Olea sublingual allergoid immunotherapy administered with two different treatment regimens.

Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid administered in accordance with the standard regimen has proven to be effective and safe. Achieving clinical benefit, however, requires a lengthy period of time so it is not very suitable for short-lasting allergies. We thus performed this study to compare an administration protocol starting in the coseasonal period (with a 4-day build-up phase) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time. The prospective, randomized, drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma. Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks, 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks, and 12 to drug therapy. They were treated from April or May to June 2008. A visual analog scale (VAS) was performed at baseline and after treatment to assess the well being of the patients. Drug consumption was evaluated by means of a monthly diary. There was greater VAS improvement in both the SLIT groups versus the controls, but it was statistically significant only in the coseasonal group (p < 0.01). Furthermore, there was a reduction in the rescue medication only in the coseasonal SLIT (p < 0.05 versus drug therapy). One mild adverse event was observed. The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used.

Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production.

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and efficacious in the treatment of patients with allergic rhinitis. Although favorable clinical effects have been observed with controlled trials as early as a few months since the beginning of treatment, few biological changes induced by SLIT have been demonstrated. OBJECTIVE: To investigate in grass-allergic patients the effect of a 2-month SLIT regimen, administered with a simplified protocol without up-dosing, on proliferation and production of cytokines characteristic of the regulatory T-cell phenotype (interleukin 10 [IL-10] and transforming growth factor beta [TGF-beta]) by allergen-specific T cells. METHODS: Patients were recruited to the study in January 2006. SLIT was performed by self-administration and was continued for 60 days from February to April 2006. Eleven grass pollen-allergic patients with seasonal rhinitis were treated daily before the pollen season for 2 months with a modified allergen (monomeric allergoid) derived from a 3-grass pollen extract. Allergen-specific proliferation and production of IL-10 and TGF-beta were measured on peripheral blood mononuclear cells at baseline and treatment end. Tetanus toxoid served as the control antigen. RESULTS: After SLIT, allergen-specific (P = .002) but not tetanus toxoid-specific proliferation decreased, whereas IL-10 transcription increased (P < .001). TGB-beta transcription was also increased after treatment, although not statistically significantly (P = .06). Changes in proliferation to allergen and in IL-10 transcription were correlated (r = -0.82, P = .003). CONCLUSIONS: A short-term course of SLIT with modified allergen in grass-allergic patients is associated with the reduction of allergen-specific proliferation and with the up-regulation of the IL-10 regulatory cytokine.

Long-lasting effects of sublingual immunotherapy for house dust mites in allergic rhinitis with bronchial hyperreactivity: A long-term (13-year) retrospective study in real life.

BACKGROUND: Subcutaneous immunotherapy for respiratory allergy has shown a long lasting efficacy after its discontinuation, whereas evidence in the case of sublingual immunotherapy (SLIT) is weak. This retrospective study evaluates whether SLIT exerts a long-lasting effect and whether it relates to its duration. METHODS: Sixty-five patients allergic to mite and positive to methacholine challenge 13 years ago were studied. Twelve (control group, SLIT 0) were treated for 4 years only with standard pharmacological therapy (SPT), while 53 received SLIT and SPT. Among these, four groups were identified according to SLIT duration. Fifteen patients were treated for 1 year (SLIT 1), 10 for 2 (SLIT 2), 14 for 3 (SLIT 3) and 14 for 4 years (SLIT 4). Clinical parameters (symptom monthly score, SMS), bronchial reactivity and FEV1 were evaluated in 1992 (run-in), 1993 (baseline) and every 2 years from 1997 to 2005. RESULTS: Two to 3 years after the treatment ended, a positive effect on SMS, but not methacholine challenge and FEV1, was seen in the SLIT groups versus SLIT 0. At this time interval an effect on methacholine challenge was also seen in SLIT 3. After 7-8 years a significant difference was seen for SMS, i.e., it was significantly better in SLIT 4 than in the other groups, while bronchial reactivity was still improved in SLIT 1, 3 and 4 only after 5-6 years. CONCLUSIONS: The effects of a 4-year SLIT on clinical parameters but not bronchial reactivity and FEV1 last 7-8 years after its discontinuation. SLIT shorter than 4 years yields proportionally less impressive results.

Pharmacokinetics of Der p 2 allergen and derived monomeric allergoid in allergic volunteers.

BACKGROUND: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers. METHODS: Purified Der p 2 and its monomeric allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography. RESULTS: The local pharmacokinetics did not differ between allergen and allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1-2 h. Both the allergen and the allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the allergoid, but not the allergen, was absorbed as an intact molecule. CONCLUSIONS: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the allergoid in the mechanism of action of sublingual immunotherapy remains to be defined.

The allergic march in pollinosis: natural history and therapeutic implications.

BACKGROUND: That specific immunotherapy (SIT) can slow the march of allergy has been confirmed in controlled clinical trials. However, an assessment of its effects in everyday life, in a large cohort of patients, might provide further useful information. METHODS: This observational study comprised 3,643 patients allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and intermittent or mild-persistent bronchial asthma, responding poorly to standard pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n = 730). Symptom/drug scores were recorded, respiratory function and skin tests were done, and methacholine challenge was scheduled at the beginning and end of the study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were asked to 'self-medicate' as needed, serving as a control group to check the incidence of asthma. RESULTS: The incidence of rhinitis-asthma co-morbidity was highest in the self-medication group (50.8%). Persistent rhinitis was associated with asthma more often than the intermittent form, regardless of the severity of the symptoms that led to progression to asthma in patients with intermittent rhinitis. Treatment with SIT combined with SPT always slowed the allergic march which, however, was not influenced by drugs alone. CONCLUSIONS: In routine clinical practice, SIT is effective in preventing the allergic march. Patients with persistent rhinitis, who are at greatest risk of progression to asthma, appear to be the most logical candidates.

Allergen biodistribution in humans.

Specific immunotherapy performed by noninjectable (oral, nasal or oromucosal) routes was mostly developed in the last 20 years with the main aim to avoid side effects that occasionally occur in the course of injectable immunotherapy. Although evidence of its clinical efficacy has been provided some pharmacokinetics aspects are still to be elucidated. In this review we discuss experimental findings of mucosal processing, biodistribution in healthy or allergic humans of 123I-labelled major allergen of Parietaria judaica (the most important cause of seasonal allergy in the Mediterranean area) administered by sublingual or nasal routes. The results available to date show that most allergen administered by mucosal route is absorbed via the gastrointestinal tract; however, a proportion is retained at the mucosal level for a relatively long time. These data are potentially useful to improve immunotherapy treatment protocols by noninjectable routes.