PubMed | Karolinska Institutet, Hospital Clinico San Carlos IdISSC, James Cook University, University of Zürich and 43 more.
Type: | Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2016
The availability of allergen molecules (components) from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled component-resolved diagnosis (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology Users Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
PubMed | Karolinska Institutet, Mie National Hospital, Karolinska University Hospital, University of Southampton and 4 more.
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2015
The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. Aworkshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.
PubMed | St. Mary's University, Netherlands Anaphylaxis Networks, University of Manchester, University of Edinburgh and 11 more.
Type: Journal Article | Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2016
The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease.We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized.The findings from this review will be used to inform the development of recommendations for EAACIs Guidelines on AIT.
PubMed | Hospital Quironsalud Bizkaia, University of East London, Netherlands Anaphylaxis Networks, University of Manchester and 13 more.
Type: | Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2016
There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease.Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses.A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile.AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT.
PubMed | Red Cross, University of Zürich, Royal Sussex County Hospital, Hospital Medica Sur and 22 more.
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2016
This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.
PubMed | Allergy & Asthma Center Westend, Copenhagen University, Allergy Outpatient Clinic, Montpellier University and ALK
Type: Clinical Trial, Phase III | Journal: The Journal of allergy and clinical immunology | Year: 2016
The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease.This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR).The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score.Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 (P=.002) and 1.22 (P=.001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated.The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14weeks of treatment onward.
Hamilton R.G.,Johns Hopkins University |
Hamilton R.G.,Johns Hopkins Asthma and Allergy Center |
Kleine-Tebbe J.,Allergy & Asthma Center Westend
Current Allergy and Asthma Reports | Year: 2015
Application of purified native and recombinant allergenic molecules into IgE antibody assays can improve analytical sensitivity and specificity for selected allergen specificities. They enhance analytical sensitivity by allowing assays to detect IgE antibodies with a lower limit of quantification (LoQ) to missing or poorly represented allergens in diagnostic extracts that are commonly used in vivo and in vitro. Use of selected allergenic molecules can help improve the clinician’s prediction of the risk of a serious allergic reaction to stable allergens. They can provide diagnostic information to determine if a provocation challenge (e.g., oral food challenge) is indeed mandatory or not necessarily needed to support the final diagnostic decision. Suspected cross-reactivity based on the clinical history can be adjudicated by analyzing IgE antibodies to allergenic molecules from cross-reactive protein families. Finally, genuine primary sensitization can be identified by IgE antibody responses that are measured to selected allergenic molecules which are present in only one particular allergen source. After allergen-specific IgE detection, careful interpretation is required by the physician who knows the patient’s history. Applying single allergen molecules, positive IgE antibody results are still only relevant in the case of corresponding objective symptoms. Subsequently, clinical relevance of such an IgE antibody test result must be determined by the clinician and not by the test itself. Because of their comprehensive nature, allergen extracts will remain the principal allergen source for diagnostic in vivo and in vitro assays of IgE antibody for many years. Judicious use of individual allergenic molecules in serum IgE assays may provide their most cost effective and efficient application for establishing a definitive diagnosis of human allergic disease. © 2015, Springer Science+Business Media New York.
PubMed | Allergy & Asthma Center Westend, Johns Hopkins University and Charité - Medical University of Berlin
Type: Journal Article | Journal: Immunology and allergy clinics of North America | Year: 2015
Symptoms are recorded by obtaining a clinical history. Allergen sensitization is demonstrated by skin prick test or allergen-specific IgE serology. IgE sensitizations to allergen sources can be identified knowing the relationship between major aeroallergens and homologous allergen families. Some develop allergic sensitization to pan-allergens. Allergen extracts do not allow definitive separation of the sources. IgE antibody analysis of the major allergenic molecules facilitates differentiation of sensitizing allergen sources. IgE sensitizations to inhalant allergens are only relevant in the case of corresponding symptoms. In questionable cases, conjunctival or nasal provocation tests help induce confirmatory symptoms and identify relevant allergens for immunotherapy.
PubMed | National Jewish Health, Clinique Specialisee en Allergie de la Capitale, University of Cincinnati, Clinical Research Institute Inc and 2 more.
Type: Clinical Trial, Phase IV | Journal: The journal of allergy and clinical immunology. In practice | Year: 2016
Dual treatment with grass and ragweed sublingual immunotherapy (SLIT) tablets has not been studied.To characterize the safety and tolerability of dual grass and ragweed SLIT-tablet administration.This open-label, multicenter trial (NCT02256553) enrolled North American adults (N = 102) allergic to grass and ragweed. The trial had 3 periods, each of 2 weeks duration. In period 1, subjects received once-daily timothy grass SLIT tablet (2800 bioequivalent allergen unit; Merck, Inc, Kenilworth, NJ/ALK, Hrsholm, Denmark). In period 2, subjects received a short ragweed SLIT tablet (12 Ambrosia artemisiifolia 1-U; Merck/ALK) every morning and a grass SLIT tablet every evening. In period 3, subjects received once-daily grass and ragweed SLIT tablets within 5 minutes (simultaneous intake). The primary end point was the proportion of subjects with 1 or more local swelling events in each period. Secondary end points were the proportion of subjects with 1 or more local adverse events (AEs), that discontinued the treatment because of AEs, and subjects with 1 or more local AEs requiring treatment.No severe swellings, systemic allergic reactions, asthma attacks, or reactions requiring epinephrine were reported. Most (99%) AEs were graded mild to moderate. The proportions of subjects with 1 or more local swelling events were 14%, 22%, and 15% for periods 1, 2, and 3, respectively. For periods 1, 2, and 3, the proportions of subjects with 1 or more local AEs were 71%, 69%, and 56%, respectively; the proportions discontinuing the treatment because of treatment-related AEs were 5%, 1%, and 2%, and the proportions with 1 or more local AEs requiring treatment were 4%, 4%, and 1%.In this trial, a 4-week sequential SLIT-tablet dosing schedule followed by simultaneous intake of timothy grass and ragweed tablets was well tolerated.