Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.     

A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract

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 (Stallergenes) 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.     

Sublingual‐swallow immunotherapy (SLIT) with a standardized five‐grass‐pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy

Background:  The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis.
Methods:  Six hundred and twenty-eight patients with grass pollen rhinoconjunctivitis (≥2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS.
Results:  Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak ( P  = 0.0005 and P  = 0.0014, respectively) and the exploratory combined score ( P  = 0.0001 and P  = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season ( P  < 0.0001) and at the end of the pollen season ( P  = 0.0031 and P  ≤ 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose ( P  < 0.0001).
Conclusions:  All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice.     

Efficacy and safety of specific immunotherapy with a high-dose sublingual grass pollen preparation: a double-blind, placebo-controlled trial.

BACKGROUND: Sublingual immunotherapy (SLIT) is increasingly being used for the treatment of allergic rhinitis, but there are conflicting study results demonstrating clinically relevant efficacy. OBJECTIVE: To show clinical efficacy and safety of a new high-dose grass pollen preparation for SLIT. METHODS: In a 2-year, double-blind, placebo-controlled trial, 185 subjects with rhinitis or rhinoconjunctivitis, with or without asthma, were treated with a recently developed, high-dose, 6-grass pollen mixture for SLIT once daily. RESULTS: The primary end point, a combined symptom-medication score, showed almost no change in the placebo group during a 42-day evaluation period in the grass pollen season from 2003 to 2005, whereas active treatment was associated with a significant and clinically relevant improvement (full analysis set, P = .01; main data set, P = .002). The effect was irrespective of asthma diagnosis. Allergen-specific IgE showed no difference in both groups, and specific IgG4 and IgG1 increased with active treatment in the first and second study years compared with placebo, clearly indicating the immunogenic effect of the active treatment. The SLIT was well tolerated. No serious adverse drug reactions occurred. CONCLUSIONS: High-dose, sublingual, specific immunotherapy with an extract of a 6-grass pollen mixture showed a significant and clinically relevant improvement in subjects with grass pollen-associated rhinitis or rhinoconjunctivitis, with or without asthma. The treatment with the sublingual solution was well tolerated.     

Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma--a placebo controlled study.

BACKGROUND: The efficacy of therapy with sublingual allergen extracts is unproven. OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.     

Immunotherapy with Alpare® in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study

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 Parieiaria. 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.     

Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment

Background The optimal dose (300IR) of a five‐grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. Objective Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. Methods A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double‐blind, placebo‐controlled, multi‐centre, pan‐European trial. Subjects received once‐daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m³ of air, recorded using Hirst‐type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m³. Results The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4±31.1 to 128.6±15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P0.0031) of the pollen season. All doses were well tolerated. Conclusion At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.     

Oralair®: sublingual immunotherapy for the treatment of grass pollen allergic rhinoconjunctivitis

Oralair(?) is a sublingual grass pollen immunotherapy tablet that was authorized for use in Europe on 26 November 2009 and is currently in Phase III clinical trials in the USA. It is indicated for the management of grass pollen allergic rhinitis with or without conjunctivitis in adults, adolescents and children (above the age of 5) with clinically relevant symptoms, confirmed by a positive cutaneous test and/or a positive titer of the specific IgE to the grass pollen. Treatment is composed of an initiation phase (3-day dose escalation: 100 IR [index of reactivity] on day 1, 200 IR on day 2 and 300 IR on day 3) and a continuation phase at a dosage of 300 IR/day. Treatment is scheduled to start approximately 4 months before the actual start of the pollen season and should be continued throughout the season. The treatment should be prescribed and initiated by an experienced allergy specialist.     

The significance of hypersensitivity to nuts in patients with birch pollen allergy

This study was performed in patients with allergic rhinitis/conjunctivitis to birch pollen to determine whether patients with additional hypersensitivity to nuts and apples differed from patients without such hypersensitivity; the determination was in terms of results of skin prick test (SPT), specific IgE antibodies (RAST), and symptoms during the pollen season. Forty-seven patients with birch pollen allergy were investigated by RAST against birch and hazel pollen and by SPT. They were treated in a randomized, double-blind, placebo-controlled study with fluticasone propionate aqueous nasal spray or placebo. The area of the SPTs was larger and the specific IgE values higher in patients with hypersensitivity to nuts and apples. These patients also had more symptoms during the pollen season. We conclude that hypersensitivity to nuts is an indication of a more severe allergy in patients with birch pollen allergic rhinitis.     

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract

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)     

Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives

Background Birch pollen and pollen from related trees of the Fagales order are a major cause of allergic rhinitis, conjunctivitis, and asthma through the spring season in northern and central Europe. Objective To investigate the clinical effects of injection immunotherapy with genetically modified derivatives of major birch pollen allergen Bet v 1 on pollen‐induced allergic symptoms. Methods A three‐arm double‐blind placebo‐controlled immunotherapy study was conducted with one pre‐seasonal course of treatment using two derivatives of Bet v 1, namely a recombinant Bet v 1 trimer and an equimolar mixture of two recombinant Bet v 1 fragments together representing the whole protein sequence. Analysis of local and systemic adverse events was performed for 124 patients who had received at least one dose of medication. Clinical efficacy was monitored by symptom medication scores and interval scoring in the per protocol‐treated population (n=84). In addition, skin and nasal provocation responses and allergen‐specific antibodies were assessed. Results There were trends towards improvement in the subjects' well‐being and clinical symptoms (nasal scores), although comparisons with a placebo group did not show statistical significance in the main end‐point, the combined symptom medication score. Reductions in skin and nasal sensitivity were observed for some subjects with a trend for the Bet v 1 trimer to be more effective than the fragments. Treatment induced strong IgG1 and IgG4 allergen‐specific antibody responses. Local injection‐site reactions were most frequent in the trimer group affecting 59.5% of patients as opposed to 37.8% and 30.6% in the fragment and placebo groups, respectively. Systemic reactions were elicited more frequently by fragments. A large proportion of adverse side‐effects appeared hours following injections, and might be attributable to concurrent exposure to related pollens. Conclusion Single courses of injection immunotherapy with Bet v 1 allergen derivatives showed trends towards improved well‐being and reduced reactivity to specific allergen provocation, but did not yield significant improvement in the combined symptom medication score in this study.     

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

BACKGROUND: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. METHODS: 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. RESULTS: 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. CONCLUSION: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.     

Local nasal immunotherapy for birch allergic rhinitis with extract in powder form

Background Traditional subeutaneous immunotherepy has been proved effective in birch pollenosis. It has, however, some drawbacks as systeic reactions, which are rare but important. Local nasal immunotherapy (LNIT)represents a potential safer route of allergen administration.
Objective To study the clinical efficacy and safety of local nasal immunotherapy by means of an extract in powder form as treatment of birch allergic rhinitis.
Methods Thirty birch allergic patients have been selected on the basis of a positive history, skin test, radioalllergosorbent test assay (RAST)and specific nasal challange. Two 15 patient groups were randomly assigned to the active treatment or to the placebo one. Treatment lasted 22 weeks (14 for the build-up phase and eight for the maintenance period)and symptoms were recorded during the treatment and the birch pollen season.
Results The clinical efficacy of LNIT is suggested by a significant reduction of medication score only in the treated group during the pollen season, although the symptom score was significant increase of specific nasal thereshold dose was obserbved after treatment only in the active treated group. Mild adverse reaction to LNIT, limited to the upper respiratory tract, were reported during the treatment in the active group, but they did not interface with LNIT schedule. No asthmatic or systemic reaction were observed.
Conclusions This Study Indicates that LNIT with allergen in powder form has proven clinically effective in the treatment of birch allergic rhinitis. Further studies are needed to establish weather this treatment can be considered a real alternative to the traditional subeutaneous immunotherapy in birch allergic rhinitis.     

Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): safety and immunologic implications

BACKGROUND: The clinical safety of sublingual immunotherapy (SLIT) has been repeatedly confirmed; nevertheless, the possible onset of local oral symptoms is still a concern, and nothing is known about the pathogenesis of this effect. We aimed to determine whether the administration of SLIT in allergic children can evoke an IgE-mediated reaction, by measuring the levels of sublingual tryptase and ECP. METHODS: Thirty children (7-12 years old) with allergic rhinitis/asthma due to grass pollen were prescribed SLIT. In these children, an allergen-specific nasal challenge was performed, and nasal tryptase and ECP were measured before and after. Sublingual ECP and tryptase were also assessed before the SLIT, after 1 month, and after 6 months of treatment. Ten matched allergic children and 10 healthy ones served as controls for the baseline levels of sublingual ECP and tryptase. RESULTS: The levels of nasal tryptase and ECP significantly increased after nasal challenge (P<0.001), whereas no change during the SLIT course (at the beginning, after 1 month, and after 6 months) could be detected in sublingual tryptase either before or after SLIT administration. The sublingual ECP significantly decreased after 6 months of SLIT. The baseline levels of nasal tryptase and ECP were significantly higher in allergic subjects than in healthy controls, as was the level of sublingual ECP. CONCLUSIONS: In the presence of an IgE-mediated reaction (ASNC), a significant increase of tryptase and ECP can be seen. When SLIT is administered, such a phenomenon does not occur; therefore, SLIT does not elicit any IgE reaction in the mouth. It is noteworthy that allergic subjects display higher levels of nasal ECP and tryptase than healthy subjects, even when symptom-free, and these observations may indicate the presence of subclinical inflammation.     

Use of glutaraldehyde-modified timothy grass pollen extract in nasal hyposensitisation treatment of hay fever.

12 patients suffering from grass pollen hay fever were treated for 14 weeks pre- and co-seasonally by intranasal self-administration of an aqueous solution of a glutaraldehyde-treated timothy grass pollen allergen. These patients had a statistically significant decrease in nasal symptom scores during the grass pollen peak period and in nasal challenge end-point titre after the season compared to placebo-treated patients. No significant effect was seen on the eye symptoms. 1 patient withdrew from the trial as a consequence of too strong local nasal reactions during treatment. Most other patients treated with active material reported mild local reactions during the first minutes after administration of the nasal spray. In the actively treated group a significant increase in serum and nasal secretion of grass pollen specific IgE, IgG and IgA antibodies was obtained during the treatment. In contrast, in the placebo group a significant increase in IgE antibody levels in serum and secretion occurred during the pollen season. The reduction in symptoms and increase in antibody production together with the simplicity of the procedure makes this approach to immunotherapy attractive.     

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway diseases and immunotherapy that appeared during 2006. Studies from Europe continue to examine the usefulness of the Allergic Rhinitis and its Impact on Asthma classification of allergic rhinitis as intermittent or persistent and its levels of severity as mild or moderate/severe. A number of physical agents were shown to effect nasal inflammation: sudden temperature changes in patients with allergic rhinitis increased eosinophilic inflammation; in children with allergic asthma, the personal exposure to particles <2.5 microm air pollution correlated with percent of nasal eosinophils and levels of markers of nasal exudation; and in patients who developed rhinorrhea on exposure to cold and windy weather, nasal challenge with cold dry air caused sloughing of nasal epithelial cells. A 3-month double-blind, placebo-controlled study of nasal washes with amphoteracin B showed no benefit in patients with chronic rhinosinusitis. Studies of immunotherapy with grass and dog dander extracts confirmed the need for doses containing 15 to 20 microg of the major allergen for optimal effectiveness. The protective effect of immunotherapy on the development of asthma in children with allergic rhinitis was shown to still be present 2 years after completion of a 3-year course of treatment. Injection immunotherapy with a moderate dose of house dust mite extract in house dust-sensitive adults with atopic dermatitis reduced symptoms and use of corticosteroids and antihistamines compared with treatment with about 1/1000 of that dose of the same extract. Pretreatment for 9 weeks with the monoclonal anti-IgE antibody omalizumab reduced systemic reactions during rush immunotherapy 5-fold and allowed further build-up at weekly intervals without systemic reactions. A review of sublingual immunotherapy confirmed both efficacy and safety, but evidence for appropriate dosing and for the effectiveness of sublingual immunotherapy employing multiple allergen mixes was still lacking. Two studies with a sublingual grass pollen extract tablet showed a clear dose response and the ability to initiate sublingual immunotherapy without an up-dosing phase. A pilot study with cytosine phosphorothionate quanosine DNA conjugated to the major allergen of ragweed reported impressive improvement in symptoms the first pollen season that persisted during the second pollen season without any further administration of the conjugate. In conclusion, studies on rhinitis and sinusitis explored the pathophysiology of the disease more than offering new therapeutic approaches. Studies on immunotherapy addressed optimal dosing, but also a variety of safer and more convenient approaches such as reduction of IgE with omalizumab, conjugating allergen to immunostimulatory DNA sequences, or administration by the sublingual route.     

Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis

BACKGROUND: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen. METHODS: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch-pollen season, during the grass-pollen season, and after the seasons. Symptom-medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator-independent way. RESULTS: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch-pollen season to the grass-pollen season, followed by a decrease from the grass-pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F-test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine-release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication. CONCLUSIONS: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.     

Safety and efficacy of Juniperus ashei sublingual-swallow ultra-rush pollen immunotherapy in cypress rhinoconjunctivitis. A double-blind, placebo-controlled study

BACKGROUND: The safety and efficacy of high-dose sublingual-swallow immunotherapy (SLIT) has been established in pollen rhinoconjunctivitis. This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica. METHODS: Patients received either placebo or SLIT. Evaluation of safety was based on the frequency of adverse events during the incremental dose period (half a day) and during maintenance therapy (4 months). Evaluation of efficacy was based on symptom and medication scores at the pollen peak. RESULTS: Seventy of the 76 patients included completed the study. There were no drop-outs during the rush procedure. One patient in the active group dropped out during the maintenance therapy due to adverse events: gastric pain and vomiting. There was also 1 drop-out in the placebo group due to pregnancy. Adverse events were infrequent, local and mild. Symptom scores for rhinitis and conjunctivitis were not statistically different between groups, but there was a marked and significant (p < 0.03) decrease of the medication score (about 50%) and nasal steroid consumption (about 75%) in the active treatment group. An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients (p < 0.04 and p < 0.01, respectively). CONCLUSIONS: The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies. SLIT with J. ashei extract, due to its high Jun a 1 content, significantly reduced nasal steroid consumption in patients allergic to European cypress.     

Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers

BACKGROUND: 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. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers. METHODS: 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. RESULTS: 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. CONCLUSION: 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.