equal to 10% as relevant. In addition, patients were asked to give their direct assessment of the clinical effect at the end of the study. After 6 months, there was an improvement in symptoms + medication in 11/14 of Dp-treated, 6/17 of the mPEG-Dp group (P greater than 0.05) and 3/15 of openly treated controls. Few patients had changed in PEF. During the second year, several Dp-treated relapsed and some controls improved. At the end of the study the same improvement rate was seen in all groups. Similarly, the retrospective questionnaire data did not disclose any significant differences between groups after 2 years. In conclusion, hyposensitization with unmodified Dp extract seemed to have a favourable short-term effect on bronchial symptoms + medication in the majority of patients. When mainly on maintenance dose, the beneficial effect was reduced. The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses. Changes in medicine and symptom scores only partly correlated to retrospective assessment, thus stressing the problems in this kind of evaluation.
title: Hyposensitization with Dermatophagoides pteronyssinus antigen: trial in asthma induced by house dust.
abstract: A double-blind clinical trial of hyposensitization with aqueous extracts of Dermatophagoides pteronyssinus (the house-dust mite) and human skin scales showed a substantial improvement in symptoms in 11 asthmatics allergic to house dust treated with the D. pteronyssinus extract and a reduction in their need for other therapy. Five patients were well for a year but six relapsed. These results contrasted with the generally unfavourable course of the patients treated with the extract of human skin scales. Asthma due to house-dust allergy may be substantially improved by hyposensitization with D. pteronyssinus extract.
title: Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial.
abstract: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma.
title: Development of cockroach immunotherapy by the Inner-City Asthma Consortium.
abstract: Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments.
title: A controlled trial of hyposensitization with adsorbed tyrosine Dermatophagoides pteronyssinus antigen in childhood asthma: in vivo aspects.
abstract: Continuing study for a second year and further analysis of a double-blind placebo controlled trial, already briefly reported, of injections of tyrosine-adsorbed, glutaraldehyde-modified Dermatophagoides pteronyssinus antigen in fifty-one children with perennial asthma and positive bronchial challenge to the antigen, confirms that the patients receiving the treatment reduced their symptomatic medication more than controls, without deterioration of symptoms. Some became symptom-free, when off all treatment. A double-blind placebo controlled trial of continuing treatment for a second year gave evidence of deterioration when the treatment was stopped. Within the treatment group, the improvement was associated with loss of late (6 hr) reaction to bronchial provocation with the antigen, but was not associated with change of immediate (20 min) reaction in lungs or skin. Those who improved in the placebo group did not lose their late reaction. There was a trend for similar benefit from active treatment in the control group, during the second year, though less than in the original active group, and only one lost his late reaction. Only one of the six children with very severe early onset asthma improved. Local reactions to either active or placebo (tyrosine) were seen in half the patients; these were mild and did not influence the treatment. Systemic symptoms occurred shortly after four active injections and after two placebo injections; only one patient stopped the treatment.
title: Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children.
abstract: The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents.
title: Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma.
abstract: Hyposensitisation with Dermatophagoides pteronyssinus tyrosine absorbate in asthmatic children with bronchial sensitivity to D. pteronyssinus was effective in a 12-month double-blind controlled clinical trial. Compared with controls, treated children used a smaller quantity of drugs while maintaining clinical and lung function improvements. In most children who improved there was no change in immediate response to D. pteronyssinus on bronchial provocation test, but the late reaction was lost in half the patients and these showed the greatest improvement in symptoms.
title: Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats.
abstract: Cells producing a T(H2)-cytokine profile play an important role in the onset and maintenance of atopic diseases, and therefore specific immunotherapy is aimed to induce a switch to cells producing a T(H1)- or T(H0)-cytokine profile. Recently, a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed, but its mechanisms of action are unknown.
title: A double-blind, placebo controlled study of Alpare mite D. pteronyssinus immunotherapy in asthmatic patients.
abstract: Results from one immunotherapy study can be difficult to extrapolate when physicians use products or dose schedules that differ from the ones used in that particular study. The purpose of this study was to determine if an alum absorbed Alpare D. pteronyssinus extract administered in a maintenance dose of 10,000-12,500 BU's could be shown to improve symptoms in asthmatic patients allergic to D. pteronyssinus. Previous studies using higher doses of extracts suggested efficacy but frequent side effects were noted. A double blind placebo controlled study was performed which included 24 active and 25 placebo patients. We measured skin reactivity, methacholine challenge changes, symptoms by visual analog score, specific IgE levels, and end of study assessment. The results showed significantly greater improvement in actively treated patients versus those given placebo in specific IgE levels, symptoms by visual analog score, and end of study status. We saw no significant differences in skin reactivity, methacholine challenge, or diary medication scores. In addition, no difference in side effects was noted between the two groups. We conclude that the dose administered in this study was safe and well tolerated. Some clinical improvement did seem to occur but the study suggests that higher doses may be indicted in certain patients.
title: [Clinical evaluation for sublingual immunotherapy of allergic asthma and atopic rhinitis with Dermatophagoides Farinae Drops].
abstract: To evaluate the safety and efficacy of sublingual immunotherapy with 'Dermatophagoides Farinae Drops' in D. farinae allergic asthma and/or rhinitis patients.
title: Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.
abstract: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever.
title: Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy.
abstract: Inland areas of northern California have an intense grass pollination in the spring of each year. This is accompanied by a stirking rise in the incidence of asthma. We documented this relationship and designed a trial to test the efficacy of immunotherapy for grass-pollen asthma. Aeroallergen counts were performed on the roof of the allergy clinic of David Grant Medical Center from January 1981 to December 1984 by a gravity collector. These counts were compared to counts done on a Rotorod at a nearby hospital from July 1982 to September 1984. Climatologic factors were also tabulated. Visits for asthma and rhinitis to our emergency room and asthma admissions to our hospital were counted for the 4-year period. A randomized, double-blinded, placebo-controlled trial of immunotherapy with grass-pollen extract was performed from November 1984 to June 1985. Two groups of clinically and immunologically well-matched subjects were started on an accelerated preseasonal trial of immunotherapy. One group received a standardized grass extract, and the other group did not. Both groups received other extracts of aeroallergens to which they were skin test positive that occur locally in the spring and summer. This was done because of our dissatisfaction with a histamine placebo used in a previous pilot study. Symptom medication scores (SMS) and immunologic parameters were followed. For the 4-year period, grass-pollen count (GPC) correlated strongly with asthma emergency room visits (r = 0.90; p less than 0.001) and for rhinitis (r = 0.92; p less than 0.001). Asthma admissions also correlated strongly with GPC (r = 0.72; p less than 0.001). Other aeroallergens either did not correlate significantly or occurred in such small numbers that they could not be seriously considered. Rotorod counts supported these conclusions with the exceptions of some Basidiomycetes. Climatologic factors demonstrated no relationship to the incidence of asthma. Asthma SMS were lower in the grass-treated group, p less than 0.05. Rhinitis SMS were also lower but did not reach significance, p = 0.11. RGGI sIgE did not rise significantly in the grass-treated group but did in the placebo-treated group. RGGI sIgE rose in both groups, although to significantly higher levels in the grass-treated group, p less than 0.001. The asthma SMS were inversely related to increasing RGGI cumulative dose, p less than 0.10. Linear regression analysis of the dose-response scattergram suggests that a cumulative dose of approximately 90 micrograms of RGGI may be desirable.(ABSTRACT TRUNCATED AT 400 WORDS)
title: The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study.
abstract: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America.
title: Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.
abstract: The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint.
title: Hyposensitization in house dust allergy asthma. A double-blind controlled study with evaluation of the effect on bronchial sensitivity to house dust.
title: Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of bronchial responses to cat allergen and histamine.
abstract: Ten asymptomatic patients with normal pulmonary function were selected for a double-blind trial of immunotherapy in cat-induced asthma. Each patient had a positive prick test to cat pelt extract and also a positive bronchial challenge response to the same extract. Patients were randomly assigned to active treatment or placebo groups and received weekly or biweekly injections over a 3 to 4-month period. The 5 patients who received the active treatment received a cumulative dose of cat pelt extract that ranged from 16.4 to 44.8 mg of total solid containing 1.7 to 4.7 mg of cat allergen 1. Apparent systemic reactions were observed in 3 patients who received the placebo and 3 patients who received the active treatment. The 5 patients who received the active treatment showed a reduction in skin reactivity to cat pelt extract as well as a significant mean reduction in bronchial sensitivity to the same extract. The 5 patients who received the placebo showed no significant changes in skin reactivity or bronchial sensitivity to cat pelt extract. Bronchial response to histamine did not change significantly in either the active treatment of the placebo group.
title: SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms.
abstract: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma.
title: Cluster analysis and clinical asthma phenotypes.
abstract: Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model.
title: Genic heterozygosity in a population of Eutamias panamintinus.
title: Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial.
abstract: To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite.
title: Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite.
abstract: Although several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown.
title: Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study.
abstract: A double-blind, placebo-controlled study was carried out in 85 patients with a well-documented history of perennial asthma caused by house-dust mites. Patients received either placebo or sublingual immunotherapy (SLIT) with a standardized Dermatophagoides pteronyssinus (DP)-D. farinae (DF) 50/50 extract. After a run-in period, patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months. The cumulative dose was about 104000 IR, equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1. Symptom and medication scores and respiratory function were assessed throughout the trial. Serum specific IgE and IgG4 were determined before SLIT (t0) and after 6 (t1), 11 (t2), 17 (t3), and 25 months (t4) of SLIT. Mite exposure was evaluated at t0, t2, and t4 by semiquantitative guanine determinations. Patients aged 15 years and older were asked to assess their quality of life (QoL) by completing the SF20 (Short Form Health Status Survey) plus two items at t0, t2, and t4. Use of inhaled corticosteroids and beta2-agonists was significantly decreased after 25 months of treatment in both groups (P<0.03). SLIT patients showed significant improvements in respiratory function at t4 (% predicted FEV1 (P = 0.01), VC (P = 0.002), morning (P = 0.01) and evening (P = 0.03) PEFR), and reduction in daytime asthma score (P = 0.02). In the SLIT group, the post-treatment PD20 was 1.75 times higher than the baseline value. There was no change in PD20 in the placebo group. Compared to the placebo group, the SLIT group showed a significant increase in specific IgE DP(P = 0.05), IgE DF(P = 0.02), IgG4 DP(P = 0.001), and IgG4 DF (P = 0.001) levels after SLIT. QoL scores were similar in both groups at t0 and t2. At t4, all scores were better in the SLIT group than in the placebo group, with the differences being most marked for the general perception of health (P = 0.01) and physical pain (P = 0.02). Adverse events were similar in the two groups. This study shows that SLIT in house-dust-mite-related asthma has a good safety profile and improves respiratory function, bronchial hyperreactivity, and QoL.
title: Diagnosis and immunotherapy of mould allergy. V. Clinical efficacy and side effects of immunotherapy with Cladosporium herbarum.
abstract: A placebo-controlled, double-blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics. The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season. An aqueous preparation of a potent, biologically standardized and purified extract was used in a clustered dose-increase regimen. The clinical efficacy was evaluated by a combination of symptoms (asthma score + peak flow) and consumption of antiasthmatic medication. The mean changes in symptoms and medication consumption over a 10-week registration period (peak Cladosporium season) in 1982 after 5-7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10-week period. A significant (P = 0.03) difference in terms of "improved", "unchanged" and "deteriorated" patients in favour of Cladosporium treatment was found. Approximately 80% in the Cladosporium group showed improved/unchanged symptoms contrary to 30% of the placebo treated. Side effects were observed frequently but only in the Cladosporium-treated. About 70% experienced a large local reaction and 100% had episodes of asthma during dose-increase phase. Only a few severe systemic reactions occurred. Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics.
title: Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. I. In vivo and in vitro parameters after a short course of treatment.
abstract: Dermatophagoides pteronyssinus (Dp) is the major allergen in allergic asthma in France. Standardized and lyophilized Dp extracts are available, and their effectiveness after a short course of rush immunotherapy was examined in a placebo-controlled, double-blind study. Twenty patients received the Dp standardized extract, and 10 other patients received a placebo extract. Before and 7 weeks after rush immunotherapy, in vivo and in vitro parameters were examined. Bronchial provocation tests performed in a standardized manner demonstrated that a provocative dose causing a 20% fall in FEV1, a 25% fall in maximum mild expiratory flow rate, a 25% fall in maximum flow when 50% of the forced vital capacity has been expired, and a 35% fall in specific airway conductance were significantly (p less than 0.005 to p less than 0.01, Wilcoxon W test) improved in the treated group and remained unchanged in the placebo group. Skin test titration demonstrated that patients placed in the treated group had a significant (p less than 0.001, Wilcoxon W test) decrease of both end point titer and size of the largest wheal. No significant difference was observed in the placebo group. Serum Dp-IgE did not vary significantly in either group. Serum Dp antigen P1-IgG was significantly (p less than 0.001, Wilcoxon W test) increased in the treated group and slightly increased in the placebo-treated group. This study demonstrated that a Dp standardized extract administered by a rush protocol elicits a rapid and significant immune response and leads to a significant protection of the patients.
title: Phoenix sylvestris Roxb pollen allergy: a 2-year randomized controlled trial and follow-up study of immunotherapy in patients with seasonal allergy in an agricultural area of West Bengal, India.
abstract: Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy, there is no report of a double-blind placebo-controlled trial with standardized pollen extract in seasonal respiratory allergy from India. In the agricultural area of eastern India, Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season.
title: House dust mite sublingual immunotherapy is safe in patients with mild-to-moderate, persistent asthma: a clinical trial.
abstract: The safety of allergen immunotherapy (AIT) in asthma has not always been sufficiently documented; accordingly, fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context. In a double-blind, placebo-controlled, randomized clinical trial, house dust mite (HDM) sublingual AIT was found to be efficacious in moderate, persistent asthma. The trial's safety results are now reported in detail.
title: Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: a multi-center, double-blind, randomized, and placebo-controlled study in Taiwan.
abstract: Sublingual immunotherapy (SLIT) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies, though more data is needed from well-controlled studies for documenting its efficacy in different ethnic populations. Ninety-seven children (age range 6-12 years), mild-to-moderate asthma with a single sensitization to mite allergen, were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with standardized mite extracts, which contain Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.). Patients were double blinded and randomly assigned to either a SLIT or placebo group. Following 24 weeks of study period, symptom and medication scores, lung function tests, skin prick tests, total serum IgE, and specific IgE to D.p. and D.f. were recorded. The results showed that there was statistically significant difference between these two groups in the analysis of daily (P=0.011), nighttime (P=0.028), and daytime (P=0.009) asthmatic scores after 24 weeks of treatment. Patients receiving SLIT improved their forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory flow (PEF) as compared to baseline (P=0.042, P=0.048, and P=0.001, respectively). No differences were found in skin prick test, total serum IgE and specific IgE to D.p. and D.f. Tolerance with high-dose SLIT was good with few minor adverse events reported. Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan.
title: Liposome-entrapped D. pteronyssinus vaccination in mild asthma patients: effect of 1-year double-blind, placebo-controlled trial on inflammation, bronchial hyperresponsiveness and immediate and late bronchial responses to the allergen.
abstract: Allergen vaccination is effective in mite-allergic asthma. Liposomes are immunological adjuvants that can act as allergen carriers.
title: Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate.
abstract: Immunotherapy is a recognized treatment for allergic respiratory diseases.
title: Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study.
abstract: Mite sensitivity is highly prevalent in tropical and subtropical regions, such as the Canary Islands.
title: [Safety and efficacy of specific sublingual immunotherapy in patients with asthma and allergy to Dermatophagoides pteronyssinus].
abstract: First reports on sublingual immunotherapy were published in 1980.
title: Immunotherapy in allergy to dog. Immunologic and clinical findings of a double-blind study.
abstract: Twenty-seven dog-allergic asthmatic children with no pets in the home were included in the study. The clinical trial was performed as a double-blind study using a commercial standardized aluminum hydroxide-bound dog dander and hair extract or histamine-placebo. The patients were randomized into the active treatment or the placebo group on the basis of the RAST (e5) and the provocation test with aqueous dog dander and hair extract. The good clinical response of immunotherapy with dog dander and hair extract has been reported earlier. The specific immunotherapy resulted in an increase in the serum level of antigen-specific IgG antibodies (P less than .01) and a decrease in the skin sensitivity to dog extract (P less than .001) in the active treatment group when compared with the placebo group. The treatment was well-tolerated. No systemic reactions occurred and local reactions were mild. The results show a good immunologic response with a standardized dog dander and hair extract. There were no major changes in the course of bronchial asthma in either group. After 1 year of immunotherapy the subjects had no symptoms on a dog-exposure of short duration. This must be carefully emphasized when considering the indications for immunotherapy.
title: A double-blind trial of oral immunotherapy for Artemisia pollen asthma with evaluation of bronchial response to the pollen allergen and serum-specific IgE antibody.
abstract: Eighteen asymptomatic Artemisia pollen asthma patients with normal pulmonary function were selected for a double-blind trial of oral immunotherapy. Each patient had a positive skin test to Artemisia pollen extract and also a positive bronchial challenge response to the same extract. The patients were randomly assigned to active treatment or placebo group and received intensive oral administration of Artemisia pollen extract over a 50-day course. The nine patients who received the active treatment ingested a cumulative dose of 396,652 PNU and showed a significant decrease in serum-specific IgE antibodies (P less than .05) and a significant reduction in bronchial sensitivity to the same extract (P less than .01). The changes in these two variables correlated well (r = .8787, P less than .01). The nine patients who received the placebo showed no significant changes in serum-specific IgE or bronchial sensitivity to Artemisia pollen extract. Follow-up of two cases with the same extract showed that the reductions in serum-specific IgE as well as bronchial sensitivity induced by oral immunotherapy were maintained for 3 months.
title: Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study.
abstract: To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys, mean +/- SD age of 11.7 +/- 3.3) allergic to house dust mite (HDM) into a double-blind, placebo-controlled study. After a run-in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests. Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow-up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group (P = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (P = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side effects from SLIT. Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM.
title: Immunotherapy in allergy to dog: a double-blind clinical study.
abstract: Twenty-seven asthmatic children allergic to dog were included in the study. Their allergy to dog was confirmed by positive results from the skin prick, radioallergosorbent and provocation tests. The subjects were randomly assigned to active and placebo groups. Fifteen subjects received immunotherapy with a commercial standardized aluminum hydroxide-bound dog dander extract and 12 subjects received placebo injections containing histamine. After one year's therapy the conjunctival sensitivity to dog dander extract had decreased significantly (p less than 0.001) in the active treatment group compared to the placebo group. The hyposensitization effect was already observable after six to eight months of treatment. The decrease in bronchial sensitivity was less marked than that in conjunctival sensitivity and statistically not significant. Immunotherapy was observed to be safe and effective. No systemic adverse reactions occurred and local reactions were mild.
title: A double-blind, multicenter immunotherapy trial in children, using a purified and standardized Cladosporium herbarum preparation. I. Clinical results.
abstract: A double-blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould-induced asthma and/or rhinoconjunctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum. Immunotherapy was given for 10 months in a double-blind manner to randomized groups with either Pharmalgen/Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July-September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternata. However, medication scores were significantly lower in the treated group (P less than 0.01). Bronchial (P less than 0.01) and conjunctival sensitivity (P = 0.01) were significantly reduced in the Cladosporium-treated group but not in the placebo group after 10 months of treatment. This is the first double-blind clinical trial showing the clinical efficacy of immunotherapy in children with mould-induced asthma.
title: Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses.
abstract: The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity (p less than 0.05) and prick test titer (p less than 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular (p less than 0.05) and pulmonary (p less than 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 (p less than 0.001) and cat albumin (p less than 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.
title: Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma.
abstract: Few studies have investigated the use of specific immunotherapy (SIT) for childhood seasonal allergic asthma.
title: Results of a clinical trial with a Dermatophagoides pteronyssinus tyrosine adsorbed vaccine.
abstract: Twenty-eight patients were included in a double-blind placebo-controlled study of a vaccine containing tyrosine-adsorbed Dermatophagoides pteronyssinus antigen (Migen(R)). The aim of the trial was to show the efficacy and safety of Migen as a 6-injection course, with or without a follow-up course of 6 maintenance doses, for the treatment of bronchial asthma. The patients selected had suffered from perennial asthma for at least 2 years and gave a strong skin reaction to house dust mite. The subjects in the study were divided into two groups: one of twelve patients receiving only a standard course of six graded injections at weekly intervals and the other of sixteen patients receiving the same course followed by a maintenance course comprising six injections of the highest strength (400 N.U.). Approximately half the patients in each of these groups were on placebo. Assessment was based on the patient's and doctor's impression of the response to the treatment using a daily symptom record card and clinical observation of the patient at regular intervals. The overall assessment was graded in accordance with the following four point scale: very good, good, same and worse. Results showed that the pa tients receiving Migen as a 6-injection course responded better than patients receiving placebo; moreover, patients who received 6 maintenance injections of Migen gave a very good or good response compared to those who were submitted to 12 injections of placebo and also compared to those receiving the standard course. Particular notice was taken of the side effects of the vaccine. Migen proved to be a good and and safe method of treating bronchial asthma due to house dust mite (D. pteronyssinus).
title: Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis.
abstract: Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)
title: Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial.
abstract: The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness.
title: House dust mite hyposensitization.
abstract: A double-blind controlled trial of house dust mite hyposensitization was carried out in 14 patients with asthma, who were hypersensitive on skin testing to the house dust mite alone. Measurements were made, using a Wright's peak flowmeter, during the 15-month trial period. Precautions were taken in the home to reduce the mite population. At the end of the trial, no clinical improvement was noted subjectively or objectively, despite a reduced bronchial sensitivity to allergen in the treated group. The role of the house dust mite as a cause of asthma is discussed.
title: Immunotherapy for cat asthma.
abstract: In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients were matched by the dose of the cat extract expressed in Food and Drug Administration (FDA) units of Fel d I (previously called cat allergen 1) required for end point reaction in intradermal skin test end point titration (STEPT), for in vitro leukocyte histamine release (LHR), and for the dose of cat extract producing a 20% fall in FEV1 (cat-extract PD20) in bronchoprovocation test. Patients were matched also for bronchoprovocation dose of methacholine producing a 20% fall in FEV1 (methacholine PD20). Patients were randomly assigned to one of two treatment groups. During immunotherapy, doses were increased to maintenance dose of 4.56 FDA units of Fel d I, or, if this were less, to the highest tolerated dose. Systemic reactions to cat-extract immunotherapy were mild and infrequent. Before and during immunotherapy, we measured (in FDA units of Fel d I) cat-extract PD20, cat-extract intradermal STEPT, cat-extract in vitro LHR, serum levels of cat IgG and cat IgE, and methacholine PD20. After they had received 1 year of immunotherapy, patients receiving cat extract, in comparison to patients receiving placebo, had decreased cat-extract PD20 (p less than 0.01), diminished responses to cat-extract intradermal STEPT (p less than 0.025), increased IgE antibodies toward cat extract (p less than 0.01), increased IgG antibodies toward cat extract, Fel d I, and cat albumin (p less than 0.001), but no significant change in cat-extract in vitro LHR or in methacholine PD20. We conclude that cat-extract immunotherapy was well tolerated, significantly decreased skin and bronchial responses to cat extract, and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract, Fel d I, and cat albumin.
title: A double blind controlled trial of house mite fortified house dust vaccine in childhood asthma.
title: Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers.
abstract: The prevalence of allergy to natural rubber latex proteins has increased over recent years among healthcare professionals but also in children undergoing multiple operations. Exposure to the antigen mainly occurs through the respiratory mucosa and the percutaneous route. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma, or anaphylactic shock. Preventive measures have been proposed to reduce the risk of sensitization by using only powder-free or synthetic gloves and latex-free material in operating units, but this is not always possible.
title: Clinical and immunologic evaluation of tyrosine-adsorbed Dermatophagoides pteronyssinus extract: a double-blind placebo-controlled trial.
abstract: We evaluated the clinical efficacy and immunologic changes associated with the administration of tyrosine-adsorbed Dermatophagoides pteronyssinus (Dpt) extract. The study was carried out in a double-blind, placebo-controlled fashion in 18 patients with Dpt-induced asthma during a trial period of at least 12 mo. Patients initially received six increasing doses once a week; the top dose of 400 Noon units was repeated at monthly intervals. Clinical response was on the basis of diary cards on which symptoms and medication scores were recorded; daily lung function measurements were made by use of a mini Wright's peak flow meter. The entire spectrum of physiologic measurements, medications, and symptoms were taken into account by computing daily scores over a 2-week period. Total IgE, Dpt-specific IgE antibodies, and leukocyte histamine release were measured before treatment and during hyposensitization. Changes in Dpt-specific IgG were evaluated with a double antibody antigen-binding assay by use of the purified fraction of mite extract F4P1. All patients had measurable levels of IgG antibodies to F4P1 before treatment. Treatment with tyrosine-adsorbed Dpt extract resulted in a significant increase of specific-IgG antibodies in the treated group at 2 and 6 mo only (nonparametric rank sum test). Variations relative to the pretreatment values of total and specific IgE were not significantly different in the treated and in the control patients after 2.6 and 12 mo. No significant decrease in leukocyte sensitivity was observed after treatment. It was only possible to demonstrate a significant diminution in the mean medication score (nonparametric sign test) in the first 6 mo for the treated group; independently of the beginning of the treatment, the treated group demonstrated a reduction of the mean medication score and an improvement in peak expiratory flow rate lung function before the midsummer months when seasonal increase in mite density can occur. Particular attention was paid to the methodological problems raised during this study and inherent in a trial in house dust-mite asthma.
title: Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.
abstract: For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.
title: Immunomodulation during sublingual therapy in allergic children.
abstract: The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated, but its mechanism of action is still controversial. The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, by co-stimulatory molecules, such as CD40 on B cells, and by hormones and neuropeptides. To better understand whether SLIT affects immune responses we used a double-blind placebo-controlled design. Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus (33 of whom also had rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP, IL-13, prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group, no variation in CD40 and ACTH, but a significant decrease in ECP, IL-13 and PRL after 6 months of therapy (p <0.01). Our results confirm the efficacy and safety of SLIT, and lead us to believe that it could modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL-13. In addition, the reduction of PRL might be a signal of reduced activation of T lymphocytes.
title: A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma.
abstract: Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed.
title: Hyposensitization with Dermatophagoides pteronyssinus in house dust allergy: a controlled study of clinical and immunological effects.
title: Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma.
abstract: Forty-one patients (21 adults and 20 children) with cat dander-or dog dander-induced asthma were selected for immunotherapy with standardized and partially purified cat- or dog-dander extracts by use of a double-blind protocol. Based on sex, age, clinical history, results of bronchial challenge, and crossed radioimmunoelectrophoresis studies, the patients were stratified in matched pairs, and the treatment alternatives were distributed randomly among the pairs. Twenty-two patients treated with allergen (15 with cat allergen and seven with dog allergen) and 17 patients receiving placebo therapy completed the first year of treatment. In the cat allergen-treated group, the bronchial sensitivity toward cat and histamine decreased (p less than 0.001 and p less than 0.05, respectively). Measured by bronchial challenge, the cat allergen-treated patients could tolerate 11 times more allergen at the end than at the start of the study, and they also demonstrated a tendency toward less pronounced symptoms after exposure to cat and dog allergens. No significant changes were observed in the dog allergen treated- or placebo-treated groups. The adverse effects in general were negligible except for some systemic side effects during rush hyposensitization, especially among the children, but these were mild and responded promptly to treatment.
title: Double-blind, placebo-controlled study of Alternaria alternata immunotherapy: clinical efficacy and safety.
abstract: Allergen-specific immunotherapy (ASIT) with fungal extracts has been beset by safety and efficacy problems, which result mainly from qualitative and quantitative variations. Little has been published on the safety and efficacy of these extracts. The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract. A total of 28 patients were selected with rhinitis and/or bronchial asthma because of Alternaria allergy and monosensitization to molds. The patients were randomized to an active ASIT or placebo group, both groups on a conventional immunotherapy schedule (increasing weekly doses until maintenance dose and then monthly doses). Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system. Clinical efficacy was analyzed for a year with symptom/medication diary cards, peak expiratory flow (PEF) measures, clinical severity score, severity of symptoms (visual analog scale), subjective evaluation of treatment by the patient and the physician, and a quality of life questionnaire. Twenty-three patients completed the study; all reached the established maintenance dose with only two mild adverse reactions in the whole sample. Significant improvements were found after 6 months in respiratory symptoms in the active treatment group, and in all symptoms in both groups. PEF increased significantly in the active treatment group but not in the placebo group. The severity of asthma decreased in the active treatment group, and the severity of rhinitis decreased in both groups. Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group, but only after 12 months in the placebo group. Physicians judged the disease course as significantly better in the active treatment group. ASIT with the A. alternata extract was safe, with clinical improvements after one year of treatment.
title: [Specific immunotherapy using Alpha-Fraction-Retard-D. pteronyssinus. Double-blind study in asthma].
abstract: A multicenter, double blind clinical study on two homogeneous, treated and untreated groups, has allowed an objective appreciation of the results of specific immunotherapy using the alpha-fraction of D. pteronyssinus in asthma. A statistically significant difference was seen of the consumption of drugs in the treated group and in infants of less than 5 years (p = 0.047). Tolerance, evaluated as a function of local and secondary effects was excellent and comparable in the two groups.
title: Effect of hyposensitization upon the immediate and late asthmatic reaction and upon histamine reactivity in patients allergic to house dust mite (Dermatophagoides pteronyssinus).
abstract: The effect of hyposensitization (HS) upon the allergen evoked immediate asthmatic reaction (IAR), late asthmatic reaction (LAR) and upon bronchial reactivity towards histamine was examined. Eighteen young asthmatic patients were studied using a double-blind, placebo-controlled design. All were allergic to house dust mite (HDM) and demonstrated an IAR and a LAR after bronchial provocation with HDM. Furthermore, all, except one child, demonstrated bronchial hyperreactivity towards histamine (median provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) histamine = 0.19 mg.ml-1, range: 0.02-8 mg.ml-1). The subjects were randomly divided into two groups to receive HDM or placebo injections during one year. After the one year period, the IAR was less severe in the subjects who received HDM injections (p = 0.02), while this reduction was not observed in the subjects who received placebo injections. Also, in the HDM group a small but significant increase of the median PD20 HDM was observed (p = 0.04). Furthermore, the LAR was less severe in the subjects who received HDM injections (p = 0.02), while the subjects who received placebo injections showed the same severity of LAR after one year (p = 0.44). Histamine reactivity did not change after HDM injections or after placebo injections. Thus, HS reduces the severity of the IAR and LAR without any change in histamine reactivity.
title: Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures.
abstract: Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.
title: Allergen vaccination with a liposome-encapsulated extract of Dermatophagoides pteronyssinus: a randomized, double-blind, placebo-controlled trial in asthmatic patients.
abstract: Liposomes are potent immunologic adjuvants and have been proposed as allergen carriers in allergy vaccination.
title: [Efficacy of specific sublingual immunotherapy with dermatophagoides farinae drops in the treatment of cough variant asthma in children].
abstract: To study the efficacy and safety of specific sublingual immunotherapy with dermatophagoides farinae drops in the treatment of cough variant asthma in children.
title: Economic evaluation of sublingual immunotherapy vs. symptomatic treatment in allergic asthma.
abstract: The worldwide increased prevalence of allergic diseases, and especially of respiratory allergy, is paralleled by increased health costs. This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice.
title: Double-blind and placebo-controlled study to assess efficacy and safety of a modified allergen extract of Dermatophagoides pteronyssinus in allergic asthma.
abstract: A randomized double-blind, placebo-controlled study was conducted in patients allergic asthma sensitized to Dermatophagoides pteronyssinus.
title: Immunotherapy with the storage mite lepidoglyphus destructor.
abstract: We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy.
title: A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults.
abstract: Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.
title: SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a randomised trial.
abstract: In a double-blind, placebo-controlled trial (EudraCT identifier: 2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated.
title: A controlled trial of immunotherapy for asthma in allergic children.
abstract: Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy.
title: A double-blind, randomized study investigating the efficacy and specificity of immunotherapy with Artemisia vulgaris or Phleum pratense/betula verrucosa.
abstract: This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris (Artemisia) extract. We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinically important allergies, either to Artemisia and Betula verrucosa (Betula) or to Artemisia and Phleum pratense (Phleum). Patient selection was randomized and evaluation of results was conducted in double blind fashion. Twenty patients completed two years of specific immunotherapy. Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula (n = 3) or Phleum (n = 8). Treatment with Artemisia was followed by a significant decrease in skin sensitivity (p < 0.05) and eye sensitivity (p < 0.01) to Artemisia but not to Betula/phleum. No significant decrease was observed in medicine consumption or symptom scores. Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum (p < 0.001), and eye sensitivity to Betula or Phleum (p < 0.05), but not to Artemisia and had significant decreases in medicine and symptom scores (p < 0.05) in Betula/phleum seasons but not in the Artemisia season. The treatment was both effective and specific with the one unexplained exception that both patient groups (Artemisia and Betula/Phleum) decreased their skin sensitivity to Artemisia.
title: Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV. Occurrence and prediction of side effects.
abstract: A double-blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminium-hydroxide was added to the Dp-extract to give a depot effect (Dp-group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxypolyethylene glycol (mPEG-Dp-group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp-extract. In the Dp- and mPEG-Dp-groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp- and mPEG-Dp-groups had systemic reactions (P greater than 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG-Dp-group: 5.1% compared to 9.0% in the Dp-group (P less than 0.01). In the mPEG-Dp-group, reactions were mild to moderate, mainly late-occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp-group. The reduction in side effects seems promising, but a further dose increase in the mPEG-Dp-group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test-sensitive to Dp prior to treatment. All patients skin test-positive to less than or equal to 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.
title: Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study.
abstract: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite-induced respiratory allergy.
title: Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid.
abstract: Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.
title: Safety of ultra-rush titration of sublingual immunotherapy in asthmatic children with tree-pollen allergy.
abstract: The recommendation to use sublingual-swallow immunotherapy (SLIT) in children and adults with allergic rhinitis has been established over the past decade. Recently, ultra-rush titration of SLIT has become more and more common, raising concerns about its safety in children with asthma. Fifty-four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen (birch and possibly alder and/or hazel) from 14 study centers in Germany participated in a randomized, double-blind, and placebo-controlled study. Twenty-seven were randomized to receive SLIT with standardized birch pollen allergen extract and the other 27 to receive placebo. An ultra-rush high-dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity (IR) within 90 min (30–90–150–300 IR) was used. The difference in mean PFR changes during ultra-rush titration between SLIT and placebo was not significant (p = 0.056). A 95% probability that SLIT does not decrease PFR during ultra-rush titration was demonstrated. Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred. No serious adverse event assessed by the investigator as related to study drug treatment was reported.
title: A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy.
abstract: Thirty patients with asthma and/or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected. Two groups were established at random: an active group and a placebo group, and a double-blind study was done on treatment with immunotherapy for a period of 3 continuous years, with initiation doses administered according to the rush immunotherapy technique. Grass-pollen allergen extract Alutard SQ and histamine as a placebo were used. The objective parameters of efficacy evaluated were end-point cutaneous tests, conjunctival provocation, bronchial provocation, and symptom/medication scores, as well as specific immunoglobulin determinations. The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group, and there were significant differences between the two groups for all of the parameters considered. We found no relationship between clinical improvement and the range of specific immunoglobulin E values. Regarding the safety of the treatment, systemic adverse effects were manifested only in the initial phase (rush immunotherapy), and were easily controlled by treatment. We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients.
title: Immunotherapy in patients allergic to cat and dog dander. I. Clinical results.
abstract: Twenty-four asthmatics allergic to cat and/or dog dander were included in a study to examine the efficacy and safety of immunotherapy (IT) with partially purified, standardized extracts of cat or dog dander. In the first placebo controlled, double-blind part of the study, 10 patients were treated with extracts of both cat and dog, 12 with cat extracts and 2 with dog extracts. Fifteen patients received active IT and 9 placebo injections. Patients treated with both extracts received active extracts only, or placebo only. Bronchial allergen challenge after 5 months demonstrated a significant fall in sensitivity to cat (P = 0.04) in patients treated with cat extracts. No significant changes were found in sensitivity to dog after treatment with dog dander extract or in the placebo groups. During this period, bronchial sensitivity to histamine did not change significantly in any of the groups. To examine the effect of more prolonged IT, 19 patients allergic to cat (17) and/or dog (9) were treated for 12 months. Bronchial sensitivity to cat decreased further (P = 0.003), while no significant change was found in dog extract-treated patients. In cat extract-treated patients a significant decrease in bronchial histamine sensitivity developed (P = 0.02). Systemic side effects were few, but in some cases, local side effects were a dose-limiting factor. This study demonstrated that IT with cat extract may benefit cat-allergic asthmatics, whereas no influence of IT with dog extract was detected in dog-sensitive asthmatics.
title: [Efficacy of sublingual immunotherapy in children with dust mite allergic asthma].
abstract: To compare the efficacy of sublingual immunotherapy (SLIT) combined with inhaled corticosteroids (ICS) versus ICS alone in children with mild and moderate dust mite allergic asthma.
title: Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study.
abstract: Few placebo-controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo-controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients.
title: Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial.
abstract: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen.
title: The effect of preseasonal immunotherapy on the production of histamine-releasing factor (HRF) by mononuclear cells from patients with seasonal asthma: results of a double-blind, placebo-controlled, randomized study.
abstract: The effect of immunotherapy on the production of histamine-releasing factor (HRF) by mononuclear cells (MNC) from patients with seasonal asthma was investigated in a double-blind, placebo-controlled, randomized study. Twenty-four patients with asthma were randomly divided into a placebo-treated group and a grass pollen-treated group. In vitro production of HRF by MNCs and the provocative concentration of histamine that causes 20% fall in FEV1 were measured before and after immunotherapy, and symptoms were monitored during the pollen season. MNCs from the patients were either cultured alone, spontaneous HRF production (spHRF), or in the presence of grass allergens (grass-stimulated HRF production), and the supernatants were assayed for HRF activity with basophils from a single donor after the study. We found that MNCs from patients with seasonal asthma to grass pollen spontaneously produce substantial amounts of HRF. The group of patients treated with placebo developed typical symptoms in the pollen season and also an increase in HRF production. In contrast, patients treated with grass pollen demonstrated reduced symptoms and no increase in spHRF production. A high degree of correlation between spHRF productions and symptom scores in both treated groups was noted. After 2 years of immunotherapy, allergen-stimulated HRF production decreased significantly, whereas spHRF production decreased significantly only in the patients who were clinically benefitted. The change in the provocative concentration of histamine that causes 20% fall in FEV1 during the pollen season highly correlated with the change in HRF production. The results of this study suggest that HRF might be involved in the pathogenesis of atopic asthma.
title: Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study.
abstract: Twenty-eight patients (14 in an active treatment group and 14 in a placebo group) with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a placebo-controlled, randomized, double-blind study to evaluate the risk-benefit quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I antigen. The cat extract was biologically standardized and quantified with monoclonal antibodies (100 biological units: 33 microgram of Fel d I antigen, 650 micrograms of albumin, and 99 micrograms of Fel d Bd/K30 antigen). After 1 year of treatment, the systemic reactions to cat extract immunotherapy were mild and infrequent. Improvement was observed in the active treatment group in comparison with the placebo group in the medication-symptoms score (p < 0.001); in skin prick test (p < 0.001), conjunctival provocation test (p < 0.001), and allergen bronchoprovocation test (p < 0.05) results, and in nonspecific bronchial hyperreactivity measured with methacholine, which was not statistically significant. This study demonstrates the favorable risk-benefit quotient of the dose of 13.2 micrograms of Fel d I antigen, which may serve as a future reference in defining the optimum dose and appropriate proportion of antigens that should be administered in cat extract immunotherapy.
title: House dust mite sublingual immunotherapy is safe and appears to be effective in moderate, persistent asthma.
abstract: The efficacy and safety of sublingual immunotherapy in house dust mite-induced asthma have yet to be firmly established. We report the results of a double-blind, placebo-controlled, randomized clinical trial performed in mainland China.