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Stephen R Durham - One of the best experts on this subject based on the ideXlab platform.
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grass pollen Immunotherapy for treatment of allergic rhinitis
BMJ, 2014Co-Authors: Anna Slovick, Stephen J Till, Stephen R DurhamAbstract:A 33 year old female teacher presented with a history of troublesome allergic rhinoconjunctivitis and seasonal asthma. Since her teens, from May through to August she had experienced sneezing, nasal congestion, rhinorrhoea, itchy red eyes, and occasional breathlessness. In previous summers, her general practitioner had prescribed daily intranasal budesonide, oral cetirizine, and cromoglicate eye drops, together with inhaled salbutamol as needed. Although she had experienced a modest improvement with this treatment, symptoms continued to impair her concentration in the classroom and her quality of sleep. Her general practitioner referred her for consideration of “desensitisation.” Grass pollen Immunotherapy involves repeated administration of high doses of grass pollen allergen with the aim of inducing clinical and immunological tolerance in the recipient. Immunotherapy formulations contain an extract of one or more species of grass pollen and are administered either as a course of subcutaneous injections (“subcutaneous Immunotherapy”) or as daily sublingual drops or dissolving tablets (“sublingual Immunotherapy”) for three years. Experience with subcutaneous Immunotherapy, first described more than 100 years ago,1 is extensive; experience with sublingual Immunotherapy is less so. In the United Kingdom, grass pollen Immunotherapy is indicated in selected patients whose allergic rhinitis remains highly bothersome despite conventional medical treatment with intranasal corticosteroid sprays and oral or topical antihistamines.2 The clinical effect is believed to derive from induction of T cells that produce interleukin 10 (regulatory T cells) and B cells that produce allergen specific IgG antibodies.3 Interleukin 10 has multiple anti-inflammatory properties, and grass pollen specific IgG blocks some of the actions of IgE, which largely mediates the immediate hypersensitivity reaction. Side effects mainly occur as IgE mediated reactions to the vaccines. Many clinical guidelines support use of Immunotherapy for treatment of refractory allergic rhinitis that affects quality of life, sleep, work, or social activities. A Cochrane …
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sublingual Immunotherapy world allergy organization position paper 2013 update
World Allergy Organization Journal, 2014Co-Authors: George Walter Canonica, Linda Cox, Moises A. Calderon, Jean Bousquet, Ruby Pawankar, Carlos E Baenacagnani, Michael S Blaiss, S Bonini, Enrico Compalati, Stephen R DurhamAbstract:We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual Immunotherapy;” “Clinical efficacy of sublingual Immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual Immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual Immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual Immunotherapy; “The future of Immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations.
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repeated low dose intradermal allergen injection suppresses allergen induced cutaneous late responses
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Giuseppina Rotiroti, Stephen J Till, Stephen R Durham, Mohamed H ShamjiAbstract:Background Subcutaneous Immunotherapy with high-dose grass pollen was first described more than 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. In contrast, low-dose subcutaneous Immunotherapy has not shown clinical benefit. Uncontrolled reports from the early 20th century describe low-dose allergen inoculation directly into the dermis, an immunologically active area containing abundant dendritic cells and lymphatics. Objective We sought to investigate the effect of low-dose intradermal grass pollen administration on cutaneous reactivity to allergen. Methods Thirty adults sensitized to grass and tree pollens were randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single intradermal injection at 10 weeks. At the end of the study, cutaneous early and late responses were measured after double-blind intradermal injection with grass and birch pollen. Results Participants who received 6 fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than control subjects who received 2 injections separated by 10 weeks ( P P Conclusion Low-dose intradermal allergen, like conventional subcutaneous high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in a manner that is allergen specific, systemic, and associated with induction of IgG antibodies.
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sublingual Immunotherapy for allergic rhinitis
Cochrane Database of Systematic Reviews, 2010Co-Authors: Suzana Radulovic, Moises A. Calderon, Duncan R Wilson, Stephen R DurhamAbstract:Background Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection Immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen Immunotherapy, particularly the sublingual route. Objectives To evaluate the efficacy of sublingual Immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. Search strategy The Cochrane Controlled Trials Register, MEDLINE (1966 to 2002), EMBASE (1974 to 2002) and SciSearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). Selection criteria All studies identified by the searches were assessed by the reviewers to identify randomised controlled trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data collection and analysis Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random-effects model. P values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Main results Twenty-two trials involving 979 patients were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for Parietaria, two for olive and one each for ragweed, cat, tree and Cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than six months, 10 studies for 6 to 12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallel group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.42, 95% confidence interval -0.69 to -0.15; p = 0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p = 0.00003) following Immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants were too small to make this a reliable conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data were available to analyse this factor. Authors' conclusions SLIT is a safe treatment which significantly reduces symptoms and medication requirements in allergic rhinitis. The size of this benefit compared to that of other available therapies, particularly injection Immunotherapy, is not clear, having been assessed directly in very few studies. Further research is required concentrating on optimising allergen dosage and patient selection.
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allergic rhinitis and its impact on asthma update allergen Immunotherapy
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Giovanni Passalacqua, Stephen R DurhamAbstract:The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific Immunotherapy have appeared. This review is intended as an update to the original document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection Immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of Immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection Immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual Immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual Immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual Immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for Immunotherapy are currently under evaluation, including the use of adjuvants, peptides, and DNA-conjugated and recombinant allergens.
Moises A. Calderon - One of the best experts on this subject based on the ideXlab platform.
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effect of 2 years of treatment with sublingual grass pollen Immunotherapy on nasal response to allergen challenge at 3 years among patients with moderate to severe seasonal allergic rhinitis the grass randomized clinical trial
JAMA, 2017Co-Authors: Guy W Scadding, Moises A. Calderon, Mohamed H Shamji, Aarif O Eifan, Martin Penagos, Florentina A Dumitru, Michelle L Sever, Henry T Bahnson, Kaitie Lawson, Kristina M HarrisAbstract:Importance Sublingual Immunotherapy and subcutaneous Immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous Immunotherapy and sublingual Immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual Immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Interventions Thirty-six participants received 2 years of sublingual Immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous Immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual Immunotherapy vs placebo at year 3. Subcutaneous Immunotherapy was included as a positive control. The study was not powered to compare sublingual Immunotherapy with subcutaneous Immunotherapy. Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual Immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [ P = .75]). Conclusions and Relevance Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen Immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. Trial Registration clinicaltrials.gov Identifier:NCT01335139; EudraCT Number: 2010-023536-16
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subcutaneous Immunotherapy and sublingual Immunotherapy comparative efficacy current and potential indications and warnings united states versus europe
Immunology and Allergy Clinics of North America, 2016Co-Authors: Harold S. Nelson, Melina Makatsori, Moises A. CalderonAbstract:Subcutaneous Immunotherapy and sublingual Immunotherapy are effective for allergic rhinitis and allergic asthma and with some support for use in selected patients with atopic dermatitis. The sequence of immunologic responses is the same, irrespective of the route of administration, and similar disease modification has been demonstrated. However, there are differences between the two approaches. The most important is the greatly reduced likelihood of sublingual Immunotherapy producing systemic reactions. There are major drawbacks for sublingual Immunotherapy in regard to dosing. Finally, there is the question of relative clinical efficacy, with the currently available data favoring subcutaneous Immunotherapy.
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basophil expression of diamine oxidase a novel biomarker of allergen Immunotherapy response
The Journal of Allergy and Clinical Immunology, 2015Co-Authors: Moises A. Calderon, Mohamed H Shamji, Janice A Layhadi, Guy W Scadding, Delica K M Cheung, Laurence A Turka, Deborah PhippardAbstract:Background Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of Immunotherapy withdrawal. Objective Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after Immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Methods Subcutaneous Immunotherapy (SCIT)–treated patients (n = 14), sublingual Immunotherapy (SLIT)–treated patients (n = 12), participants who completed 3 years of treatment with grass pollen sublingual Immunotherapy (the SLIT-TOL group; n = 6), patients with untreated seasonal allergic rhinitis (SAR; n = 24), and nonatopic control subjects (n = 12) were studied. Intracellularly labeled DAO + and surface expression of CD203c bright , CD63 + , and CD107a + on chemoattractant receptor-homologous molecule expressed on T H 2 lymphocytes (CRTh2)–positive basophils were measured by means of flow cytometry. Serum IgG 4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Results Proportions of allergen-stimulated DAO + CRTh2 + basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P + basophils expressing surface CD203c bright (all P P P P P Conclusion These results support long-term clinical and immunologic tolerance during and after grass pollen Immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after Immunotherapy.
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basophil expression of diamine oxidase a novel biomarker of allergen Immunotherapy response
The Journal of Allergy and Clinical Immunology, 2015Co-Authors: Moises A. Calderon, Mohamed H Shamji, Janice A Layhadi, Guy W Scadding, Delica K M Cheung, Laurence A Turka, Deborah PhippardAbstract:BACKGROUND: Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of Immunotherapy withdrawal. OBJECTIVE: Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after Immunotherapy. Results were compared with conventional basophil surface expression of activation markers. METHODS: Subcutaneous Immunotherapy (SCIT)-treated patients (n = 14), sublingual Immunotherapy (SLIT)-treated patients (n = 12), participants who completed 3 years of treatment with grass pollen sublingual Immunotherapy (the SLIT-TOL group; n = 6), patients with untreated seasonal allergic rhinitis (SAR; n = 24), and nonatopic control subjects (n = 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. RESULTS: Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P < .0001) compared with those in patients in the SAR group. Similarly, there were lower proportions of CRTh2(+) basophils expressing surface CD203c(bright) (all P < .001), CD63 (all P < .001), and CD107a (all P < .01). Rhinitis symptoms were lower in the SCIT, SLIT, and SLIT-TOL groups (P < .001) compared with those in the SAR group. Serum inhibitory activity for IgE-FAB and basophil histamine release were also significantly greater in all Immunotherapy groups (P < .05) compared with the SAR group. CONCLUSION: These results support long-term clinical and immunologic tolerance during and after grass pollen Immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after Immunotherapy.
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sublingual Immunotherapy world allergy organization position paper 2013 update
World Allergy Organization Journal, 2014Co-Authors: George Walter Canonica, Linda Cox, Moises A. Calderon, Jean Bousquet, Ruby Pawankar, Carlos E Baenacagnani, Michael S Blaiss, S Bonini, Enrico Compalati, Stephen R DurhamAbstract:We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual Immunotherapy;” “Clinical efficacy of sublingual Immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual Immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual Immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual Immunotherapy; “The future of Immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations.
Stephen J Till - One of the best experts on this subject based on the ideXlab platform.
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grass pollen Immunotherapy for treatment of allergic rhinitis
BMJ, 2014Co-Authors: Anna Slovick, Stephen J Till, Stephen R DurhamAbstract:A 33 year old female teacher presented with a history of troublesome allergic rhinoconjunctivitis and seasonal asthma. Since her teens, from May through to August she had experienced sneezing, nasal congestion, rhinorrhoea, itchy red eyes, and occasional breathlessness. In previous summers, her general practitioner had prescribed daily intranasal budesonide, oral cetirizine, and cromoglicate eye drops, together with inhaled salbutamol as needed. Although she had experienced a modest improvement with this treatment, symptoms continued to impair her concentration in the classroom and her quality of sleep. Her general practitioner referred her for consideration of “desensitisation.” Grass pollen Immunotherapy involves repeated administration of high doses of grass pollen allergen with the aim of inducing clinical and immunological tolerance in the recipient. Immunotherapy formulations contain an extract of one or more species of grass pollen and are administered either as a course of subcutaneous injections (“subcutaneous Immunotherapy”) or as daily sublingual drops or dissolving tablets (“sublingual Immunotherapy”) for three years. Experience with subcutaneous Immunotherapy, first described more than 100 years ago,1 is extensive; experience with sublingual Immunotherapy is less so. In the United Kingdom, grass pollen Immunotherapy is indicated in selected patients whose allergic rhinitis remains highly bothersome despite conventional medical treatment with intranasal corticosteroid sprays and oral or topical antihistamines.2 The clinical effect is believed to derive from induction of T cells that produce interleukin 10 (regulatory T cells) and B cells that produce allergen specific IgG antibodies.3 Interleukin 10 has multiple anti-inflammatory properties, and grass pollen specific IgG blocks some of the actions of IgE, which largely mediates the immediate hypersensitivity reaction. Side effects mainly occur as IgE mediated reactions to the vaccines. Many clinical guidelines support use of Immunotherapy for treatment of refractory allergic rhinitis that affects quality of life, sleep, work, or social activities. A Cochrane …
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repeated low dose intradermal allergen injection suppresses allergen induced cutaneous late responses
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Giuseppina Rotiroti, Stephen J Till, Stephen R Durham, Mohamed H ShamjiAbstract:Background Subcutaneous Immunotherapy with high-dose grass pollen was first described more than 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. In contrast, low-dose subcutaneous Immunotherapy has not shown clinical benefit. Uncontrolled reports from the early 20th century describe low-dose allergen inoculation directly into the dermis, an immunologically active area containing abundant dendritic cells and lymphatics. Objective We sought to investigate the effect of low-dose intradermal grass pollen administration on cutaneous reactivity to allergen. Methods Thirty adults sensitized to grass and tree pollens were randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single intradermal injection at 10 weeks. At the end of the study, cutaneous early and late responses were measured after double-blind intradermal injection with grass and birch pollen. Results Participants who received 6 fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than control subjects who received 2 injections separated by 10 weeks ( P P Conclusion Low-dose intradermal allergen, like conventional subcutaneous high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in a manner that is allergen specific, systemic, and associated with induction of IgG antibodies.
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grass pollen Immunotherapy induces mucosal and peripheral il 10 responses and blocking igg activity
Journal of Immunology, 2004Co-Authors: Kayhan T Nouriaria, Stephen J Till, J N Francis, Petra A Wachholz, M R Jacobson, Samantha Walker, Louisa K Wilcock, Steven Q Staple, Robert C Aalberse, Stephen R DurhamAbstract:T regulatory cells and IL-10 have been implicated in the mechanism of Immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during Immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen ( Phleum pratense , Phl P) Immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of Immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA + cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3 + T cells and CD68 + macrophages, respectively, whereas only 1–2% of total CD3 + cells and 4% of macrophages expressed IL-10. Following Immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-Immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG “blocking” activity correlated with the patients’ overall assessment of improvement. Thus, grass pollen Immunotherapy may induce allergen-specific, IL-10-dependent “protective” IgG4 responses.
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induction of il 10 cd4 cd25 t cells by grass pollen Immunotherapy
The Journal of Allergy and Clinical Immunology, 2003Co-Authors: J N Francis, Stephen J Till, Stephen R DurhamAbstract:Abstract Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either T H 2-to-T H 1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4 + CD25 + T cells. IL-10-producing CD4 + CD25 + regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. Objective: The aim of this study was to evaluate the role of IL-10 production and CD4 + CD25 + T cells in the response to grass pollen Immunotherapy. Methods: PBMCs were isolated from patients after 1 year of grass pollen Immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense , production of IL-10, IL-5, IL-4, and IFN-γ and proliferation and numbers of CD4 + CD25 + T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Results: Patients undergoing Immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing Immunotherapy, 116 ± 21 pg/mL [n = 11]; atopic patients, 30 ± 5 pg/mL [n = 11]; P + CD25 + cells identified after allergen stimulation was also greater in the Immunotherapy group. The numbers of CD4 + CD25 + T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the Immunotherapy group. Moreover, only T cells from patients undergoing Immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4 + CD25 + cells. Conclusion: Grass pollen Immunotherapy results in a population of circulating T cells that express the IL-10 + CD4 + CD25 + phenotype in response to allergen restimulation. (J Allergy Clin Immunol 2003;111:1255-61.)
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grass pollen Immunotherapy for hayfever is associated with increases in local nasal but not peripheral th1 th2 cytokine ratios
Immunology, 2002Co-Authors: Petra A Wachholz, Stephen J Till, Duncan R Wilson, Kayhan T Nouriaria, S M Walker, Adrienne Verhoef, S R DurhamAbstract:Grass pollen Immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after Immunotherapy. In a double-blind trial of grass pollen Immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of Immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the Immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the Immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen Immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.
Giovanni Passalacqua - One of the best experts on this subject based on the ideXlab platform.
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Sublingual grass and ragweed Immunotherapy: Clinical considerations - A PRACTALL consensus report
Journal of Allergy and Clinical Immunology, 2016Co-Authors: James T. Li, M. A. G. Calderon, Linda Cox, Oliver Pfaar, David I Bernstein, Giovanni Passalacqua, Thomas B Casale, Nikolaos G. PapadopoulosAbstract:Sublingual allergen Immunotherapy provides a new option for patients with allergic rhinitis in the United States. The efficacy of these sublingual Immunotherapy tablets in the treatment of allergic rhinitis has been firmly established in large multicenter clinical trials. In addition, the clinical benefits of sublingual Immunotherapy might persist after treatment is discontinued. Local reactions, such as gastrointestinal or oropharyngeal symptoms, are common. However, severe anaphylaxis is rare, and therefore the Immunotherapy tablets can be administered at home. Sublingual Immunotherapy for allergic rhinitis has been used successfully for years in Europe, and these products might be appropriate for patients who do not do well with standard drug therapy or for those who prefer a disease-modifying approach.
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allergic rhinitis and its impact on asthma update allergen Immunotherapy
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Giovanni Passalacqua, Stephen R DurhamAbstract:The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific Immunotherapy have appeared. This review is intended as an update to the original document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection Immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of Immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection Immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual Immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual Immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual Immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for Immunotherapy are currently under evaluation, including the use of adjuvants, peptides, and DNA-conjugated and recombinant allergens.
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harmful effect of Immunotherapy in children with combined snail and mite allergy
The Journal of Allergy and Clinical Immunology, 2002Co-Authors: Giovanni Battista Pajno, Stefania La Grutta, Giovanna Barberio, Giovanni PassalacquaAbstract:BACKGROUND: With respect to allergy, the possibility of cross-reactivity between snail and mite is well recognized, and anecdotal reports suggesting that allergen Immunotherapy with mite extract can worsen snail-induced allergy exist. OBJECTIVE: We describe the effect of Immunotherapy in 4 children with snail-mite allergy. METHODS: Four children (1 boy and 3 girls; 9-13 years of age) had consistent clinical histories (mild immediate respiratory symptoms after ingestion) and positive skin reactions for allergy to snail. They also had mite-induced asthma and were therefore prescribed subcutaneous specific Immunotherapy and subsequently followed. RESULTS: Several months (8-25) after starting Immunotherapy, all children experienced life-threatening reactions, anaphylaxis, and respiratory failure after inadvertent ingestion of snail. Skin reactivity to the fresh food increased in all patients. CONCLUSIONS: This observation confirms that in patients with combined mite-snail allergy, Immunotherapy should be avoided.
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randomised controlled trial of local allergoid Immunotherapy on allergic inflammation in mite induced rhinoconjunctivitis
The Lancet, 1998Co-Authors: Giovanni Passalacqua, M Albano, L Fregonese, A M Riccio, C Pronzato, Giuseppe Sandro Mela, Giorgio Walter CanonicaAbstract:Summary Background Non-injective routes of Immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral Immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy. Methods We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral Immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrolment and after 12 and 24 months of treatment. Findings We found significantly lower symptom scores in the Immunotherapy group than in the placebo group in most of the winter months (p=0·05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epitheliuim decreased significantly in the first year of treatment in the Immunotherapy group (p=0·04 and p=0·02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0·02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0·04). Immunotherapy was well tolerated and compliance was good. Interpretation Our results suggest that this Immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen.
Thomas B Casale - One of the best experts on this subject based on the ideXlab platform.
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Sublingual grass and ragweed Immunotherapy: Clinical considerations - A PRACTALL consensus report
Journal of Allergy and Clinical Immunology, 2016Co-Authors: James T. Li, M. A. G. Calderon, Linda Cox, Oliver Pfaar, David I Bernstein, Giovanni Passalacqua, Thomas B Casale, Nikolaos G. PapadopoulosAbstract:Sublingual allergen Immunotherapy provides a new option for patients with allergic rhinitis in the United States. The efficacy of these sublingual Immunotherapy tablets in the treatment of allergic rhinitis has been firmly established in large multicenter clinical trials. In addition, the clinical benefits of sublingual Immunotherapy might persist after treatment is discontinued. Local reactions, such as gastrointestinal or oropharyngeal symptoms, are common. However, severe anaphylaxis is rare, and therefore the Immunotherapy tablets can be administered at home. Sublingual Immunotherapy for allergic rhinitis has been used successfully for years in Europe, and these products might be appropriate for patients who do not do well with standard drug therapy or for those who prefer a disease-modifying approach.
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effect of pretreatment with omalizumab on the tolerability of specific Immunotherapy in allergic asthma
The Journal of Allergy and Clinical Immunology, 2010Co-Authors: Marc Massanari, Thomas B Casale, Harold S. Nelson, William W Busse, Farid Kianifard, Gregory P Geba, Robert K ZeldinAbstract:Background Although specific Immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease. Objective To evaluate omalizumab's effect on the tolerability of specific Immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. Methods This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific Immunotherapy to at least 1 of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after Immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. Results A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least 1 dose of Immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to Immunotherapy than those receiving placebo (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance Immunotherapy dose (110 [87.3%] vs 88 [72.1%], respectively; P = .004). Conclusion Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific Immunotherapy and enabled more patients to achieve the target Immunotherapy maintenance dose.
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omalizumab pretreatment decreases acute reactions after rush Immunotherapy for ragweed induced seasonal allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Thomas B Casale, William W Busse, Joel N Kline, Zuhair K Ballas, Mark H Moss, Robert G Townley, Masoud Mokhtarani, Vicki Seyfertmargolis, Adam Asare, Kirk BatemanAbstract:Background Rush Immunotherapy (RIT) presents an attractive alternative to standard Immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. Objectives We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. Methods Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 μg Amb a 1) or placebo Immunotherapy, then 12 weeks of omalizumab or placebo plus Immunotherapy. Results Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in Immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus Immunotherapy had fewer adverse events than those receiving Immunotherapy alone. Post hoc analysis of groups receiving Immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and Immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving Immunotherapy alone (0.69 vs 0.86; P = .044). Conclusion Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen Immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen Immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.
