Local Nasal Immunotherapy Research Articles

Local nasal immunotherapy with birch pollen-galactomannan conjugate-containing ointment in mice and humans

BackgroundAllergen immunotherapy (AIT) is the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergy. Owing to the high prevalence and early onset of hay fever and pollen-food allergy syndrome (PFAS), a safer and simpler treatment method than conventional AIT is needed. To develop a local nasal immunotherapy using an ointment containing hypoallergenic pollen and assess its efficacy in mice and healthy humans. MethodsHypoallergenicity was achieved by combining pollen and galactomannan through the Maillard reaction to create birch pollen-galactomannan conjugate (BP-GMC). The binding of galactomannan to Bet v 1 was confirmed using electrophoresis and Western blotting (WB). Binding of specific IgE antibodies to BP-GMC was verified using enzyme-linked immunosorbent assay (ELISA) and basophil activation test (BAT). The localization of BP-GMC absorption was confirmed using a BALB/c mouse model. BP-GMC mixed with white petrolatum was intranasally administered to 10 healthy individuals (active drugs, 8; placebo, 2) for 14 days. ResultsIn electrophoresis and WB, no 17-kDa band was observed. In ELISA and BAT, BP-GMC did not react to specific IgE but was bound to IgA and IgG. In the mouse model, BP-GMC was detected in nasopharyngeal-associated lymphoid tissues. In the active drug group, the salivary-specific IgA level significantly increased on day 15 (p = 0.0299), while the serum-specific IgG level significantly increased on day 85 (p = 0.0006). ConclusionsThe BP-GMC ointment rapidly produced antagonistic antibodies against IgE; it is safe and easy to use and might serve as a therapeutic antigen for hay fever and PFAS.

Evaluation of local nasal immunotherapy to Dermatophagoides sp. in patients with allergic rhinitis

Introduction: The aim of this study was to evaluate the clinical efficacy of allergen-specific nasal immunotherapy (LNIT) by observing the improvement in the patient’s quality of life, and the side effects of this route of immunotherapy. Methods: From a cohort of 2687 patients with perennial rhinitis treated at the Clinical and Experimental Immunology Service-Hospital Geral-Santa Casa da Misericórdia do Rio de Janeiro for 5 years, a total of one hundred thirty six patients positive in the prick test for Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), were divided into two groups of cases (n=108) and controls (n=28) undergoing or not LNIT, both submitted to the same type of control treatment for the same amount of time. Both groups were classified into mild, moderate and severe rhinitis. Quality of life was assessed based on a questionnaire for Rhinoconjunctivitis, carried out at each visit, with a rating from 0 to 6 according to the increasing degree of difficulty in performing common tasks or nasal, ocular or other symptoms. Results: No systemic side effects or bronchospasms were observed in the cases. Both patients and controls with moderate and severe rhinitis had quality of life grades 3 and 4; 5 and 6 respectively, before immunotherapy. Comparison of cases with controls during the controller medication phase associated with nasal immunotherapy (cases) showed an improvement in quality of life for both (Grades: 0-2, after 5 weeks). Full use of the controller medication was 15 weeks followed by more eighteen weeks with half doses. Patients under LNIT, when the control medication was withdrawn after the sixth series of nasal immunotherapy, maintained the improvement in quality of life with grades of 0-1, not requiring regular and frequent use of symptomatic therapy. Until the final evaluation time, three years and two months, the patients who remained until the end of the immunotherapy regimen (n=89) did not present or significantly reduced the need for control medication, remaining with a degree of quality of life: Degree: 0 and 1.The controls, in the period of 33 weeks of return for consultations, with the withdrawal of the controller medication, reported that they needed the frequent use of controller medicines due to the recurrence of symptoms. The quality of life questionnaire showed a worsening, with grades ranging from 3 to 5, when evaluated in this phase without regular symptomatic medication. Conclusions: The of LNIT performed with full concentrations, did not show secondary reactions with risks to patients and that the effect of inducing tolerance to the antigens of Dermatophagoides sp. was achieved, based on the observation of the decrease in the use of control medications for signs and symptoms and mainly by the improvement in the patients’ quality of life.

Specific local nasal immunotherapy: Single center experience on 324 patients

ObjectiveTo evaluate the efficacy and safety of specific local nasal immunotherapy (LNIT) in patients with allergic rhinitis. Materials and methodsA retrospective single-center study of 324 patients with allergic rhinitis (191 allergic to mites, 133 allergic to Grarninaceae or Parietaria pollen) treated with specific LNIT was carried out. As control group, 158 patients without allergic rhinitis were enrolled. All patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. ResultsClinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test and the rhinomanometric analysis confirm the result with a difference statistically significant. No differnces in mucociliary clearance time were found. ConclusionsSpecific LNIT is a valide alternative to subcutaneous and sublingual administration. It is effective, safe, well tolerated by the patient, it can be done at home with fewer systemic reactions.

LNIT-Local nasal immunotherapy in allergic rhinitis: revisited evidence and perspectives.

Allergen immunotherapy (AIT) is a personalized treatment approach for the allergic airway disease. The most common routes of administration are subcutaneous and sublingual. Local nasal immunotherapy (LNIT) presents another alternative route for allergen desensitization. Nasal mucosa is the first entry site of pathogens and numerous lymphoid organs are located in this area, making LNIT a favorable method for triggering immune tolerance. LNIT has shown promising results in reducing symptoms and medication use in allergic rhinitis patients. Over time, difficulties in dosing adjustments have made this method less popular. Recent advances in intranasal drug delivery systems warrant re-examination of LNIT as a viable option for the treatment of the allergic airway disease. The scope of the review includes evidences of LNIT in human trials including comparison with placebo and conventional method of immunotherapy. Recent articles regarding the mechanism of LNIT and the challenges of intranasal drug delivery are reviewed. Advances in the LNIT delivery system which have overcome previous limitations demonstrate promising effects. LNIT presents a judicious alternative for noninjection AIT. The evidences from previous clinical trials and the novel improvement of drug delivery system will lead into the future allergen vaccine production.

Local nasal immunotherapy for allergic rhinitis: A systematic review and meta-analysis.

Local nasal immunotherapy (LNIT), an alternative noninjection immunotherapy method, is theoretically an efficient method for inducing immunotolerance directly in the affected organ. LNIT is more convenient and less invasive than injection immunotherapy, with fewer systemic reactions. The development of adjuvants to overcome LNIT's limitations raises the possibility of it being an alternative allergen immunotherapy. To evaluate the clinical and immunological efficacy and safety of LNIT for patients with allergic rhinitis. A systematic search for randomized controlled trials comparing LNIT and placebo was performed using OVID Medline and Embase. Outcomes were total nasal symptom score (TNSS), symptom-medication score (SMS), medication score, immunological assessment, and nasal provocation threshold. Data were pooled for meta-analysis. A total of 20 studies with 698 participants were included. The LNIT group had greater posttreatment improvement in TNSS, SMS, and medication score than control (TNSS: standardized mean difference [SMD], -1.37 [95% confidence interval [CI], -2.04 to -0.69]; SMS: SMD, -1.55 [95% CI, -2.83 to -0.28]; and medication score: SMD, -1.09 [95% CI, -1.35 to -0.83]). Immunological assessments showed no significant differences in serum-specific IgE (mean difference [MD], 6.35; 95% CI, -4.62 to 17.31), nasal IgE (MD, -0.59; 95% CI, -1.99 to 0.81), or nasal eosinophil cationic protein (MD, 7.63; 95% CI, -18.65 to 33.91). Only serum IgG significantly increased with LNIT (MD, 0.45; 95% CI, 0.20, 0.70). Posttreatment, nasal provocation threshold was higher with LNIT (MD, 27.30; 95% CI, 10.13-44.46). No significant adverse events were reported. LNIT is a safe alternative allergen immunotherapy route without significant adverse events. It improves clinical symptoms, reduces medication usage, and increases the nasal provocation threshold.

Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation.

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4+ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4+/CD4+ T cells could be downregulated and the IFN-γ+/CD4+ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4+CD25+ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.

Diverse Mechanisms of Allergen Specific Immunotherapy

Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

New routes of allergen immunotherapy.

Allergen immunotherapy is the only cure for immunoglobulin E mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common treatments. In this article, we reviewed new routes of allergen immunotherapy. Data on alternative routes to allow intralymphatic immunotherapy (ILIT), epicutaneous immunotherapy (EPIT), local nasal immunotherapy (LNIT), oral immunotherapy (OIT), and oral mucosal immunotherapy (OMIT) were gathered from the literature and were discussed. ILIT features direct injection of allergens into lymph nodes. ILIT may be clinically effective after only a few injections and induces allergen-specific immunoglobulin G, similarly to SCIT. A limitation of ILIT is that intralymphatic injections are required. EPIT features allergen administration by using patches mounted on the skin. EPIT seeks to target epidermal antigen-presenting Langerhans cells rather than mast cells or the vasculature; this should reduce both local and systemic adverse effects. LNIT involves the spraying of allergen extracts into the nasal cavity. Natural or chemically modified allergens (the latter, termed allergoids, lack immunoglobulin E reactivity) are prepared in a soluble form. OIT involves the regular administration of small amounts of a food allergen by mouth and commences with low oral doses, which are then increased as tolerance develops. OMIT seeks to deliver allergenic proteins to an expanded population of Langerhans cells in the mucosa of the oral cavity. ILIT, EPIT, LNIT, OIT, and OMIT are new routes for allergen immunotherapy. They are safe and effective.

Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denatured Dermatophagoides pteronyssinus

Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunotherapy (LNIT) with urea-denatured Der p crude extract (DN-Dp) significantly decreased compared to that in the normal saline (NS) treatment group. Expressions of IL-4 were significantly reduced in lung tissues after treatment. Inflammation around the bronchial epithelium improved and airway hypersensitivity was down-regulated. LNIT with DN-Dp can down-regulate IL-1b, IL-6 and TNF-a expression and then decrease Der p-induced allergic airway inflammation. This therapeutic modality may be used as an alternative treatment for airway allergic diseases.

Local nasal immunotherapy for allergic rhinitis

Reason for Withdrawal Withdrawn from The Cochrane Library from Issue 3, 2015. Review could not be completed. To view the published versions of this article, please click the 'Other versions' tab.

Clinical Effectiveness of Tyrophagus putrescentiae Allergy by Local Nasal Immunotherapy Using Strips of Dermatophagoides pteronyssinus

Background. House dust mites are a major source of aeroallergens for patients with allergic rhinitis and asthma. Most patients with allergic rhinitis are simultaneously sensitized by Dermatophagoides pteronyssinus (Dp) and Tyrophagus putrescentiae (Tp). Dp and Tp allergy in allergic rhinitis can be caused by cross-reactivity, and the group 2 mite allergens appear to be the major cross-reactive allergens in mites. We previously demonstrated that local nasal immunotherapy (LNIT) with Dp-coated strips could modulate the serum levels of Dp-specific IgE. The aim of this study was to investigate whether Tp allergy could be modulated by LNIT with Dp. Methods. Both Tyr p2-specific IgE in the sera and its effect on Tyr p2-triggered basophil histamine release (BHR) were measured to evaluate the Tp-mediated allergic reaction before and after LNIT. Results. The results showed that not only was Tyr p2-specific IgE reduced, but also Tyr p2-triggered histamine release in the sera after LNIT with Dp allergen strips. There was a significant reduction of Tyr p2-specific IgG1 and upregulation of IgG4 after LNIT with Dp allergen strips. When the amounts of histamine were compared between the two groups, rDer p2-triggering or rTyr p2-triggering histamine release was significantly reduced in the Dp treatment group compared with the normal saline treatment group. No matter in the rDer p2-triggering or rTyr p2-triggering histamine release, differences between before LNIT and after LNIT were statistically significant in the Dp group. Conclusion. Our study demonstrated that not only was Tyr p2-specific IgE reduced in the sera, but also its biological activity of Tyr p2-triggered BHR after LNIT with Dp strips. It is conceivable that the clinical effectiveness of Tp allergy by LNIT with Dp allergen strips may exist.

Local Nasal Immunotherapy: Efficacy of Dermatophagoides farinae-Chitosan Vaccine in Murine Asthma

Background: Local nasal immunotherapy has been reported to be effective for airway allergic diseases. A biodegradable material, chitosan (CS), has been reported to be safe and effective in allergen delivery.In this study, we tested immunotherapeutic efficiency by intranasal administration of Der f entrapped in CS microparticles to sensitized mice. Methods: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by intranasal treatment with PBS, CS, Der f or Der f-CS nano-vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week, and we analyzed their clinical symptoms, antibody expression levels, cytokine levels, T cell proliferation and regulatory T cell numbers. Results: Mice treated with intranasal Der f-CS nano-vaccine prior to challenge displayed an alleviated spectrum of symptoms including airway hyper-reactivity, lung inflammation and mucus production and had fewer eosinophilic cells in bronchoalveolar lavage fluid (BALF). Interestingly, the cytokine levels in Der f-specific IgE were reduced, but IgA in serum and BALF was increased. We also observed that IL-4 was reduced and IFN-γ and IL-10 were increased among splenocytes and in BALF, which inhibits Der f-specific T-cell proliferation in splenocytes and increases regulatory T cells in the spleen. However, the mice challenged without intranasal Der f or Der f-CS vaccine treatment developed allergic asthma. Conclusion: Our results illustrate that intranasal administration of Der f-CS nano-vaccine plays roles in immunologic protection in murine allergic asthma by inducing regulatory T cells and Th1-type reaction.

The Effect of Local Nasal Immunotherapy in Allergic Rhinitis: Using Strips of the Allergen Dermatophagoides pteronyssinus

Local nasal immunotherapy (LNIT) has been reported to be effective for mite-induced allergic rhinitis. However, its compliance is poor due to persistent nasal reactions and difficult application. The main objective of this study was to develop a Dermatophagoides pteronyssinus (Der p)-coated strip for self-application and to evaluate its clinical efficacy. Randomized, double-blind, placebo-controlled trials were carried out to evaluate the efficacy and compliance of LNIT. A total of 35 patients with allergic rhinitis from the allergy clinic were recruited to receive four months of LNIT. Clinical efficacy was evaluated by the symptoms of sneezing, rhinorrhea and nasal stuffiness. Local and systemic effects were evaluated by measuring histamine and eosinophil cationic protein (ECP) in nasal discharge and allergen-specific IgG1, IgG4 and IgE in sera. LNIT with Der p-coated strips could reduce nasal symptoms and modulate the serum levels of Der p-specific IgG1, IgG4 and IgE. The secretion of both histamine and ECP was reduced within four months after treatment. When the symptomatic and immunological changes were compared between active treatment and placebo groups, the improvements were greater in the active treatment groups for all three symptom scores. There were no severe adverse events except nasal response persisting within the first month in some cases. LNIT with a steady dose of Der p-coated strips can be self-administered at home without any systemic reactions. Both local and systemic immune responses were observed after LNIT. This therapeutic modality may serve as a good alternative treatment for allergic rhinitis.

Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis. Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the pollen extract was intranasally administered 6 times a week until the 30th challenge. Sneezing frequency was counted after each of the challenges. As an indicator of nasal blockage, changes in specific airway resistance were measured. Nasal hyperresponsiveness was assessed by measuring leukotriene D(4)-induced nasal blockage. Additionally, during the immunotherapy, we applied pollen onto the ocular surface to induce the allergic conjunctivitis symptoms. At the 11th-30th challenges, the nasal immunotherapy showed inhibition or a tendency to inhibit the biphasic nasal blockage although the inhibitions were variable at respective challenges. The development of nasal hyperresponsiveness was markedly suppressed by the immunotherapy. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. On the other hand, the nasal immunotherapy did not affect the induction of allergic conjunctivitis symptoms. Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

Local nasal immunotherapy in allergic rhinitis

Local nasal immunotherapy in allergic rhinitis

Local nasal specific immunotherapy for allergic rhinitis.

The possibility of producing local hyposensitization by administering allergens via mucosal routes was envisaged at the beginning of 1900, and local nasal immunotherapy has been extensively studied since the 1970s. Presently, there are 21 randomized controlled trials being conducted with the most common allergens, consistently showing the clinical efficacy of local nasal immunotherapy for rhinitis. Other advantages are that it has an optimal safety profile and can be self-administered at home by the patient. Moreover, there are several data from animal models and from humans that confirm the immunomodulatory effect of intranasally administered antigens. On the other hand, local nasal immunotherapy seems to be effective only on rhinitis symptoms and requires a particular technique of administration. For these reasons, its clinical use is progressively declining in favour of the sublingual route although nasal immunotherapy is validated in official documents and remains a viable alternative to injection.

Production of Salivary Immunoglobulin A and Suppression of Dermatophagoides pteronyssinus-Induced Airway Inflammation by Local Nasal Immunotherapy

Background: Local nasal immunotherapy (LNIT) is an effective immunotherapeutic modality, especially when targeting a single immunodominant peptide from an allergen. However, the working mechanisms of LNIT are poorly understood. We hypothesized that LNIT with a mixture of group 2 allergens of Dermatophagoides pteronyssinus (Der p 2) protein and fungal immunomodulatory peptide (FIP) would generate suppression of Der p-induced airway inflammation through immunoglobulin (Ig) A secretion in the airways. Method: Mice were sensitized with recombinant Der p 2 (rDer p 2) and Der p followed by LNIT with rDer p 2 in conjunction with FIP. After intratracheal challenge with rDer p 2 and Der p, the airway inflammation was determined by analyzing the cell subpopulation and cytokine concentration in the bronchoalveolar lavage fluid. The allergen-specific IgE, IgG2a and IgG in the sera and IgA in the saliva were measured by ELISA. Results: LNIT with rDer p 2 in conjunction with FIP could downregulate the lymphocyte infiltration in both rDer p 2- and Der p-induced airway inflammation. Both total and specific IgA in the saliva were increased after LNIT. Serum levels of IL-4, IL-10 and specific IgE were reduced and the specific IgG2a and IgG increased after LNIT. After LNIT, there was a reduction of airway hypersensitivity at 30 min after allergen challenge in the rDer p 2-and Der p-sensitized mice, with a significant decrease only in rDer p 2-sensitized mice. Conclusion: LNIT with rDer p 2 in conjunction with FIP was not only able to suppress rDer p 2-induced airway inflammation but also generate suppression of Der p-induced airway inflammation. The simultaneous reduction of IL-4 and IL-10 indicated that IL-10-producing cells were not activated by LNIT. The increment of IgA in the airway might play a role in the prevention of airway inflammation.

Pharmacokinetics of radiolabelled Par j 1 administered intranasally to allergic and healthy subjects

Local nasal immunotherapy is accepted as an alternative to the injection route for allergic rhinitis. Despite this, little is known about the kinetics of the allergen after nasal delivery in allergic subjects. We aimed at assessing the biodistribution of 123I-radiolabelled Par j 1 in Parietaria-allergic subjects, in comparison with healthy volunteers. Purified Par j 1 was radiolabelled with 123I and sprayed into the nostrils of three control subjects and three Parietaria-allergic volunteers. Dynamic and static scintigraphic images of the head were recorded at serial times and blood samples were obtained to measure the plasma radioactivity, and to assess the presence of circulating radiolabelled species by gel chromatography. In Parietaria-sensitized subjects, the radiolabelled allergen was rapidly cleared from the nasal cavity and transported to pharynx, and little local persistence was seen. This differed from healthy subjects where nasal clearance of the tracer was slower and nasal radioactivity persisted up to 24 h. The increase in plasma radioactivity paralleled swallowing of the allergen in both groups, and plasma chromatographic profile did not differ between allergic and healthy volunteers. Sensitization to the allergen affects its local biodistribution. Gastrointestinal absorption is relevant also for the intranasal route.

Pharmacokinetics of radiolabelled PAR j 1 administered intranasally to allergic and healthy subjects

Background Local nasal immunotherapy is accepted as an alternative to the injection route for allergic rhinitis. Despite this, little is known about the kinetics of the allergen after nasal delivery in allergic subjects. Objective We aimed at assessing the biodistribution of 1231-radiolabelled Par j 1 in Purietaria-allergic subjects, in comparison with healthy volunteers. Methods Purified Par j 1 was radiolabelled with 123 I and sprayed into the nostrils of three control subjects and three Parietaria-allergie volunteers. Dynamic and static scintigraphic images of the head were recorded at serial times and blood samples were obtained to measure the plasma radioactivity, and to assess the presence of circulating radiolabelled species by gel chromatography. Results In Parietaria -sensitized subjects, the radiolabelled allergen was rapidly cleared from the nasal cavity and transported to pharynx, and little local persistence was seen. This differed from healthy subjects where nasal clearance of the tracer was slower and nasal radioactivity persisted up to 24 h. The increase in plasma radioactivity paralleled swallowing of the allergen in both groups, and plasma chromatographic profile did not differ between allergic and healthy volunteers. Conclusions Sensitization to the allergen affects its local biodistribution. Gastrointestinal absorption is relevant also for the intranasal route.

Sublingual immunotherapy: what lessons can we draw from recent studies?

Allergen-specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened by the risk of severe adverse events; therefore, safer routes of administration (e.g. local routes) have been developed and are being investigated. Controlled clinical trials have failed to demonstrate the clinical efficacy and the safety of oral or bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it could be considered to be a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore, its use is slowly declining. In contrast, the efficacy of sublingual administration in the treatment of asthma and rhinitis in adults and children is supported by numerous controlled trials. The safety profile, assessed in clinical trials and post-marketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper adjustment of the dose. The World Health Organization now considers sublingual immunotherapy as a valid alternative to the subcutaneous route, including its use in children. The long-lasting efficacy of treatment via the sublingual route has been documented recently but a number of points still need to be investigated, including mechanisms of action, optimal dosage, cost-effectiveness and patient's adherence.