Immunotherapy Group Research Articles

Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy

Background: Birch pollen is a common allergen in northern, central, and eastern Europe. Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal. Long-term, placebo-controlled studies with subcutaneously administered standardized birch pollen extract are lacking. Objective: The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen–allergic patients in a double-blind, placebo-controlled trial. Methods: Forty-nine patients with histories of birch pollen allergy from the upper and lower airways, positive skin prick test and conjunctival provocation test results, and in vitro specific IgE to birch pollen (Betula verrucosa ) extract were included. Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind, randomized, placebo-controlled study. Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season. Results: Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study. The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and 2.1 and 4.3, respectively, in the placebo group. The differences between the groups were significant (P = .05 in 1997 and P = .005 in 1998). The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group (P = .004 for 1997 and P = .004 for 1998). Conclusion: Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen–allergic patients during the pollen season. (J Allergy Clin Immunol 2002;109:777-83.)

The Effect of Japanese Cedar-specific Immunotherapy on Cytokine Production in Peripheral Blood Mononuclear Cells

The most common cause of seasonal allergic rhinitis in Japan is the Japanese cedar (JC). Recently, a pullulan-conjugated antigen (CS-560) has been developed to reduce adverse effects and to enhance the effect of JC-specific immunotherapy (IT). If the mechanism of IT can be fully elucidated and the treatment can be used safely and with specificity, IT should be reconsidered as a superior treatment for JC pollinosis. Thirteen patients with JC pollinosis who received IT were compared to 10 patients who did not receive IT. All patients were followed through two pollen seasons by means of allergy diaries. Peripheral blood mononuclear cells (PBMC) were collected before IT and just before each pollen season, and these were stimulated with pollen extract. The concentrations of IL-4, IL-5, IL-13 and IFN- n in the culture supernatants were determined using an ELISA. Furthermore, messenger (m)RNA expressions of IL-4 and IL-5 from cultured PBMC were also studied. As a result of the allergy diaries, we confirmed the clinical efficacy of CS-560. The symptom-medication scores were significantly decreased by IT. The levels of IL-4, IL-5 and IL-13 declined only in the IT group. However, the level of IFN- n did not change in either group. IL-4 and IL-5 mRNA expressions were inhibited in the IT group compared to that in the non-IT group. In conclusion, specific IT for JC pollinosis using CS-560 clearly modified cytokine expression by PBMC.

免疫療法による花粉症の発症予防とその機序 スギ花粉感作成立個体に対する予防的免疫療法

This study was designed to investigate whether prophylactic immunotherapy for individuals sensitized to Japanese cedar pollen could prevent an outbreak of pollen-induced allergic rhinitis. A total of 13 non-atopic volunteers and 67 patients sensitized to Dermatophagoides farinae (D. farinae) and Japanese cedar pollen were enrolled in the study. Before enrollment in the study, all of the 67 patients had perennial nasal symptoms due to D. farinae, but no seasonal aggravation of nasal symptoms. 32 patients were treated with immunotherapy using standardized D. farinae extracts alone (control group), and the remaining 35 patients were treated with immunotherapy using the same D. farinae extracts and Japanese cedar pollen extracts (immunotherapy group). The following results were derived from the study:1. Prophylactic immunotherapy significantly decreased incidences of the outbreak of seasonal allergic rhinitis due to pollen.2. IL-4 synthesis during the pollen season by peripheral blood T cells stimulated with the cedar pollen allergen were enhanced in the control group, whereas IL-4 synthesis during the season was not enhanced in the immunotherapy group. In particular, IL-4 synthesis during the season did not differ between the non-atopic volunteers and the patients who were treated with prophylactic immunotherapy for more than 3 years.In conclusion, prophylactic immunotherapy could prevent the outbreak of seasonal allergic rhinitis in those who had been sensitized to the pollen. Therefore, it is likely that prophylactic immunotherapy is a new method of decreasing the incidence of seasonal allergic rhinitis in Japan.

Inmunoterapia con un extracto oral de Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusiones sobre parámetros in vivo e in vitro

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.

Inhalant allergy and Meniere's disease: Use of electrocochleography and intranasal allergen challenge as investigational tools

Introduction: In an earlier study, we demonstrated the feasibility of using electrocochleography (ECoG) to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and Meniere's disease, using the antigen to which they were most sensitive. Objective: We expand on this earlier study and continue to investigate the feasibility of this model in a subset of patients with inhalant allergy and Meniere's disease after immunotherapy. Study design: Prospective study of 11 patients identified with both Meniere's disease and inhalant allergy in the practices of 2 neurotologists at our institution. Patients underwent a baseline ECoG, followed by intranasal challenge with the allergen to which they were most sensitive. This was followed by a second ECoG. Results: Six of 11 patients had at least 1 year of immunotherapy (group 1), and 5 of 11 had had 0 to 6 months of immunotherapy (group 2). Four of 6 group 1 patients had a >15% increase in SP/AP ratio after immunotherapy. In group 2, 2 patients increased the SP/AP in at least 1 ear. No patient with a normal ECoG experienced vestibular symptoms after allergen challenge, whereas 2 of group 1 and 2 of group 2 had vestibular symptoms with abnormal ECoGs. Conclusion: This protocol is a useful tool for investigating the relationship of inhalant allergy and Meniere's disease, but needs a larger group of patients and further study to draw valid statistical conclusions. (Otolaryngol Head Neck Surg 2001;125:346-50.)

Grass pollen immunotherapy: Symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season

Background: Tissue eosinophilia and infiltration by TH2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. Objectives: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. Methods: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor–positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. Results: Immunotherapy significantly reduced symptoms (49%, P = .01) and medication requirements (80%, P = .007) compared with placebo. There was a 400% increase (P = .004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P = .04 between groups). Seasonal increases were also observed for CD25+ cells (P = .002), CD3+ cells (P = .02), and IL-5 mRNA–expressing cells (P = .03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P < .05). Both eosinophils (r = 0.6, P < .02) and IL-5 (r = 0.6, P < .02) correlated with symptoms after immunotherapy. Conclusion: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5–dependent tissue eosinophilia during the pollen season. (J Allergy Clin Immunol 2001;107:971-6.)

スギ花粉症に対する１年間の免疫療法 末梢血単核球の抗原反応性の変化

This study was designed to investigate the effect of a single year of immunotherapy on cytokine synthesis by allergen-stimulated peripheral blood mononuclear cells (PBMCs) of patients with seasonal allergic rhinitis. This study included 12 nonatopic subjects (nonatopic group) and 28 patients with seasonal allergic rhinitis due to Japanese cedar pollen. Immediately after the pollen season 1998, 14 patients started receiving immunotherapy (immunotherapy group), and the remaining were treated with antihistamines during the pollen season 1999 (medication group). PBMCs (1.0×106 cells/mL) were obtained from each subject before and during the pollen season 1999, and cultured for 96 hours in the absence of and in the presence of 10μg/mL of Cry j 1. The levels of IL-4, IL-5 and IFN-γ in the supernatants were determined using enzyme-linked immunosorbent assay (ELISA). Seasonal increase in Cry j 1-specific IL-4 and IL-5 synthesis was significant in the medication group and in the immunotherapy group, but not in the nonatopic group. Although the levels of Cry j 1-dependent IL-4 and IL-5 before the pollen season did not differ significantly between the untreated group and the immunotherapy group, the levels of Cry j 1-dependent IL-4 and IL-5 during the pollen season were significantly lower in the immunotherapy group than in the untreated group. The levels of Cry j 1-dependent IL-4 before as well as during the pollen season did not differed significantly between the good and poor responders to immunotherapy, whereas the levels of Cry j 1-dependent IL-5 during the pollen season were significantly lower in the good responders than in the poor responders to immunotherapy. Therefore, we concluded that the suppression of Cry j 1-dependent IL-5-producing Th2 cells during the pollen season is a major working mechanism of a single year of immunotherapy for seasonal allergic rhinitis due to Japanese cedar pollen.

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

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

Grass pollen immunotherapy for seasonal rhinitis and asthma: A randomized, controlled trial

Background: Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements. Effects on seasonal asthma are less clear, and concerns over safety persist. Objective: 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. Methods: 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. Results: 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 PC20 (provocation concentration producing a 20% fall in FEV1) 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. Conclusion: Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness. (J Allergy Clin Immunol 2001;107:87-93.)

Adverse influence of numbers of previous miscarriages on results of paternal lymphocyte immunization in patients with recurrent spontaneous abortions.

To determine whether an increase in the number of previous miscarriages in recurrent spontaneous abortion patients is a risk factor in subsequent pregnancies with paternal lymphocyte immunotherapy. Live birth rates with reference to previous abortion numbers in recurrent spontaneous abortion patients were statistically compared between paternal lymphocyte immunotherapy and control groups, the latter retrospectively researched using historical data before 1981 in our clinic. The overall live birth rate was 73% (169/232) in the immunotherapy group, and 48% (47/97) in controls (P <0.05). According to previous abortion numbers, the rates were 77% (114/148) versus 55% (36/65) (P < 0.05) for three previous abortions, 70% (40/57) versus 38% (8/21) (P < 0.05) for four and 56% (15/27) versus 27% (3/11) (not significant) for five, in the study and control groups, respectively. The results confirm the efficacy of paternal lymphocyte immunotherapy, but demonstrate that the success rate deteriorates with the number of previous miscarriages.

Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial

Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence. Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat. 76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45 [59%] vs 57 [77%]) [corrected] patients. Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantly longer recurrence-free survival (p=0.01) and disease-specific survival (p=0.04) than the control group. Overall survival did not differ significantly between groups (p=0.09). Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.

Changes in Cytokine Production In Vitro during the Early Phase of Birch‐Pollen Immunotherapy

The kinetics of the immunological mechanisms during allergen-specific immunotherapy (IT) has not been thoroughly evaluated. In this investigation we study the changes in T-cell responses during the early phase of IT. Ten patients (IT group) with birch-pollen allergy were treated with conventional IT. Blood samples were collected at regular intervals for specific immunoglobulin (Ig)E measurements and preparation of peripheral blood mononuclear cells (PBMC). Seven allergic control patients (AC group) were included during the subsequent birch-pollen season. The PBMC were stimulated with birch-pollen extract or tetanus toxoid (TT) and mitogens. After a short decrease, probably owing to seasonal variation, the birch-pollen-specific proliferation and the interleukin (IL)-4, IL-5, and IL-10 production significantly increased when reaching the maintenance dose and during the subsequent pollen season. The increase in IL-4 correlated with a temporary increased serum level of birch-pollen-specific IgE. Interestingly, also the TT-specific response was affected by IT, resulting in weaker, but in time similar, changes in proliferation and cytokine production as in the birch-pollen-specific response. We speculate that the early phase of IT might lead to systemic changes in the capacity of Th2-like cytokine production, and that the early increase in allergen-specific IgE is a consequence of enhanced IL-4 production.

Effectiveness of specific immunotherapy in the treatment of asthma: A meta-analysis of prospective, randomized, double-blind, placebo-controlled studies

Despite decades of positive experience with specific immunotherapy (SIT) in the treatment of asthma, outcomes associated with SIT have not been evaluated. This meta-analysis was conducted to compare the effects of SIT plus medical treatment with those of SIT without medical treatment in patients with asthma. All studies of SIT in patients with asthma published in English between the years 1966 and 1998 were identified through a MEDLINE search. All prospective, randomized, double-blind, placebo-controlled studies of SIT identified by the search were included in the meta-analysis. One author (R.N.R.) extracted data from these studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Data were extracted from 24 identified studies of the clinical effectiveness of SIT in the treatment of asthma, involving 962 asthmatic patients with documented allergy. Immunotherapy was judged effective in 17 (71%) of the 24 studies, ineffective in 4 (17%), and equivocal in 3 (12%) (chi2 = 15.25, df = 2, P = 0.0005). Symptoms of asthma were more likely to improve in patients who received SIT than in patients who received placebo (OR 2.76, 95% CI 2.22 to 3.42). Results also favored the immunotherapy group for improvement in pulmonary function (OR 2.87, 95% CI 1.82 to 4.52), protection against bronchial challenge (OR 1.81, 95% CI 1.32 to 2.49), and reduced need for medications (OR 2.00, 95% CI 1.46 to 2.72). The findings of this meta-analysis support the conclusion that SIT is effective in a population of patients with allergen-triggered asthma.

Bacterial vaccines: anything but placebo.

Bacterial vaccines: anything but placebo.

Pollen immunotherapy inhibits T helper 1 and 2 cell responses, but suppression of T helper 2 cell response is a more important mechanism related to the clinical efficacy.

To investigate the allergen-induced IgE synthesis and cytokine production by peripheral blood mononuclear cells from patients with seasonal allergic rhinitis due to Japanese cedar (Cryptomeria japonica) pollens and to elucidate the immunological mechanisms related to the clinical efficacy of immunotherapy (IT) for seasonal allergic rhinitis. This study included 51 patients with seasonal allergic rhinitis due to the pollen and 8 nonatopic healthy volunteers (nonatopic group). Thirty-nine patients had been undergoing IT using the pollen extracts for various lengths of time (IT group). The remaining 12 patients had never been treated with IT (untreated group). Peripheral blood mononuclear cells (3.3 x 10(6) cells per milliliter) from each individual were cultured with Cry j 1, 4.17 microg/mL. After 96 hours, culture supernatants were harvested to determine the concentrations of IgE, interleukin (IL) 5, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). The levels of IgE (P = .02), IL-5 (P<.01), and TNF-alpha (P = .05) were significantly higher in the untreated group than in the nonatopic group. The levels of IFN-gamma did not differ significantly between the untreated and the nonatopic groups (P = .19). The levels of IgE, IL-5, and IFN-gamma, but not of TNF-alpha, were inversely correlated with the duration (in years) of IT, and none of the levels of IgE (P = .74), IL-5 (P = .15), IFN-gamma (P = .61), and TNF-alpha (P = .55) differed significantly between the nonatopic group and those who had been treated with IT for 10 years or more. The levels of IL-5 were significantly lower in the good responders than in the poor responders to IT (P<.001), whereas the levels of total IgE (P = .20), IFN-gamma (P = .16), and TNF-alpha (P = .14) did not differ significantly between them. The mechanisms responsible for the clinical efficacy of pollen IT are principally related to the tolerance or anergy of T helper 2 cells.

A multi‐centre randomized trial of two different doses of nicotinamide in patients with recent‐onset Type 1 diabetes (the IMDIAB VI)

Background Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta-analysis of the use of NA in patients with recent-onset Type 1 diabetes. Methods In this study we compared two different doses of NA in 74 patients with duration of Type 1 diabetes <4 weeks (mean age 13 years). Patients were randomly allocated in blind to two treatment groups: 38 patients received a dose of 25 mg/kg (b.w.) of NA and 36 patients received a dose of 50 mg/kg (b.w.) of NA. Intensive insulin therapy was carried out in order to optimize metabolic control as soon as possible after diagnosis and to maintain blood glucose level as near to normal as possible. Response to therapy was monitored throughout the study by investigating the occurrence of clinical (complete) remission defined, according to the recommendations of the International Diabetes Immunotherapy Group, as restoration of normal fasting and post-prandial blood glucose without any insulin administration for more than 2 weeks. Moreover, the integrated measures of metabolic control (C-peptide, HbA1c and insulin dose) were analysed at 3- month intervals up to 1 year after diagnosis. Results There were no significant differences in the integrated measures of metabolic control between the two NA treated groups either at onset of the disease or at each 3-month interval up to 1 year after diagnosis, although there was a tendency toward higher insulin dosages in the 50 mg NA group. No significant differences were observed in the rate of clinical remission between the two groups. Conclusion We conclude that patients with recent-onset Type 1 diabetes treated with two different doses of NA, in addition to intensive insulin therapy, show similar residual beta-cell function 1 year later. Since both doses of NA are likely to be effective in reducing beta-cell dysfunction, the smaller dose of 25 mg/kg NA would be sufficient as a higher dose may induce insulin resistance. Copyright © 1999 John Wiley & Sons, Ltd.

Immunotherapy in children with allergic asthma: Effect on bronchial hyperreactivity and pharmacotherapy

Background: 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. Subjects: 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. Methods: 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. Results: PC 20 allergen increased significantly in both the active immunotherapy group ( P < .001) and in the placebo-pollen group ( P < .05). PC 20 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 PC 20 allergen ( P = .001) but not for PC 20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. Conclusion: 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. (J Allergy Clin Immunol 1999;103:609-14.)

Decrease of serum levels of soluble CD23 during immunotherapy in patients with perennial allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating the synthesis of human IgE and is likely involved in the expression of allergic diseases. Our study has aimed at investigating whether serum sCD23 is elevated in patients with perennial allergic rhinitis as compared to nonatopic controls, whether sCD23 in perennial allergic rhinitis fluctuates during the natural course in untreated patients, and whether sCD23 is decreased by immunotherapy. This study included 139 patients with perennial allergic rhinitis due to Dermatophagoides farinae who gave informed consent to participation. They were divided into 2 groups--an untreated group and an immunotherapy group--according to their treatment background. Thirty-one nonallergic, healthy volunteers were included to serve as controls. Symptom scores and serum concentrations of IgE specific to D. farinae and sCD23 were examined twice in each patient: at enrollment (first evaluation) and on a variant time course after enrollment (second evaluation). Serum concentrations of sCD23 were measured by a sandwich enzyme-linked immunosorbent assay. The level of sCD23 in patients with perennial allergic rhinitis was significantly higher than that in nonatopic controls (p < .0001). The level of sCD23 in perennial allergic rhinitis was correlated with the level of specific IgE against D. farinae. The sCD23 level did not fluctuate during the natural course for a span of 2.8 +/- 2.7 years in untreated patients (p = .1337), but was significantly decreased in patients who received immunotherapy for 2.7 +/- 2.2 years (p < .0001). The rate of decrease in sCD23 was significantly correlated with the rate of decrease in specific IgE (rs = .523, p < .0001) and symptom scores (rs = .450, p < .0001). In conclusion, the reduction in sCD23 during immunotherapy is probably related to the decrease in specific IgE and also plays a role in mediating its clinical effect.

The effect of short-term immunotherapy with molecular standardized grass and rye allergens on eosinophil cationic protein and tryptase in nasal secretions

Background: Activation of mast cells and eosinophils under pollen exposure can be inhibited by specific immunotherapy. Objective: The effect of short-term immunotherapy with 7 preseasonal injections of molecular standardized allergens from grass and rye pollen on eosinophil cationic protein (ECP) and tryptase levels in nasal secretions has been compared with symptomatic drug treatment in an open, randomized study with 48 patients. Methods: Nasal reactivity and mediator levels in nasal secretions were measured at baseline, before season, in season, and after season. Results: Symptom scores in the immunotherapy group were 134.5 (95% CI, 65 to 336) versus 386.0 (95% CI, 185 to 563), significantly lower as in the drug-treated group. ECP and tryptase levels increased significantly during natural allergen exposition. The seasonal levels in the immunotherapy group were significantly lower than in the drug-treated group with 272.1 ng/mL (252.0 to 293.9 ng/mL; immunotherapy) versus 470.4 ng/mL (SEM, 435.6 to 508.0 ng/mL; drugs) for ECP and with 8.73 ng/mL (SEM, 8.20 to 9.29 ng/mL) versus 17.47 ng/mL (16.42 to 18.60 ng/mL) for tryptase (all, P < .001). The ECP level induced by nasal provocation was 105.6 ng/mL (99.0 to 112.6 ng/mL) versus 180.4 ng/mL (169.2 to 192.4 ng/mL), significantly lower ( P < .001) in the immunotherapy group, as was the tryptase level with 12.12 ng/mL (11.53 to 12.75 ng/mL) versus 8.19 ng/mL (7.79 to 8.62 ng/mL; P < .001) at the after-season visit. Conclusion: Short-term immunotherapy is able to reduce tryptase and ECP in nasal secretions more effectively than drug treatment in patients with allergic rhinitis. (J Allergy Clin Immunol 1999;103:47-53.)

Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating IgE synthesis, but the in vivo physiologic significance remains to be established. This study investigated the seasonal changes in sCD23 in patients with seasonal allergic rhinitis. It included 112 adult patients with seasonal allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy volunteers. The 64 patients of the pharmacotherapy group were treated with nonsedating antihistamine tablets alone throughout the pollen season and the remaining 48 patients of the immunotherapy group continued to be treated with immunotherapy. Serum concentrations of sCD23 were measured in each patient, before and during the pollen season of 1996, by a sandwich enzyme-linked immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group before the pollen season were significantly higher than those in the nonatopic group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal increase in sCD23 was significant in the pharmacotherapy group, irrespective of the clinical response (P < .0001). By contrast, sCD23 was not significantly increased in the good responders to immunotherapy (P = .1826), but was significantly increased in the poor responders to immunotherapy (P = .0052). A significant correlation between seasonal increase in rate in specific IgE and seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P = .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably involved in seasonal rise in specific IgE in patients with seasonal allergic rhinitis, and successful immunotherapy is capable of blunting seasonal increase in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and clinical benefits during the pollen season.