Are basophil activation and sulphidoleukotriene determination useful tests for monitoring patients with peach allergy receiving sublingual immunotherapy with a Pru p 3-enriched peach extract?

INTRODUCTION: Treatment of food allergy essentially consists of food avoidance, but immunotherapy with food is emerging as a new therapeutic option. OBJECTIVE: To evaluate clinical improvement and immunological changes in patients with peach allergy following sublingual immunotherapy (SLIT) with a Prup3 quantified peach extract. METHODS: A randomized, double-blind, placebo-controlled clinical trial with peach SLIT was conducted. We assessed clinical efficacy after 6 months of treatment by means of double-blind, placebo-controlled oral challenges with peach and also evaluated immunological changes (basophil activation test [BAT] and determination of sulphidoleukotriene production) following stimulation with peach peel and pulp, rPrup3, rMald 1, and rMal d 4 stimulation. We also measured specific IgE and IgG4 to Pru p3. RESULTS: After 6 months of SLIT (T6), the active group showed a 3-fold improvement in tolerance to Prup3 and a significant increase in IgE to rPrup3 and in sLT production following stimulation with peach peel and rPrup3. There was also a significant increase in BAT results after stimulation with rPrup3 at 1 month of SLIT (T1). Statistically significant between-group differences were only observed for BAT with peach peel and pulp at T1 and T6 and for BAT with rPru p3 at T6. No changes were observed in BAT with rMal d 1 or rMal d 4 or in IgG4 levels to nPrup3. CONCLUSIONS: SLIT with a Pru p 3 quantified peach extract is clinically effective and leads to an increase in basophil activation and sulphidoleukotriene production following stimulation with rPru p3 and peach peel in the first months of treatment.

Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen.

BACKGROUND: Peach allergy is prevalent, persistent, and potentially severe and as such is a target for immunotherapy. Our aims were to evaluate the profile of sensitization to Rosaceae allergens and the effects of sublingual peach immunotherapy on immunoglobulin (Ig) E levels to these allergens, to monitor for neosensitizations, and to check if this treatment modified other Rosaceae fruit and pollen-related sensitizations. METHODS: A double-blind placebo-controlled trial was conducted on 56 peach-allergic patients who received, sublingually, a standardized peach extract quantified in mass units of Pru p 3, or placebo for 6 months. IgE to recombinant (r) Mal d 1, rMal d 4, rPru p 3, and natural (n) Art v 3 and skin prick test (SPT) reactivity to Platanus pollen and apple extracts evaluated before treatment (T0), after 1 month (T1) and after and 6 months (T6) were recorded. RESULTS: In total, 18.5% of patients recognized rMal d 1, 83.3%, rPru p 3, 24.1%, rMal d 4, and 25.9% nArt v 3. IgE to Pru p 3 rose from T0 to T1 in both the active group (P = .003) and the placebo group (P = .022), and remained elevated at T6 in the active group (P = .001). IgE to other purified allergens did not change significantly and no relevant neosensitizations were detected. SPT reactions to peach decreased from T0 to T6 in the active group (P < 0.05). Reactivity to peach (T1 and T6) and apple (T6) was lower in the active group than in the control group. CONCLUSIONS: The main allergen was Pru p 3. Changes in rPru p 3 IgE levels and in peach and apple extract SPT were induced by sublingual immunotherapy.

Once daily sublingual immunotherapy without updosing--A new treatment schedule.

BACKGROUND: Treatment regimens with specific immunotherapy include updosing. Due to excellent tolerance of sublingual immunotherapy (SLIT), it was hypothesized that administration of once-daily SLIT could be initiated safely without updosing. The objective was to evaluate tolerability of SLIT administered once daily without updosing. METHODS: 135 patients suffering from allergic rhinitis with/without asthma were included in a double-blind, placebo-controlled, parallel-group study. Patients were randomized into two groups. Group 1 (n = 69) received active treatment throughout the study, including 10 days updosing (T1), 20 days maintenance treatment (T2), and 2 consecutive months on maintenance treatment (T3 and T4). Group 2 (n = 66) obtained placebo updosing (T1), placebo maintenance (T2), initiated active treatment (maintenance) at T3, and continued active treatment until the end of the study (T4). Adverse events (AEs) were assessed at T1-T4. 66 grass- and 69 mite-allergic patients were evenly distributed between groups. RESULTS: 229 AEs were reported, 157 AEs were related to treatment. The most frequently reported AEs (>5% of patients in any group) related to treatment were oral itching, ocular itching, rhinitis, and sublingual edema. For group 1 at T2, the rate of all AEs related to treatment per dose administered was 1.79%, and for group 2 at T3 the rate was 1.33% (p = 0.37). For the most frequently reported AE, oral itching, the rate per dose administered was 1.01% for group 1 at T2, and 0.74% for group 2 at T3 (p = 0.53). CONCLUSIONS: Once daily SLIT was well tolerated and can be safely initiated without updosing.

Biological standardization and maximum tolerated dose estimation of an Alternaria alternata allergenic extract.

BACKGROUND: The manufacture of allergenic extracts from the mold Alternaria alternata is influenced by factors such as strain variability, allergenic origin, culturing conditions and extraction process, which affect the reproducibility of the preparations intended for diagnostic and therapeutic use. OBJECTIVES: To select the most adequate antigenic source of A. alternata extracts and determine its maximum tolerated dose (MTD) to be used in a subsequent immunotherapy efficacy clinical trial. METHODS: Twenty-one patients monosensitized to A. alternata were involved in a biological standardization process of A. alternata extracts. Four different mold strains were cultured and used to produce extracts by three different methods, each incorporating proteins from different origins: culture filtrate, buffer extractable fraction and cellular antigens. The selected extract, characterized as in-house reference (IHR) preparation was used in a MTD finding immunotherapy study. Serum IgE, IgG, IgG1 and IgG4 specific of complete extract and purified natural and recombinant forms of Alt a 1 were determined by different EIA methods. RESULTS: Culture filtrate extract containing the allergens secreted to the spent medium was shown to be the most adequate option for establishing an IHR preparation for A. alternata extract manufacturing. A maximum dose of 1670 UBE, equivalent to 0.1 microg Alt a 1, was determined as MTD for immunotherapy. One year of administration of such a dose at monthly intervals elicited pronounced immunological changes with statistically significant decreases in IgE and increases in IgG4, both estimated with whole extract or purified Alt a 1. CONCLUSION: A high quality natural A. alternata extract has been developed and preliminarily tested to define its MTD for subsequent determination of the optimal dose in an immunotherapy efficacy clinical trial.

[Treatment of allergy to mushrooms]. / Tratamiento de la alergia a hongos.

The treatment of patients with respiratory allergy is based on environmental control measures, pharmacological and immunotherapy treatment. The third cause of allergic respiratory disease in our environment is mushrooms, the most frequently involved being the Alternaria class. However, due to the great difficulties in their diagnosis and specific treatment, there are few controlled studies on immunotherapy with mushroom extracts. A clinical test was carried out with a suitable, biologically standardized extract for the diagnosis and treatment of patients allergic to Alternaria. A second phase determined the maximum tolerated dosage of this extract administered through immunotherapy, in depot preparation and in conventional dosage, which was 0.1 mg/ml of Alt a I. This dosage was established as the maintenance dosage in the following phase (double blind test controlled with placebo), in which the efficacy and safety of the immunotherapy with this extract was determined, administered in immunotherapy to the mentioned maintenance dosage, to 28 patients with rhinitis and/or asthma due to allergy to Alternaria. All the patients reached the pre-established maintenance dosage of 1670 BSU. The treatment proved efficient, producing an improvement in the symptoms, respiratory function, subjective evaluation of patient and doctor, and severity of the disease. The immunological response supported the clinical efficacy, with an increase in the IgG and a fall in the IgE over the course of the study. Tolerance to the treatment was excellent, with only two light systemic reactions registered in the 711 dosages administered (0.28% reactions/dosages administered).

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

A prospective safety-monitoring study of immunotherapy with biologically standardized extracts.

We evaluated the safety of immunotherapy in 419 patients who attended our allergy department for treatment. They were suffering from rhinitis and asthma caused by sensitization to grass pollen or Dermatophagoides pteronyssinus. Immunotherapy was given by biologically standardized aluminum hydroxide adsorbed extracts according to a conventional schedule. Local reactions were recorded in 10.5% of the patients and systemic reactions in 4.8%. Only 0.37% of the doses administered were associated with systemic side-effects. We found that 84% of the patients who showed systemic reactions were asthmatic subjects (P < 0.01), and most of them were sensitized to D. pteronyssinus (71%). Side-effects occurred more frequently during the dose-increase period (P < 0.05). After 9482 doses had been administered, no anaphylactic shock or life-threatening reactions were registered. We believe the risk associated with immunotherapy to be drastically reduced when treatment is carefully monitored by skilled personnel. In such conditions, as shown by our study, immunotherapy is safe.