Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization. Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study. Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis. Allergen-specific immunotherapy with recombinant grass pollen allergens. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. Immunotherapy with depigmented glutaraldehyde-polymerized extracts: changes in quality of life. Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial. Allergen-antibody complexes can efficiently prevent seasonal rhinitis and asthma in grass pollen hypersensitive patients. Allergen-antibody complex immunotherapy. Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study. A controlled trial of immunotherapy for asthma in allergic children. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma--a placebo controlled study. The role of patient training in the management of seasonal rhinitis and asthma: clinical implications. Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity. Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites. A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. Comparison between the use of adsorbed and aqueous immunotherapy material in Dermatophagoides pteronyssinus sensitive asthmatic children. A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship. Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Immunotherapy with Alpare in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study. 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. Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract. Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis. Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite. A double-blind study. Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing. Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: a randomized study. Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: A double-blind, placebo-controlled trial. Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite. A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract. Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy. Double-blind, placebo-controlled study of immunotherapy with Parietaria judaica: clinical efficacy and tolerance. [Clinical evaluation for sublingual immunotherapy of allergic asthma and atopic rhinitis with Dermatophagoides Farinae Drops]. Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis.
We investigated the effects of immunotherapy (IT) on the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge with antigen as well as on the cutaneous ER and LPR to intradermal skin challenge. Our expectation was that IT would have a preferential effect on the LPR, and our aim was to understand the mechanism. Twenty-one ragweed hay fever-sensitive subjects were treated with a moderate dose of antigen extract (maintenance dose of 1.94 micrograms of antigen E (Amb a I)) during a period of 8 months (total dose equivalent to 24 micrograms of antigen E), and 20 matched subjects received placebo injections in a double-blind manner. Both groups underwent identical nasal challenges and intradermal skin tests with ragweed-antigen extract both before (1985) and during (1986) IT. Symptom and medication diaries, recorded during seasonal exposure, and changes in specific serum IgE and IgG antibodies confirmed the efficacy of the administered IT dose. Between-group analysis revealed that IT significantly reduced the levels of histamine, TAME-esterase activity, and kinins, as well as symptoms of rhinorrhea and congestion generated during the ER to nasal challenge. Within-group paired analysis demonstrated ER, LPR, and RCR mediators and symptoms also to be reduced by IT. Surprisingly, the placebo-treated group demonstrated an increase in the ER. There was no decrease of the LPR without an antecedent decrease of the ER. IT did not clearly change the late cellular inflammatory response. In the case of skin challenge, IT significantly reduced the cutaneous ER. The reduction of the cutaneous LPR was more pronounced. We speculate that moderate-dose IT ameliorates seasonal symptoms of allergic rhinitis by reducing the ER, LPR, and RCR to antigen challenge but does not preferentially reduce the nasal LPR. Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed.
                We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy.
                We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms.
                Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000-SQ-U group compared with those in the placebo group (both P < .001). Over the peak pollen season, mean symptom and medication scores were 32% and 41% lower, respectively, than those in the placebo group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over the whole season (P < .01), but medication scores reduced by only 16% (P = .16). Quality-of-life measures confirmed the superiority of both doses to placebo. Local and delayed side effects were common but generally mild. Clinically significant early and delayed systemic side effects were confined to the 100,000-SQ-U group, but no life-threatening reactions occurred.
                One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever. The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen caused fewer side effects. A double-blind, placebo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica-pollen allergoid, Allergovit, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8-9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria-pollen-induced rhinitis or asthma. 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. For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization. The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity.
                A single-center, randomized, double-blind, placebo-controlled study was performed. Patients were selected and randomly allocated to two groups: one group received active treatment (allergoid SLIT) for 2 years and the other received placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years' treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group.
                The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen. Seasonal allergic rhinitis is common and troublesome. Sublingual immunotherapy (SLIT) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting.
                To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current standard medication. To assess the feasibility of delivering SLIT in a United Kingdom general practice setting.
                Double-blind, placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practices. After a baseline year to ensure balanced groups, subjects were randomized, and SLIT was given for 1 or 2 years and compared with placebo. The principal outcome measure was symptoms as recorded on diary cards. Secondary criteria were skin and conjunctival reactivity, allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects.
                One hundred thirty-six subjects completed the study. After 1 year, no significant differences were found between actively treated subjects and the placebo group. After the second year of therapy, subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running (P <.001) and 2.4 times more likely to have reduced sneezing (P <.05) compared with subjects in the placebo group. Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups.
                Sublingual immunotherapy can be given successfully and safely in the community. High-dose SLIT has beneficial effects on nasal symptoms during the peak pollen season in patients with severe seasonal allergic rhinitis. At least 2 years of treatment with SLIT is required to show a benefit. Allergen-specific immunotherapy uses aqueous extracts of natural source materials as a basis for preparations to down regulate the allergic response. Recombinant DNA technology has enabled the cloning of many allergens, thus facilitating investigations aimed at improving efficacy and safety of immunotherapy.
                To determine the effectiveness of a mixture of 5 recombinant grass pollen allergens in reducing symptoms and need for symptomatic medication in patients allergic to grass pollen.
                A randomized, double-blind, placebo-controlled study of subcutaneous injection immunotherapy was performed in subjects with allergic rhinoconjunctivitis, with or without asthma. Primary endpoint was a symptom medication score compiled from separate symptom and medication scores. Secondary endpoints included a rhinitis quality of life questionnaire, conjunctival provocation, and specific antibody responses.
                The symptom medication score showed significant improvements in subjects receiving recombinant allergens as opposed to placebo, with reductions in both symptoms and medication usage. The rhinitis quality of life questionnaire revealed clinically relevant significant improvements in overall assessment and in 5 of 7 separate domains, and conjunctival provocation showed a clear trend in favor of active treatment. All treated subjects developed strong allergen-specific IgG(1) and IgG(4) antibody responses. Some patients were not sensitized to Ph l p 5 but nevertheless developed strong IgG antibody responses to that allergen.
                A recombinant allergen vaccine can be a effective and safe treatment to ameliorate symptoms of allergic rhinitis. The clinical benefit is associated with modification of the specific immune response with promotion of IgG(4) and reduction of IgE antibodies consistent with the induction of IL-10-producing regulatory T cells. 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. Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well-being) induced by a modified (depigmented glutaraldehyde-polymerized) therapeutic vaccine and of its safety.
                Fifty-three patients with a well-documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty-five patients (Group-A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group-C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose-response skin prick test with each allergen extract was conducted at baseline and at the end of the study.
                Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of 'minimal important difference' of 0.5 points.
                Results of this study provided evidence that IT with depigmented, glutaraldehyde-modified allergen extracts was well-tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment. 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. 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. Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper (Allergen immunotherapy: therapeutic vaccines for allergic diseases) "as a viable alternative to parenteral injection therapy to treat allergic diseases" in adults. More controlled studies were required to assess the efficacy and safety of this treatment in children.
                This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies.
                We used a double-blind placebo-controlled design. Forty-one children with Parietaria -induced rhinoconjunctivitis were randomized to receive sublingual standardized Parietaria judaica extract (n = 20) or placebo (n = 21) for 2 years. The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years. The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients' diary cards. Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters, analyzed after 1 and 2 years of immunotherapy. The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects.
                A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season (P =.02), with no difference in medication scores. A significant decrease in skin reactivity (P =.002 after 2 years of treatment) and an increase in the threshold dose for conjunctival allergen provocation test (P =.02) were observed in the active treatment group compared with the group receiving placebo. A significant increase in specific IgG(4 ) levels (P =.02) was also observed in the active group. Immunotherapy was well tolerated.
                Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen. The safety profile of this treatment, which constitutes an important issue, indicated good tolerance and compliance. Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking.
                The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis.
                A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season.
                The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events.
                Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects.
                The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use. A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed. 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. 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. Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms.
                One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season.
                The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02).
                Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs. 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. Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy.
                We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment.
                We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months (p=0.05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group (p=0.04 and p=0.02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0.02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0.04). Immunotherapy was well tolerated and compliance was good.
                Our results suggest that this immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen. Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition.
                To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis.
                In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5-grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments.
                Both the 300-index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 +/- 3.0, P = .0001; and 3.74 +/- 3.1, P = .0006, respectively) compared with placebo (4.93 +/- 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 +/- 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported.
                In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo.
                The risk-benefit ratio favors the use of 300-IR tablets for clinical practice. The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial.
                The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well.
                Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%).
                Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease. 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. 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. There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases.
                This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/ investigator), symptoms and medication scores as well as the frequency of asthma attacks.
                In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages.
                This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.
                Copyright 2003 S. Karger AG, Basel Recent studies have demonstrated the efficacy of sublingual-swallow immunotherapy (SLIT) in seasonal and perennial rhinitis. Sublingual administration of solutions is not convenient for all patients. The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually, initially as drops, and then as tablets during maintenance therapy.
                A total of 126 patients with grass-pollen seasonal rhinitis were included in this double-blind, randomized, placebo-controlled trial. During the progression of doses phase, the five-grass extract was given as sublingual drops from 1 to 100 IR/ml. Once the 100 IR dose was reached, the drops were replaced by a single 100-IR sublingual tablet per day.
                Throughout the grass-pollen season, patients in the active treatment group had significantly lower (P < 0.05) total conjunctivitis and ocular redness scores. Rhinitis symptoms were not significantly different between the two groups. Patients given the active treatment were significantly (P < O.02) less likely to have asthma symptoms. The global medication score showed no significant difference between the two groups. A highly significant difference in favor of the active treatment group was seen in inhaled salbutamol use (P < 0.01).
                Clinical benefits achieved during the present study included significant improvements in conjunctivitis symptoms and prevention of asthma symptoms. The overall safety profile of the active treatment (drops or tablets) was good. Allergy to Parietaria judaica pollen causes significant morbidity in many areas of the world. In addition to rhinitis, patients who are allergic to this pollen have a high incidence of asthma. The pollinating season is long, making this particular allergy challenging for clinicians to treat. This study was designed to determine if immunotherapy with an alum adsorbed partially purified Parietaria extract (Alpare Parietaria) containing a targeted maintenance dose of 12,500 BUs was effective in decreasing rhinitis symptoms in patients allergic to Parietaria. Using a double-blind placebo-controlled technique 36 patients received placebo or active extract for 2 years. Twenty (11 placebo and nine active) completed the 2 year study. Efficacy of treatment was evaluated by determining changes in skin reactivity, visual analog scores, diary symptom scores and end of study assessments. Reactions were monitored as well. Skin-test suppression was marginally significant in the actively treated group after 1 year and showed even more significant suppression after the second year. Nasal block, rhinorrhoea and sneezing all were significantly decreased in the active group. The nasal provocation test did not show a significant change after 1 year, in either group, but after 2 years of treatment the active group did show significant improvement. Although almost all patients in the actively treated group experienced local reactions, the incidence of systemic reactions was not different between the two groups. In conclusion, immunotherapy with this extract at this dose was effective in ameliorated rhinitis symptoms in patients allergic to Parietaria judaica. 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. 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. Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS) Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis.
                We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season.
                We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended.
                Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups.
                The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis. Fifty eight patients under 12 years of age, positive to mites (Dermatophagoides pteronyssinus and D. farinae) according to prick, "in vitro" specific IgE and challenge tests, suffering from asthma and rhinitis, were randomly assigned on a double blind basis to receive per os either a biologically standardized extract of mites (active therapy TA = 30 patients) or a saline buffered solution (placebo = 28 patients). Patients took sublingually increasing doses of the solution, followed by maintenance therapy consisting of 15 drops 3 times a week. The results of the trial were assessed after 12 an 18 months, according to the following parameters: symptom scores recorded in diary cards, total and specific IgE levels, total IgG level, IgG1 and IgG4 levels, lymphocytes underpopulations, nasal challenge test, side effects. During the first 18 months, the patients on active therapy had significantly lower scores (p less than 0.001) and clear variations of rhinomanometric parameters (p less than 0.01); IgG also significantly increased. After 12 months, bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values (p less than 0.05). No statistically significative variation was registered in the placebo group. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint.
                One hundred five patients with rhinitis and/or asthma due to grass and olive sensitization were randomized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season. Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and 2005 (n=85).
                Allergic symptoms were significantly decreased in the active immunotherapy group (P = .004) but not in the placebo group. There were no differences in scores between groups during the 2005 pollen season. Subjective assessments on a visual analog scale and a quality-of-life questionnaire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use (P = .006). The rate of systemic adverse reactions was comparable in the 2 groups. No anaphylactic or severe adverse reactions were reported. Local adverse reactions, which were more common in the active immunotherapy group, were mostly immediate, were limited to the lips and mouth, and did not require treatment.
                Once-daily sublingual immunotherapy without updosing was well tolerated. The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated. Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis-related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three-times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective. The local (noninjection) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy, and their mechanisms of action are currently undergoing investigation.
                We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species.
                Thirty patients with Parietaria species-induced rhinoconjunctivitis (13 with mild intermittent asthma) were randomly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course. We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment.
                The investigated immunotherapy was well tolerated, and no side effects were recorded. A significant reduction of the symptom score (P =.016) and drug intake score (P =. 008) after immunotherapy was observed only in the active group. A decrease of the cumulative score was observed also in the placebo group (P =.046), but the significance was clearly higher (P =.006) in the active group. In the active group a reduction of neutrophils (P =.001), eosinophils (P =.01), and intercellular adhesion molecule 1 expression (P =.04) after specific nasal challenge was also detected.
                The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinically effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen. 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. 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. Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergènes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P < 0.05 to P < 0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P < 0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe. 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) Allergy to Parietaria causes significant morbidity in most Mediterranean areas. The aim of this study is to investigate the efficacy and tolerance of Parietaria depot extract at 25 BU/mL (1.5 microg/mL Par j 1). We performed a multicenter double-blind, placebo-controlled study in rhinitic patients with/without asthma, sensitized to Parietaria. 42 patients followed 20-month immunotherapy. Clinical efficacy was based on symptom and medication scores and the percentage of healthy days (days without symptoms or medication). Severity of asthma/rhinitis scales, visual analogue scale, evaluation of the treatment by doctors and patients, immediate and delayed cutaneous response and quality of life questionnaires were also studied. The active group showed a sustained decrease in symptoms (p = 0.008), medication (p = 0.009) and both (p = 0.001), and an increase in healthy days (p = 0.001) throughout the study, with a threefold increase of healthy days and almost a three time reduction in medication only after one year of treatment. Asthma and rhinitis severity scales also decreased after immunotherapy, and blinded clinical evaluation by physicians confirmed efficacy in 85% and 77% of the active patients. Patient's self-evaluation returned similar results. None of these changes were observed with placebo. Immediate cutaneous response was significantly reduced at the maintenance phase in the active group and remained reduced throughout the study. Late-phase response after intradermal testing also showed a statistical decrease in actively treated patients. Immunotherapy was well tolerated and every systemic reaction reported was mild. In conclusion, immunotherapy with Parietaria 25 BU/mL is an effective and safe treatment for patients with respiratory allergies. To evaluate the safety and efficacy of sublingual immunotherapy with 'Dermatophagoides Farinae Drops' in D. farinae allergic asthma and/or rhinitis patients.
                A 25-week double-blind, placebo-controlled, multi-centered trail was conducted in 278 children (aged 4 - 18 yr) with mite-induced asthma and/or rhinitis. Patients were randomly assigned to receive sublingual immunotherapy (SLIT) with 'Dermatophagoides Farinae Drops' (n = 139) or placebo (n = 139) for 25 weeks and the dosage and administration strictly followed the manufacturer's instructions. At the beginning of the 2nd, 3rd, 4th, 6th, 10th, 14th, 18th, 22nd week of the treatment, the patients were asked to accept follow-up visit, during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores, rescue medicine use, rhinitis symptom scores, morning and evening peak expiratory flow. Asthma symptom scores, reduction in use of rescue medicine, rhinitis symptom scores, lung function tests, skin sensitivity to mite, mite-specific immunoglobulin (Ig) E and IgG4, and quality of life and adverse effect were assessed during the study.
                (1) Of the 278 children, 27 dropped out before the study completion. (2) After 25 weeks of treatment, the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo (P < 0.05). (3) Besides, the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo (P < 0.05). (4) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo (P < 0.01). (5) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo. (6) After 25 weeks treatment, the increase of D. farinae specific IgE antibody of two groups were similar, while specific IgG4 increased significantly in SLIT compared to the patients in control one (P < 0.01); (7) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash.
                Dermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis. Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized grass-pollen extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the grass-pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the pollen season (P < 0.02). Moreover, at the peak of the pollen season, betamethasone consumption was significantly reduced in the SLIT group (P < 0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group (P < 0.02). IgG4 levels increased significantly in the SLIT group (P < 0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.
This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.