Rush immunotherapy with a standardized Bermuda grass pollen extract. Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. Early effects of rush immunotherapy with Dermatophagoides pteronyssinus in asthmatics. A controlled trial of immunotherapy for asthma in allergic children. Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients. Decrease of skin and bronchial sensitization following short-intensive scheduled immunotherapy in mite-allergic asthma. A double-blind, placebo controlled study of Alpare mite D. pteronyssinus immunotherapy in asthmatic patients. Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study. Effect of immunotherapy in bronchial asthma: treatment with extracts of house dust and mite. A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. III. Efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma. Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite. Diagnosis and immunotherapy of mould allergy. V. Clinical efficacy and side effects of immunotherapy with Cladosporium herbarum. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy. Ragweed immunotherapy in adult asthma. Activation of B-lymphocytes during pollen season. Effect of immunotherapy. Comparison between rush immunotherapy with a standardized allergen and an alum adjuved pyridine extracted material in grass pollen allergy. Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses. Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes. Complexes of grass pollen allergens and specific antibodies reduce allergic symptoms and inhibit the seasonal increase of IgE antibody. Allergen vaccination with a liposome-encapsulated extract of Dermatophagoides pteronyssinus: a randomized, double-blind, placebo-controlled trial in asthmatic patients. Immunotherapy in patients allergic to cat and dog dander. I. Clinical results. Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study. Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. A double blind controlled trial of Bencard house dust mite (Migen) hyposensitisation in Zambian asthmatics. Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV. Occurrence and prediction of side effects. [Double blind desensitization in asthma]. Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis. Clinical and immunologic evaluation of tyrosine-adsorbed Dermatophagoides pteronyssinus extract: a double-blind placebo-controlled trial. A controlled trial of hyposensitization with adsorbed tyrosine Dermatophagoides pteronyssinus antigen in childhood asthma: in vivo aspects. Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study. Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity. Hyposensitization in house dust allergy asthma. A double-blind controlled study with evaluation of the effect on bronchial sensitivity to house dust. Effect of hyposensitization upon the immediate and late asthmatic reaction and upon histamine reactivity in patients allergic to house dust mite (Dermatophagoides pteronyssinus). The value of hyposensitization therapy for bronchial asthma in children--a 14-year study. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study. A double blind controlled trial of house mite fortified house dust vaccine in childhood asthma. Specific immunotherapy with a standardized latex extract in allergic workers: a double-blind, placebo-controlled study. Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of bronchial responses to cat allergen and histamine. Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma. 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. Effect of allergen specific immunotherapy (IT) on natural killer cell activity (NK), IgE, IFN-gamma levels and clinical response in patients with allergic rhinitis and asthma. Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy. Immunotherapy vs inhaled budesonide in bronchial asthma: an open, parallel, comparative trial. Short-term immunotherapy: a prospective, randomized, double-blind, placebo-controlled multicenter study of molecular standardized grass and rye allergens in patients with grass pollen-induced allergic rhinitis. Immunotherapy with an extract of Olea europaea quantified in mass units. Evaluation of the safety and efficacy after one year of treatment. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma--a placebo controlled study. Significant reduction of nonspecific bronchial reactivity in patients with Dermatophagoides pteronyssinus-sensitive allergic asthma under therapy with allergen-antibody complexes. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. Allergen-antibody complexes can efficiently prevent seasonal rhinitis and asthma in grass pollen hypersensitive patients. Allergen-antibody complex immunotherapy. Immunotherapy with a depigmented, polymerized vaccine of Olea europaea pollen allergens. Significantly reduces specific bronchial and skin test reactivity in sensitized patients after one year of treatment. Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study. Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial. Hyposensitisation in mite asthma. Immunotherapy for cat asthma. Effects of immunotherapy on symptoms, PEFR, spirometry, and airway responsiveness in patients with allergic asthma to house-dust mites (D. pteronyssinus) on inhaled steroid therapy. A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults. Results of a clinical trial with a Dermatophagoides pteronyssinus tyrosine adsorbed vaccine. Dermatophagoides pteronyssinus cluster immunotherapy. A controlled trial of safety and clinical efficacy. Significant improvement in symptoms, skin test, and specific bronchial reactivity after 6 months of treatment with a depigmented, polymerized extract of Dermatophagoides pteronyssinus and D. farinae. Hyposensitization with Dermatophagoides pteronyssinus in house dust allergy: a controlled study of clinical and immunological effects. 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. The role of ragweed pollen in autumnal asthma. Immunotherapy in allergy to dog: a double-blind clinical study. [Specific immunotherapy using Alpha-Fraction-Retard-D. pteronyssinus. Double-blind study in asthma]. Effect of rush immunotherapy on airway inflammation and airway hyperresponsiveness after bronchoprovocation with allergen in asthma. Immunotherapy with the storage mite lepidoglyphus destructor. Comparison between the use of adsorbed and aqueous immunotherapy material in Dermatophagoides pteronyssinus sensitive asthmatic children. Failure of hyposensitisation in treatment of children with grass-pollen asthma. Immunotherapy with dog and cat extracts in children.
We carried out a double-blind clinical trial in 30 patients who were sensitized to Bermuda grass pollen. Before and after immunotherapy we performed in vivo tests (skin tests and standardized tests of specific and nonspecific bronchial hyperreactivity), in vitro tests (histamine release), and specific IgE and IgG antibodies to BGP. We found a significant decrease (P less than .001) in specific bronchial hyperreactivity and skin sensitivity to BGP in the group of patients treated with immunotherapy, a decrease in the delayed responses (P less than .05) in histamine release (P less than .01), and an increase (P less than .001) in specific IgE and IgG antibodies to BGP. The placebo group showed no changes in these parameters. 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.
                We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests (PD20FEV1) with a standardized Fel d 1 cat extract on Fel d 1-specific serum IgE and IgG levels and in vitro IL-4 and IFN-gamma production.
                Patients allergic to cats received 6 weekly injections of 7.5 micro(g) (low dose), 75 micro(g) (medium dose), or 750 micro(g) (high dose) of Fel d 1 peptides (25 patients) or a placebo (6 patients).
                Six weeks after ending immunotherapy, posttreatment PD20FEV1 was not significantly different between the treated and placebo groups. However, in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days. IL-4 release was significantly reduced in the high dose-treated group (P <.005, Wilcoxon W test), whereas it was unchanged in the low or medium dose- and in the placebo-treated groups. In all groups, IFN-gamma, IgE, and IgG levels remained unchanged.
                There was no correlation between the improvement of PD20FEV1 and the decrease in IL-4 production. These data suggest that peptide immunotherapy may act by shifting the Fel d 1-induced response of PBMCs in vitro from the T(H2)-like to the T(H0)-like phenotype. In this study we assessed the effects of Dermatophagoides pteronyssinus (Dpt) rush immunotherapy in comparison with placebo treatment in our asthmatic patients. Fourteen highly Dpt-susceptible adults were randomized in two groups (immunotherapy and placebo) and treated in single-blind manner. Patients were selected according to the recommendation of the immunotherapy position paper (1993). To minimize side effects we modified the protocol by adjusting allergen doses for each patient separately. Immunologic (total and Dpt-specific serum IgE and IgG antibodies/EIA, Pharmacia) and clinical parameters (spirometry, medication score and skin testing) were recorded before treatment, after 2 weeks, at the second month and after 4 months of immunotherapy onset. None of the patients had life-threatening side effects in the course of the treatment. The results obtained demonstrated significant influence of immunotherapy on Dpt-specific serum IgG synthesis (Kruskal Wallis test, p < 0.05) and on the late phase skin reaction with Dpt (U-test, p < 0.05) at the end of the second month of immunotherapy onset. In the immunotherapy group, we also registered a negative correlation between concentrations of Dpt-specific serum IgE and IgG antibodies (p = -0.83; p < 0.05), at the end of the second month. In addition, diversities among patients, expressed by immunologic parameters, were related to the amount of delivered allergen. There were no significant differences between groups concerning medication score from opposite to better FEV, PEFR and dPEFR results (Kruskal Wallis, p < 0.05) in the placebo group. In conclusion, Dpt-specific serum IgG concentration, immunologic score and late phase skin reactivity to allergen appeared to be the valid parameters of rush-immunotherapy achievement, while delivered allergen dose also seemed to be an influencing factor. Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy.
                We conducted a double-blind, placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma. The children, who required daily medication for their asthma, were randomly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo. Maintenance injections were continued for 18 months or longer. Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms. The principal outcome was the daily medication score. Bronchial sensitivity to methacholine (the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [PC20]) was measured twice yearly.
                The median medication score declined from 5.4 to 4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group (P<0.001), but there was no significant difference between the groups (P>0.6). The number of days on which oral corticosteroids were used was similar in the two groups. Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no difference between the groups in the use of medical care, symptoms, or peak flow rates. The median PC20 increased significantly in both groups, but again with no difference between the two groups.
                Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment. Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non-pharmacological challenges, has not been evaluated.
                Twenty-six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non-pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT.
                After 24 months, the SIT group showed a statistically significant reduction of the mean CACh-induced changes of both forced expiratory volume in one second (-21.8+/-2.7% vs. -13.7+/-2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (-48.9+/-4.9% vs. -27.9+/-6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs. 1/12; P<0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness.
                These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM-allergic paediatric asthma patients. Changes induced by high-dose intensive specific immunotherapy (ISI) were studied in 18 patients with mite-allergic bronchial asthma and compared with 18 control patients. A biologically standardized well-characterized Dermatophagoides pteronyssinus extract of known potency was used both for in vivo tests and ISI. Immediate D pteronyssinus skin tests (measured by parallel-line bioassay) were reduced 20-fold in ISI treated patients, and delayed skin responses significantly decreased and even disappeared following ISI. Bronchial tolerance to D pteronyssinus increased an average of ten times in ISI-treated patients, whereas nonspecific hyperreactivity remained unchanged. ISI induced significant specific IgG and IgG4 increases but no changes were observed in specific IgG1,2 and 3 or in specific IgE. Clinical score did not change significantly after ISI, short ISI schedule with a well-characterized mite extract greatly reduced the degree of mite sensitization (skin and bronchial allergic responses), but clinical disease failed to improve significantly, probably owing to the lack of influence of ISI in nonspecific hyperreactivity. 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. 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.
                Nineteen patients with a history of birch-pollen-induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment.
                All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty-four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group.
                Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti-inflammatory effect of the treatment. nan 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. Specific immunotherapy with unmodified formalinized allergoids is effective in grass-pollen allergy, but systemic reactions have been observed. A high-molecular-weight formalinized allergoid (HMW-GOID) was fractionated by gel filtration, retaining molecules of greater than 85,000 daltons in the expectation of improving safety without sacrificing efficacy. HMW-GOID and unfractionated allergoid (GOID) had a similar allergenic activity assessed by RAST inhibition, but the HMW-GOID preparation was 65 times less reactive when it was tested by skin prick test than the GOID preparation. A double-blind, placebo-controlled study was carried out in grass pollen-allergic patients with placebo (14 patients), GOID (15 patients), and HMW-GOID (13 patients). An additional group of 18 patients was treated by a rush schedule with a standardized orchard grass-pollen extract. A similar mean cumulative dose was administered with both allergoids. The fractionated allergoid only elicited minor systemic reactions similar to reactions elicited by placebo, whereas 20% of patients treated by GOID and 5.5% of patients receiving the standardized extract had a severe systemic reaction. For rhinitis, conjunctivitis, and asthma, the HMW-GOID and the standardized extract had a similar efficacy, significantly greater than placebo. GOID was less effective than the other two active treatments but was significantly more effective than placebo treatment for asthma and conjunctivitis. Although several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown.
                A double-blind, placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite (HDM; Dermatophagoides species) was conducted to assess the effects of specific immunotherapy added to guideline-adjusted pharmacologic treatment and allergen avoidance.
                After 1 observational year of pharmacologic treatment and standard measures of HDM avoidance, 2 groups of asthmatic subjects were randomly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine (n=41) or placebo (n=31) for 3 years. Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines.
                The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects. The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators, an increase in morning and evening peak expiratory flow, and a reduced skin sensitivity to HDM extracts. The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids, asthma symptoms, lung volumes, or bronchial responsiveness to methacholine.
                These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits, possibly by reducing the allergic response of asthmatic patients sensitized to HDM. 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. 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.
                The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma).
                We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated.
                Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients.
                Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma. 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) Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear.
                We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years.
                During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy.
                Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years. B-lymphocytes play an important part in the allergic reaction as producers of IgE antibodies.
                To investigate the cell surface expression of the activation antigens CD23, CD40 and HLA-DR on B-lymphocytes in birch pollen allergic patients before and during birch pollen season and to study the effect of immunotherapy.
                The study included 24 birch pollen allergic patients half of whom were treated with immunotherapy against birch pollen before the start of the season. Eleven of the 24 patients had asthma. Blood samples were taken and lung function was registered before the season began and before the immunotherapy treatment in January to February and during the season in May. The relative number of B-lymphocytes (CD19+) of the lymphocyte population and the cell surface expression of CD23, CD40 and HLA-DR on B-lymphocytes was measured by the use of flow cytometry.
                In the control group of patients the relative number and concentration of B-lymphocytes, the cell surface expression of CD23, CD40 and HLA-DR on B cells, and the serum concentration of IgE increased during season compared with before season. In contrast, in the immunotherapy treated patients no changes in the number of B cells or cell surface expression of CD23, CD40 and HLA-DR were demonstrated.
                The elevated expression of CD23, CD40 and HLA-DR on B cells, combined with increased levels of IgE in allergic patients during season could be explained by the effect of cytokines produced by activated TH2 cells. A shift from TH2 to TH1 cells might be the mechanism after the absence of signs of B-cell activation in immunotherapy treated patients. The prevention of increased cell surface expression on B cells by immunotherapy may constitute a significant mechanism behind the beneficial effects of immunotherapy in the treatment of pollen atopy. Rush immunotherapy with a standardized and lyophilized cocksfoot pollen extract was performed in twenty-three allergic subjects and compared with classical immunotherapy done with an alum adjuved, pyridine extracted cocksfoot pollen extract (fifteen subjects) and a control group of ten patients. The three groups were perfectly matched. Clinical benefits were analysed by means of symptom scores. It was shown that rush immunotherapy gave significantly better results when asthma or rhinitis was considered than either classical immunotherapy (P less than 0.02) or in the control group (P less than 0.01 and 0.02). Skin tests were significantly reduced after rush immunotherapy and did not change in the two other groups. After the pollen season the skin test reactivity was increased in the rush immunotherapy group. Cocksfoot pollen specific IgE did not vary significantly in the three groups. Cocksfoot pollen specific IgG was significantly (P less than 0.05) increased in the rush immunotherapy group before the pollen season and did not vary significantly in the other groups. 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. Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double-blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side-effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization. Complexes made from antigen and specific antibodies have been used to suppress specific antibody production. This property is of potential therapeutic interest in immediate hypersensitivity states which are characterized by hyperproduction of IgE antibodies. We report here on the use of antigen-antibody complexes in patients with hypersensitivity to grass pollen. Specific anti-allergen antibodies were prepared by immunoadsorption from the serum of hypersensitive individuals and mixed with grass pollen allergens to form complexes in antibody excess. These complexes were used in a strictly autologous manner for inoculating patients prior to and during a pollen season. The study comprised two randomly defined groups of 15 patients who were inoculated intradermally either with a preparation of allergen-antibody complexes or with the carrier buffer, according to a double-blind protocol. Diary cards were used to follow nasal and ocular symptoms, bronchial asthma and medication intake. Specific IgE antibodies were assayed during the trial and 1 year afterwards. Inoculation of allergen-autologous antibody complexes was well tolerated. It significantly reduced ocular symptoms (Mann-Whitney U-test, P less than 0.05), bronchial asthma during the first part of the season (Mann-Whitney U-test, P less than 0.001) and drug intake (Mann-Whitney U-test, P less than 0.001). This treatment prevented the seasonal increase in specific IgE antibodies, whose production continued to decrease after the pollen season. These effects were obtained within a few weeks of treatment, using a cumulative amount of allergen 100-fold lower than the amount which would have been used for a conventional hyposensitization.(ABSTRACT TRUNCATED AT 250 WORDS) Liposomes are potent immunologic adjuvants and have been proposed as allergen carriers in allergy vaccination.
                We sought to investigate the efficacy and safety of vaccination with Dermatophagoides pteronyssinus encapsulated in liposomes.
                We conducted a double-blind, placebo-controlled study. Fifty-five asthmatic patients sensitized to mites were randomly assigned vaccination with D pteronyssinus extract encapsulated in liposomes or empty liposomes for a period of 12 months. The principal parameters were symptom and medication-consumption scores. The percentage of healthy days (ie, days without medication and with absent or mild symptoms) was calculated. Immediate and late skin test results, allergen bronchial challenge test results, and allergen-specific serum immunoglobulin levels were evaluated before and after treatment.
                All clinical scores were markedly lower in the active group than in the placebo group after vaccination. Nearly half (45.8%) of the patients actively treated reduced their symptom and medication scores by at least 60% versus only 12% of patients receiving placebo treatment (P =.0388). The percentage of healthy days in the active group rose from 10.5% before treatment to 64.5% afterward (P =.0008). Reduction in organ sensitivity was demonstrated by skin prick test responses (P <.01), late-phase response after intradermal testing (P =.009), and bronchial challenge test results (P =.026) in the active group. Serum levels of specific IgG increased throughout the treatment, whereas specific IgE levels showed only an initial transient increase. No change in these parameters was observed in the placebo group. Vaccination was well tolerated, and no subcutaneous nodules appeared.
                Vaccination with D pteronyssinus encapsulated in liposomes is an effective and safe treatment for allergy-induced asthma. 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. To evaluate the effectiveness of specific immunotherapy (SIT) in patients with severe house dust mite (HDM)-induced perennial allergic rhinitis using diary cards and objective endpoints.
                Thirty-six adult patients were selected with moderate to severe allergic rhinitis due to HDM allergy uncontrolled by regular anti-allergic drugs. Twenty-eight patients completed the study, 22 of these patients also had mild asthma. Subjects were stratified for HDM sensitivity on the basis of their 4-week diary card score and the size of their immediate and late-phase skin reaction to HDM. The groups were well matched for all relevant parameters. Patients were randomized to receive active preparation (Alutard(R)-SQ, ALK, Dermatophagoides pteronyssinus extract) or an identical placebo preparation. Increasing doses were administered until the maintenance dose was reached. This dose was then given once a month for 12 months.
                Clinical efficacy was evaluated by symptom medication diary cards recorded for 4 weeks after 12 months of continuous treatment and compared with pre-treatment scores. Skin test reactivity was re-measured after 12 months of treatment to HDM, cat dander and codeine phosphate. After 1 year of treatment, the actively treated group showed a 58% reduction in diary card symptom scores (P<0.002) and a 20% reduction in the use of rescue medication. The placebo group had a 32% reduction in symptom scores (P=NS), but no reduction in rescue medication requirements. The active group showed 36% reduction in skin prick test sensitivity to D. pteronyssinus (P=0.006), while the placebo group values were unchanged. Skin reactivity to codeine was unchanged in both groups. No significant adverse reactions to SIT were encountered.
                One year of SIT for D. pteronyssinus in patients with poorly controlled rhinitis (+/-mild asthma) produced clinically useful improvement as shown by symptom-medication diary cards and reductions in immediate skin reactions compared with placebo treatment. Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements. Effects on seasonal asthma are less clear, and concerns over safety persist.
                The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms, bronchial hyperresponsiveness, and quality of life in seasonal rhinitis and asthma.
                Forty-four patients with severe summer hay fever (of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness) participated in a randomized, double-blind, placebo-controlled, parallel group study. After symptom monitoring for one summer, participants received injections of a depot grass pollen vaccine (n = 22) or matched placebo injections (n = 22) in a rapid updosing cluster regimen for 4 weeks, followed by monthly injections for 2 years. Outcome measures included hay fever symptoms and medication use, health-related quality of life, and measurements of nonspecific bronchial responsiveness.
                Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms (49%, 15%; P =.01), medication scores (80%, 18%; P =.007), and seasonal chest symptoms (90%, 11%; P <.05). Impairment of overall quality of life (mean score of 7 domains) during the pollen season was less in the immunotherapy group than in the placebo group (median difference [95% CI], 0.8 [0.18-1.5]; P =.02). During the pollen season there was no change in airway methacholine PC(20) (provocation concentration producing a 20% fall in FEV(1)) in the immunotherapy-treated group (P =.5), compared with an almost 3 doubling-dose decrease in the placebo-treated group (P =.01, between-group difference). There were no significant local or systemic side effects during the study.
                Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness. The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma. 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. 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.
                The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers.
                Seventeen patients with latex skin allergy and rhinitis (9 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (9 in the active group and 8 in the placebo group) for 1 year. Treatment started with a 2-day course of rush immunotherapy in hospital. Treatment efficacy was assessed after 6 and 12 months by means of symptom and medication scores recorded on diary cards. Conjunctival provocation tests were also performed.
                Patients in the active treatment group had a significantly lower total rhinitis score after 6 (P <. 04) and 12 months (P <.05), conjunctivitis score after 6 months (P <. 02), and cutaneous score after 12 months (P <.03) than in the placebo group. Asthma symptoms after 6 or 12 months of treatment were not significantly different between the two groups after adjustment for baseline values. The global medication score was markedly decreased in the latex-treated group. A significant difference in conjunctival reactivity was observed in favor of the active group: the number of patients for whom the threshold dose was increased after 12 months of treatment was significantly greater in the active group than in the placebo group (P <.02). Most injections were well tolerated, but several adverse effects, including hypotension, urticaria, wheezing, and pharyngeal edema, were observed.
                The clinical benefits observed during the present study included a significant improvement of rhinitis, conjunctivitis, and cutaneous symptoms. Immunotherapy also decreased allergen-specific conjunctival reactivity. Latex-specific immunotherapy may allow sensitized personnel to remain at work, but further trials need to be conducted in a larger number of patients. A double blind controlled trial of Bencard HDM (Migen) for the prophylaxis of asthma in a group of Zambian asthmatics failed to show any benefit. The trial results suggest that asthmatics can benefit from regular supervision and the position of prophylactic and therapeutic medication. 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. nan 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) 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. 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. The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America.
                We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia.
                Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial.
                Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002).
                Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia. To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity. nan 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. nan 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.
                Thirty-five patients with severe rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire.
                IT reduced the symptom score for both rhinoconjunctivitis and asthma (P-values < 0.05), total medication score (P < 0.02) and use of oral antihistamines (P < 0.01). IT reduced specific conjunctival sensitivity (P < 0.05), skin prick test, and especially cutaneous late-phase response diameters (P < 0.00001), and increased general well-being on post-seasonal evaluation (P < 0.01). IT was safe, with side-effects at the same level as placebo.
                High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen rhinoconjunctivitis and asthma. nan Preventive measures have been proposed to reduce the risk of sensitization to natural rubber latex (NRL), but this is not always feasible.
                The aim of this study was to determine the efficacy and safety of specific immunotherapy with a standardized latex extract in sensitized workers.
                Twenty-four patients allergic to NRL with contact urticaria (n = 8) and rhinitis or asthma (n = 16) were included (16 in the active group and 8 in the placebo group). Treatment started in a cluster immunotherapy protocol, with injections every week for 3 months and then every other week for another 3 months.
                Patients in the active group had significantly lower values than patients in the placebo group in skin terms of reactivity to NRL (P <.01), rubbing test results (P =.047), and latex glove use test results (P =.046) after 6 months of treatment. There were no significant differences between the active and placebo groups in symptom scores, use of medication, self-assessment, or methacholine test results either before or after treatment. Differences in nasal and bronchial symptoms during specific inhalation challenges (P = not significant and P =.05, respectively) were observed in favor of the active group. In the active group 32 systemic reactions were observed (8% of doses), mostly during the build-up period, being more frequent in patients with respiratory symptoms (P =.004). All reactions responded promptly to treatment.
                Clinical efficacy was shown mainly on cutaneous symptoms, although an improvement in rhinitis and asthma symptoms was also observed during specific inhalation challenges. Latex-specific immunotherapy might be a useful approach for the treatment of latex allergy in sensitized workers. 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. 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. 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. Allergen specific immunotherapy (IT) has been widely used for many years as a specific treatment of allergic diseases. A variety of changes in immunological parameters have been described but it still remains uncertain as to which of them is responsible for the improvement of symptoms. The aim of our study was to evaluate the effect of IT on natural killer (NK) cell activity, IL-4, IFN-gamma, IgE levels and skin test reactivity in addition to clinical efficacy. Thirty-one patients with allergic rhinitis and asthma were selected according to positive history, skin prick tests to Dermatophagoides pteronyssinus (Der p) or grass pollens, presence of specific IgE antibodies in sera and clinical findings, and were submitted to one year of placebo-controlled IT. Total IgE, specific IgE, IL-4 and IFN-gamma levels were measured by using ELISA method. Standard chromium 51 release assay was used to measure NK cell cytotoxic activity against the human leukemic cell line, K562 target cells. Mean symptom and medication scores, skin test reactivity and histamine sensitivity were significantly decreased in the patients given IT at the end of the first year when compared with the placebo group. However, there was neither a significant reduction in total and specific IgE levels nor a significant increase in IFN-gamma levels at the first year of IT. IL-4 levels were only measured at the beginning of the study because of the very low levels. A decrease in NK cell activity was found in patients treated with grass pollen extracts after 12 months when compared with Der p and placebo group. No signs of major local or systemic side effects due to IT were seen in patients during the study. Although significant clinical efficacy of specific IT with standardized extracts has been demonstrated in allergic rhinitis and asthmatic patients at the end of the first year of IT, no significant changes in immunological parameters were observed. However we conclude that a decrease in NK cell cytotoxic activity during IT has to be taken into account in the follow-up of patients. 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.
                Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy.
                Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol.
                PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups.
                Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance. Budesonide, an inhaled corticosteroid and specific immunotherapy, are both routinely used in the treatment of bronchial asthma. However, there are as yet, no studies comparing the effects of budesonide vs immunotherapy.
                The aim of this study is to compare the effects of budesonide with immunotherapy in patients having perennial asthma.
                This study is an open, parallel, comparative trial, in which 51 young patients were administered either immunotherapy or budesonide for 1 year and their global symptom scores and FEV1 values assessed. Both treatments were abruptly discontinued after 12 months and the effects of cessation analysed.
                The use of budesonide resulted in a faster and more striking improvement during the first few months as compared to immunotherapy, with an even more rapid decline in benefits on cessation of budesonide. Immunotherapy on the other hand, resulted in slow but steady improvement which did not decline as rapidly as budesonide on cessation.
                Although this was an open trial, it could be concluded that relief with inhaled corticosteroids in bronchial asthma is more rapid than immunotherapy; however the decline in benefit on cessation of inhaled corticosteroid is even more rapid, a phenomenon not seen with immunotherapy. Short-term immunotherapy (STI) can be beneficial for patients who are noncompliant with long-term specific immunotherapy.
                The efficacy and tolerance of STI with seven preseasonal injections of molecular standardized allergens from grass and rye pollen has been investigated in a double-blind, placebo-controlled multicenter study with 87 patients at 12 German University hospitals.
                Symptoms of the eyes, nose, and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and/or rye pollen and without bronchial asthma. Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4.
                The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower (p = 0.014) with 35.0 for STI (n = 41) versus 69.0 for placebo (n = 40); the overall symptom score was 54.0 for STI versus 97.5 for placebo (p = 0.020). Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo (p = 0.006); these patients also had fewer nasal symptoms and less use of topical nasal drugs (p < 0.001). The threshold dose in skin prick tests was significantly higher, being 9.06 histamine equivalent for skin prick test (HEP) for STI-treated patients who received the maximum dose (n = 22) versus 4.33 HEP for placebo (p = 0.005). Specific IgE levels were significantly higher, being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections (p = 0.006) and level of specific IgG4 was 5.36% for STI versus 1.28% for placebo (p < 0.001). No severe systemic reactions were observed.
                STI with seven preseasonal injections with molecular standardized allergens is effective and well tolerated. Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and bronchial asthma (BA) in the region of Jaén (southern Spain), where this allergen reaches atmospheric levels of almost 7000 grains/m3 during pollen season (May and June) and produces high morbidity. Specific immunotherapy (SIT) has proven very efficient in allergic RC and BA caused by grass pollen. Considering the availability of a biologically standardized extract of Olea europaea, with its major allergen quantified in mass units, we decided to investigate SIT with this extract in a group of rhinitic and/or asthmatic patients monosensitized to olive. We studied tolerance, safety, and efficacy by comparison of the active group (subjected to SIT) with a control group that did not receive SIT. A hyposensitizing dose of Olea europaea extract was administered preseasonally, establishing a maintenance dose 3.8 times higher than those administered in conventional treatments. Eighty-three percent of the patients reached the proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate of 0.8% of systemic reactions. A significant decrease in cutaneous (p < 0.001) and bronchial (p < 0.001) reactivity was observed in the active group, but not in the control group. Also, a decrease in specific IgE and an increase in IgG1 and IgG4 were found in the group of patients treated with SIT. Regarding clinical evolution, the active group, but not the control group, experienced a clear statistically significant improvement both in nasal (p < 0.05) and bronchial (p < 0.05) symptoms, in addition to a significant decrease in the consumption of antihistamines (p < 0.05) and beta 2-agonists (p < 0.01). In conclusion, SIT with olive extract proved to be safe and efficacious for the treatment of asthma and rhinitis caused by this allergen. The efficacy of therapy with sublingual allergen extracts is unproven.
                To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy.
                Thirty-six patients with rhinitis and asthma due to mite allergy were randomly divided into three groups in order to receive subcutaneous injections with allergenic extracts, sublingual drops with solutions of purified standardized allergen preparations, or sublingual placebo for a period of 1 year. Assessment of clinical and immunologic efficacy included symptom and medication scores, methacholine provocation tests, skin prick tests, and specific IgE and IgG4 antibody concentrations.
                Subcutaneous immunotherapy for both rhinitis and asthma was clinically effective. Patients treated with sublingual immunotherapy had decreased rhinitis symptoms (P < .01) but no change in asthma scores. Medication scores significantly decreased in both actively treated groups (P < .01) at the first year compared with baseline. When skin prick tests were evaluated, the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus (P < .01), D. farinae (P < .05), and histamine (P < .05) while other two groups showed no difference. There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline. No change in D. pteronyssinus and D. farinae specific IgE levels were observed; however, specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups (P < .05) after 1 year immunotherapy. No significant difference was obtained in any of these parameters in the placebo group.
                Sublingual immunotherapy may be effective in patients with allergic rhinitis. Further, we believe it is a potential therapy for allergic asthmatic patients. The clinical usefulness of this form of immunotherapy (when administered to larger study groups for a longer time) and the mechanisms underlying its immunologic effect deserve additional studies. Thirty-nine asthmatic patients hypersensitive to Dermatophagoides pteronyssinus were treated for a total of 4 yr with injections of complexes made of allergen and autologous specific antibodies. The results obtained throughout the first 2 yr of a double-blind placebo-controlled trial have been published (1) and we now report the results of such therapy during an additional 2 yr. Three groups of patients had been defined: Groups A and B were comprised of patients treated with either "higher" doses of complexes (Group A) or "lower" doses (Group B), whereas Group C received the placebo preparation. Four injections of complexes were performed during the third yr and none during the fourth yr. The clinical benefit resulting from such injections was maintained until the end of the study, whereas medication intake, especially systemic or high doses of inhaled corticosteroids, was much reduced. Skin reactivity to allergen was significantly decreased in both treated groups. Bronchial provocation tests were carried out at 1-yr intervals with either allergen or acetylcholine (ACh). Reactivity to allergen inhalation was significantly decreased at each time point. Reactivity to ACh was significantly decreased at the end of Years 3 and 4. Fifty percent of treated patients who underwent bronchial challenges lost their bronchial reactivity to the highest concentrations of both allergen and ACh. A significant improvement in the basal lung function was observed in both treated groups. The long-term effects of immunotherapy with allergen-antibody complexes in allergic asthma patients thus include reduction in nonspecific bronchial reactivity. To evaluate the efficacy and safety of immunotherapy (hyposensitisation) in patients with severe summer hay fever.
                A randomised, double blind, placebo controlled study of a biologically standardised depot grass pollen extract.
                Allergy clinic, Royal Brompton and National Heart Hospital, London.
                40 adults (mean age 35 years) with a history of severe grass pollen allergy uncontrolled by standard antiallergic drugs. Patients with perennial asthma were specifically excluded.
                Patients were randomised to receive either an active preparation (Alutard SQ, a grass pollen (Phleum pratense) extract) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached. This maintenance dose was given once a month.
                Clinical efficacy was evaluated by symptom and drug diary cards, visual analogue scores during the grass pollen season, and a postseasonal assessment by the patients and a doctor. Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment.
                There was a highly significant decrease (median Alutard SQ v median placebo (95% confidence interval for difference between medians] in total symptom scores (p=0.001) in the Alutard SQ treated group (360 v 928 (238 to 825]. Significant differences were also found in total drug use (p=0.002, 129 v 627 (178 to 574]. Visual analogue symptom scores were also reduced in the active group (p=0.02, 2.2 v 5.5 (-4.8 to -0.5]. The postseasonal assessment, by either the doctor or the patients, showed a large improvement (p less than 0.001) in favour of Alutard SQ. Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity (p=0.001), a 40% decrease in early phase response (p=0.02), and a 57% decrease in the late phase (p=0.001) cutaneous response after intradermal allergen. A total of 523 active injections were given. There was one systemic reaction at 10 minutes after injection, which was rapidly reversed with intramuscular adrenaline. There was one mild delayed urticarial reaction at 2 1/2 hours.
                Immunotherapy is effective in patients with severe summer hay fever, but immediate anaphylactic reactions limit its use to specialised centres. Patient selection is extremely important, and chronic perennial asthma should be specifically excluded. As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary. We have prepared antigen-antibody complexes from grass pollen allergens and autologous specific antibodies isolated by immunoadsorption from the serum of allergic patients. These complexes were inoculated into patients in a double-blind trial to evaluate their effect on grass pollen-related rhinitis and bronchial asthma. Thirty-eight grass pollen-hypersensitive patients were allocated to three groups; patients in the first two groups were treated with antigen-antibody complexes at different ratios and dosages and were compared with the third group who received the placebo carrier buffer alone. In addition, we treated a fourth group who had already received antigen-antibody complex inoculation during the previous pollen season. Injections were given every 2 weeks during the pollen season, starting 5 weeks prior to it. Tolerance was excellent with no signs of local or systemic side effects. The treatment prevented nasal symptoms while enabling the patients to reduce antihistamine intake. Bronchial asthma was virtually absent in the treated groups even though no bronchodilators or corticosteroids had to be taken. Specific IgE antibodies did not increase during the pollen season nor did IgG "blocking" antibodies. Inoculation of allergen-antibody complexes could provide a valuable alternative for the treatment of immediate hypersensitivity to airborne allergens as it appears to be safe and rapidly efficacious. This treatment offers several advantages compared to conventional hyposensitization and is characterized by the absence of an increase in specific IgG antibodies. Clinical manifestations after the inhalation of Olea europaea pollen are very frequent in Spain. Forty-five patients with a clinical history of asthma and sensitivity to O. europaea pollen were included in a randomized trial to evaluate the safety and the clinical efficacy of immunotherapy with a new chemically modified extract (depigmented and glutaraldehyde-polymerized) of Olea europaea. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into three groups of 15 individuals: Group A received a maximum concentration of 44 micrograms/ml of the depigmented, polymerized allergen extract (equivalent to 100 HEPL of the native unmodified extract). Group B received 10 times less; Group C did not receive any specific immunotherapy. Any adverse event was recorded to assess safety. Efficacy was evaluated by measuring the amount of allergen needed to elicit a positive response in specific bronchial challenges before and after 12 months of immunotherapy. The treatment schedule consisted of an incremental phase of five injections and a maintenance dosage of 0.5 ml per month. Each patient received a total of 14 injections during this period. No moderate or serious adverse events related to immunotherapy were recorded. At the beginning of the study, no significant differences were observed between the three groups in specific bronchial hyperreactivity (p > 0.05). A significant difference (p < 0.05) was obtained after 12 months. Patients in Group A needed four times more native unmodified allergen than Group C to elicit the same degree of bronchoconstriction. The analysis of the individual groups before and after 12 months of treatment showed that patients in Groups B and C did not improve. Patients in Group A showed a significant improvement (p < 0.05) in specific bronchial hyperreactivity, and at the end of the study needed 5.5 times more native unmodified allergen to obtain the same degree of bronchial response as in the beginning. Depigmented and glutaraldehyde-polymerized vaccines of Olea europaea pollen are very safe for treating patients with asthma and clinical sensitivity to allergens of this pollen. The clinical efficacy of this new allergen vaccine seems to be dose-dependent as shown by specific bronchial challenges as well as by symptom and medication scores. These modified extracts induce protection against unmodified native allergens. Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3-year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus (D pt) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM).
                A randomized clinical trial was performed after 1-year run-in period. Fifteen children receiving SIT for HDM and 14 controls (four drop-outs), matched for age, allergen sensitization, asthma severity, lung function, and non-specific bronchial reactivity (BHR), were studied during the 3-year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study.
                In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non-specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side-effects were reported during the study.
                Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects. To assess the efficacy of specific immunotherapy with standardized cat dander extract, using objective endpoints and simulated 'natural' exposure to cats.
                Double-blind, randomized, placebo-controlled study carried out at a UK Allergy research clinic.
                Twenty-eight patients with moderate to severe allergic rhinoconjunctivitis with asthma due to cat allergy. Subjects were stratified for cat sensitivity, cat ownership and asthma, and the groups were well matched for all relevant parameters.
                Symptom scores and peak flow rate during and after exposure to cats in a cat-room. Skin tests and conjunctival provocation thresholds.
                The actively treated group showed a marked reduction in symptoms during the cat exposure (mean score 61.6-17.1; P < 0.001) with no change in the placebo group (64.7 vs 62.1). The active group also showed a reduced peak flow response to cat exposure (mean fall of 85 L/min pretreatment, 29 L/min after treatment, P < 0.005) as well as reductions in conjunctival provocation sensitivity, skin sensitivity to cat extract and skin sensitivity to house dust mite (D.pteronyssinus). Skin reactivity to histamine and codeine were unaltered. No significant adverse reactions were encountered.
                Specific immunotherapy seems to be an effective treatment for cat allergy. Allergy to cats is common and often poorly controlled on conventional pharmacotherapy. Although cat allergy has not traditionally been considered as a valid indication for immunotherapy in the UK, it should now be considered as a legitimate treatment, especially for those who are unable to avoid exposure. nan 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. The present study was designed to investigate the effects of immunotherapy (IT) with an extract of Dermatophagoides pteronyssinus (Alergo-Merck Depot) during a 27-month period in patients with allergic asthma to house-dust mites. We included 11 patients (mean age 18 years) treated with a combination of IT and inhaled beclomethasone dipropionate (BDP) in comparison to another 11 (mean age 22 years) treated with BDP alone. We evaluated symptom scores, salbutamol use, peak expiratory flow rates (PEFR), spirometry, and bronchial hyperresponsiveness (BHR) during 18 months of therapy with BDP and in the 9 months after BDP interruption. The two kinds of treatment were efficient and comparable in relation to symptom score, salbutamol use, morning PEFR, FVC, and FEV1, but patients treated with IT and BDP had a faster improvement of BHR and PEFR variability. The interruption of BDP after 18 months of therapy was linked to an impairment of all end points, which were more pronounced in patients previously treated only with BDP. These findings suggest that in selected asthmatic patients allergic to house-dust mites, the association of IT and BDP is more effective than therapy with this inhaled steroid alone due to a faster and more striking improvement during the first months of treatment and to a lower rate of relapse after the interruption of therapy with BDP. 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. 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). We designed a cluster schedule of immunotherapy for patients allergic to Dermatophagoides pteronyssinus to reach the maximal recommended dose in 7 weeks. We compared its safety and clinical efficacy with those of a conventional schedule in a controlled trial. Sixty-three patients were randomized as follows: 29 were treated with the cluster schedule, 15 with a conventional schedule and 19 without immunotherapy. A standardized extract was used. Clinical efficacy was measured by visual analog scale, clinical severity score, symptom/medication diary cards and control of peak expiratory flow (PEF) in asthmatic patients, before immunotherapy (T0), on reaching the maintenance phase (T1), and after 6 (T2), 12 (T3) and 18 months of maintenance (T4). The safety of immunotherapy was found to be good. Visual analog scale improved significantly at T4 in the cluster and conventional schedules, and clinical severity score also improved from T1 in these schedules. Diary cards improved from T1 in the cluster schedule and from T2 in the conventional schedule in asthmatic patients. Significant improvements in diary cards in rhinitis patients and PEF were found only in the cluster schedule. There were no changes in the group without immunotherapy. In conclusion, our cluster schedule showed as good tolerance and clinical efficacy as the conventional schedule in patients allergic to D. pteronyssinus. These clinical improvements did not appear in the group without immunotherapy. The efficacy of allergen immunotherapy using depigmented and polymerized extracts has been previously shown for Olea europaea, Phleum pratense, and Parietaria judaica. The objective of this study was to evaluate the efficacy after 3 and 6 months of treatment of a depigmented, polymerized extract of a mixture of Dermatophagoides pteronyssinus and D. farinae.
                A group of 22 patients suffering from asthma and monosensitized to mites was treated with the mixture of modified allergen extract. A group of 11 mite-sensitive, asthmatic patients receiving only pharmacological treatment was used as control. The study was open, parallel, controlled, and random-allocated. Objective and subjective criteria, such as changes in D. pteronyssinus-specific bronchial hyperreactivity, visual scale, and medication/symptom scores were used to evaluate efficacy. Each patient received a built-up phase of 6 injections in 5 weeks, followed by 5 injections of the maintenance dose, which consisted of 42.5 micrograms of depigmented, polymerized extract of D. pteronyssinus and 32.5 of D. farinae. The Friedman test was used to compare the results of the specific bronchial challenges at baseline and after 3 and 6 months of treatment.
                A significant difference in the amount of native extract of D. pteronyssinus needed to produce a drop of 20% in the FEV1 (p = 0.0029) in the immunotherapy-treated group was found. In this group, the median allergen potency needed at baseline was 0.6 HEP (35 micrograms) vs. 3.96 HEP (232 micrograms) at the end of the study, whereas no difference (median 0.6 vs. 0.57 HEP) was found in the control group. At the end of the study, 10 patients in the immunotherapy treated group vs. 1 in the control group needed more than twice the amount of allergen than at baseline to experience a 20% drop in FEV1 (p = 0.03). Symptom and medication scores and visual scale evaluation did also show a significant improvement after 3 and 6 months of treatment only in active group. A significant decrease in skin test reactivity was also detected in the active group after 6 months, which needed a median of 3 times more allergen to elicit the same reaction as histamine (10 HEP) (p = 0.028), whereas no changes were found in control group. No serious side effects were registered.
                Depigmented polymerized extracts of D. pteronyssinus and D. farinae are safe and effective in the treatment of mite allergic asthmatic patients, and provide clinical benefit in the shock organ after 6 months of treatment. Skin test reactivity, symptom and medication scores were also improved. Depigmented polymerized extracts of D. pteronyssinus and D. farinae induce clinical protection against a native extract as verified by specific bronchial challenges. nan 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. Thirty-nine ragweed-allergic seasonal asthmatics were studied from 1972 to 1974. After quantitative skin tests, antigen E-induced leukocyte histamine release, quantitative inhalation bronchial challenge with ragweed extract to determine PD35 (provocation dose of allergen causing 35% decrease in specific airways conductance), and radioallergosorbent test (RAST) determinations were done, patients were paired based on PD35 values and randomly assigned to treatment or placebo groups, receiving either aqueous ragweed extract or placebo prior to the 1973 ragweed season. Treated patients received a mean cumulative dose of extract equivalent to 11.7 microng antigen E (4,180 protein nitrogen units [PNU]). Twenty-nine patients were followed through the ragweed season with daily symptom diaries and biweekly physician examinations. Severity of disease was not predictable by PD35 data, skin tests, leukocyte histamine release, or radioallergosorbent test (RAST) values. Although all patients were ragweed-allergic by objective tests, only 13/29 had asthma symptoms correlating with ragweed counts. Mold spore counts were related significantly to symptoms in some patients. Asthma and hay fever symptoms correlated significantly in 24/29 patients. This dose of immunotherapy caused no significant difference to be found in asthma or hay fever symptoms in treated versus placebo patients for the 1973 reporting period as determined by physician evaluations or daily symptom diaries. No patients showed significant improvement in PD35 values after treatment in 1973. Similar findings were obtained for a smaller group of patients followed through the 1974 ragweed season who received a mean dose of 31.2 microng antigen E (11,140 PNU). The failure of these patients to show a response to immunotherapy could be due to a combination of the relatively low dose of ragweed extract and their sensitivity to other allergens. 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. 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. Rush immunotherapy (RIT) has been shown to be effective in allergic asthma.
                We investigated the mechanisms of RIT on the basis of cytokine production by T-cell lines and airway inflammation and responsiveness.
                Subjects were 8 patients with house dust mite-allergic asthma treated with dust mite extract RIT for 6 months and 6 RIT-untreated control patients. IL-5 production by Dermatophagoides farinae -specific T-cell lines, eosinophil percentages, and eosinophil cationic protein (ECP) in induced sputum and airway responsiveness to allergen and histamine were evaluated before and after treatment. Changes in eosinophil percentages and ECP in induced sputum and responsiveness to histamine 24 hours after allergen inhalation were also studied.
                After 6 months of RIT, percentages of total eosinophils (43. 0% +/- 6.90% to 16.8% +/- 2.48%; P <.01), percentages of EG2(+ ) eosinophils (32.6% +/- 6.39% to 19.7% +/- 4.68%; P <.01) and ECP (362.7 +/- 125.3 ng/mL to 26.2 +/- 5.15 ng/mL; P <.05) decreased in induced sputum, and IL-5 production by T-cell lines decreased (617 +/- 93.2 pg/mL to 200.0 +/- 34.1 pg/mL; P <.01). RIT decreased both early- and late-phase bronchoconstriction (early phase: 33.2% +/- 3. 46% to 25.4% +/- 1.42%; P <.03; late phase: 16.2% +/- 3.52% to 6.2% +/- 1.96%; P <.03) and suppressed increases in the percentages of total (61.8% +/- 4.89% to 42.0% +/- 4.67%; P <.01) and EG2-positive eosinophils (55.54% +/- 7.21% to 36.5% +/- 6.43%; P <.01) and ECP (685.6 +/- 217.0 ng/mL to 85.4 +/- 23.4 ng/mL; P <.05) in induced sputum after allergen inhalation. RIT also decreased airway responsiveness to dust mite (1:303.7 +/- 123.7 wt/vol to 1:65.0 +/- 13.2 wt/vol; P <.03) and to histamine before (397.1 +/- 206.9 microgra/mL to 1391.3 +/- 283.3 microgram/mL; P <.03) and after allergen inhalation (139.2 +/- 36.5 microgram/mL to 629.1 +/- 196.3 microgram/mL; P <.03).
                RIT decreases airway inflammation and airway hyperresponsiveness before and after bronchial provocation with allergen, possibly by inhibiting both allergen-specific T-cell- and mast cell-dependent pathways. RIT is an effective antiinflammatory treatment in allergic asthma. 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. dermatophagoides pteronyssinus (Der PI) is the major allergen which causes allergic asthma and perennial rhinitis. The extracts of Der PI may be used in treatment of patients who are unresponsive to pharmacological treatment and avoidance of allergens. The success of immunotherapy (IT) depends on the selection of appropriate patients and allergens as well as a regular follow up.
                three different groups of IT materials and a placebo were tested on 34 patients with Der PI sensitive asthma. Clinical evaluations of allergen challenge and in vitro immunologic tests were made on the patients before, on the 6th month and at the end of the second year of IT. The results were compared to the placebo treated group.
                there were no significant differences among the groups in regard to age, sex and duration of illness. The time required for reaching the maintenance dose for group I (Alutard), II (APSI retard Ca) and III (Greer ) was 15.40 +/- 0.69, 18.2 +/- 4.0 and 108 +/- 33 weeks, respectively. Even though there was some significant difference between those receiving aqueous IT and the placebo (p < 0.05), there was a greater significant difference between those receiving adsorbed IT and placebo (p < 0.00001). Also there was a significant difference between the I and II groups receiving adsorbed IT. There was no significant difference in the maximum tolerated doses between group I and II (p > 0.05), but significant differences was found between group III and the other two groups (p < 0.05). Specific IgE levels were not changed by IT. There were no differences in the side effects scores among the groups (p < 0.05). The maximum tolerated dose of the diluted skin prick test (DSPT) solution increased significantly after 6 months and two years treatment as compared to the dose before specific immunotheraphy (SIT). Significant differences were found between group III and group I or group II as well as between the groups under treatment and that group given a placebo (p < 0.05). The maximum tolerated dose with the bronchial provocation test (BPT) increased significantly after IT (p < 0.05). The differences between the groups under treatment and that given a placebo were significant (p < 0.05). A significant increase was detected in the levels of the Der PI specific IgG4 after IT (p < 0.01). The difference between the treatment groups and the placebo group was significant. There was a significant difference between group I and the other groups (p < 0. 05) but differences between group II and III was not significant (p > 0.05). No significant correlation was found between (1) spIgE and the symptom medication score (SMS) (2) sp IgE and spIgG4 (3), DSPT and BPT. A significant positive correlation was found between the maximum tolerated dose with DSPT and increase in spIgG4 (r = 0.33, p = 0.046). A negative correlation was found between SMS and spIgG4 (p = 0.012, r = -0.42) after IT.
                SIT with Der PI is an effective and reliable treatment in allergic asthmatic children. Adsorbed extracts may be preferable to in childhood because of effectively, safety, tolerability and, fewer numbers of injection. The best IgG4 response and velocity of maintenance doses achieved was found in group I. Easy, cheap and safe parameters such a SMS and DSPT can be useful for a follow-up of SIT. Further investigation is required to determine which one of the products is the best. Twenty asthmatic children with laboratory proved bronchial reactivity to rye-grass pollen were studied over two consecutive grass-pollen seasons. In the first year 11 patients received preseasonal hyposensitisation treatment with an aqueous rye extract and nine received placebo injections. No treatment was given in the second year. Patients in both the active-treatment and placebo groups showed a pronounced clinical deterioration in their asthma during both pollen seasons. Serum concentrations of IgG-specific antibodies to the rye allergen before treatment were similar in both groups, but after immunotherapy and before the pollen season in the first year these antibody concentrations were raised significantly in the treated group (p less than 0.005): by the middle of the pollen seasons the difference was no longer significant. IgE-specific antibodies showed a similar but nonsignificant pattern of response. We found no evidence that limited hyposensitisation with a pollen extract is of any clinical benefit in seasonal asthma despite evidence of an immunological response. Hypersensitivity to dogs and cats causes asthma in many children. In this open controlled clinical study we wanted to establish whether immunotherapy can be recommended as a supplement to conventional medical therapy in dog- and cat-induced asthma in children. Twenty-seven children with mean age 10 7/12 years and with allergy to dog or cat according to anamnesis, skin prick test (SPT), specific IgE (RAST) and bronchial provocation test (BPT) entered the study. On the basis of age and bronchial sensitivity they were randomly allocated to either immunotherapy with dog or cat extract (active group, n = 14) or conventional medical therapy (control group, n = 13). Immunotherapy comprised subcutaneous injections with an alum-adsorbed depot extract (Alutard-SQ), and a maintenance dose of 100,000 SQ-U or the maximum tolerated dose. Before entering the study and after 9 months' therapy the patients were evaluated by BPT, SPT, RAST - and IgG4 analyses. The active group showed statistically significant change in bronchial tolerance (P less than 0.02), whereas no such change was found in the control group (P greater than 0.05). The change in skin sensitivity was significantly greater in the active group than in the control group (P less than 0.05), whereas no significant differences were found in RAST and IgG4. However, a significant (P = 0.05) increase in IgG4 was seen in the active but not in the control group. Frequency and degree of side effects in this study were acceptable.
Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity.  One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.