Background
The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions.
Objective
We aimed to ...assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC).
Methods
Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure.
Results
An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non‐specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05).
Conclusion
Prick test size and non‐specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR.
Prick test diameter and non‐specific bronchial hypersensitivity level were independent predictive factors of early asthmatic response (EAR) during allergen exposure in an environmental exposure chamber (EEC). Severity of rhinitis and conjunctivitis were related to asthma symptoms induced by allergen exposure both during EAR and late asthmatic response (LAR).
The seventh “Future of the Allergists and Specific Immunotherapy (FASIT)” workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and ...industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the “Therapy Allergen Ordinance” in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future.
Background
Topical mast cell stabilizers were previously shown to treat the signs and symptoms of seasonal and perennial allergic conjunctivitis safely and effectively in active and ...placebo‐controlled trials. However, mast cell stabilizers have not been compared to topical corticosteroids for efficacy. We tested the non‐inferiority of a topical mast cell stabilizer, N‐acetyl aspartyl glutamic acid (4.9%, NAAGA), compared to fluorometholone (0.1%, FM) during controlled exposures to the airborne birch pollen allergen, Bet v 1, in an environmental exposure chamber (EEC).
Methods
This randomized, cross‐over, investigator‐blinded study included 24 patients with a history of birch pollen allergic conjunctivitis. Patients were randomized to 5 days of treatment with NAAGA, then FM (n = 12) or FM, then NAAGA (n = 12). After each treatment, patients were exposed to a fixed airborne concentration of Bet v 1 in ALYATEC EEC. The primary endpoint was the amount of allergen required to trigger a conjunctival response (Abelson score ≥5). Groups were compared with a linear model for cross‐over studies. Non‐inferiority was assumed, when the lower bound of the risk ratio confidence interval (CI) was >0.5.
Results
At screening, the mean time‐to‐conjunctival response was 72.5 ± 35.9 min. NAAGA and FM extended the response time to 114.8 ± 55.0 and 116.6 ± 51.5 min respectively. The mean amounts of allergen required to trigger a conjunctival response were 1.165 ng after NAAGA and 1.193 ng after FM treatment. The risk ratio for the conjunctival response was 0.977 (95% CI: 0.812; 1.174), which indicated non‐inferiority. Adverse events occurred less frequently with NAAGA (29.2%) than with FM (58.3%).
Conclusion
In patients with allergic conjunctivitis to birch pollen, NAAGA was non‐inferior to FM in exposures to airborne Bet v 1. The EEC was a good model for simulating real‐life airborne allergen exposure and for demonstrating the efficacy and safety of eye drops for treating allergic conjunctivitis.
Trial registration
Not registered.
This randomized, cross‐over, investigator‐blinded study evaluated the non‐inferiority of N‐acetyl aspartyl glutamic acid (4.9%, NAAGA) compared to fluorometholone (0.1%, FM) during controlled birch allergen exposures. NAAGA was non‐inferior to FM as the mean amounts of allergen and time required to trigger a conjunctival response were not different in both groups (risk ratio for conjunctival response of 0.977 (95% CI: 0.812; 1.174)).
Purpose of Review
The goal of this review is to compress all important information and results of the research in reducing cat allergen exposure using air filtration. Fel d 1 is the major allergen ...responsible for IgE responses in 90 to 95% of patients with cat allergy.
Recent Findings
Reduction of cat allergen in indoor air with different air filtration systems and portable devices has been demonstrated in the majority of the studies. Recently, early and late asthmatic responses were significantly reduced using portable HEPA air cleaners in an environmental exposure chamber.
Summary
This review provides a comprehensive overview of the current state of airborne Fel d 1 air filtration targeting the most efficient devices in cat allergen reduction. Novel emerging HEPA filters are targeting reduction of cat indoor asthma trigger so patient can might benefit from efficient solution.
If allergen immunotherapy (AIT) is to be considered as a treatment option for allergic asthma, it must undergo the same developmental steps as other antiasthmatic drugs. The bronchial allergen ...challenge model has demonstrated excellent negative predictive value for the development of new therapies for asthma. Subcutaneous immunotherapy appears to have a clinical and significant effect on the early asthmatic response to mite, cat, and birch and grass pollens in children and adults. Use of AIT in children with asthma is widely practiced but not supported by as strong a level of evidence as in adults. House dust mite sublingual immunotherapy tablets demonstrate efficacy in asthma exacerbations and other outcomes when used as add-on therapy in adult patients. Using a biologic to improve the patient’s lung functions and asthma control before initiating AIT can transform unsuitable candidates for AIT into appropriate candidates. Because AIT is a form of personalized medicine, phenotyping the most suitable patient is necessary. Field studies of adults and children have suggested that polysensitized patients with rhinitis and Global Initiative for Asthma class 2 to class 4 asthma appear the most likely to be good responders. We hypothesized that AIT responders are those who demonstrate a high eosinophilic response to natural or experimental exposure.
Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non‐allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological ...features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma).
In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose‐finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated.
On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments.
Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non‐contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed.
Background An immunotherapy formulation consisting of 3 contiguous overlapping peptides (COPs) derived from Bet v 1, the major birch pollen allergen, showed good clinical tolerability in a previous ...phase I/IIa clinical trial. Objectives We sought to evaluate the efficacy and safety of allergen-specific immunotherapy using 2 dose regimens of Bet v 1 COPs versus placebo in subjects with birch pollen–induced allergic rhinoconjunctivitis. Methods A randomized, double-blind, placebo-controlled phase IIb clinical trial was performed to assess the efficacy of Bet v 1 COP immunotherapy during the 2013 birch pollen season. Before the season, Bet v 1 COPs (50 and 100 μg in aluminum hydroxide) or placebo (saline and aluminum hydroxide) were administered as 5 subcutaneous injections to 239 adults with allergic rhinoconjunctivitis to birch pollen. Bet v 1 COPs at 25 or 50 μg were administered on day 1, and 50 or 100 μg was administered on days 8, 15, 29, and 57, respectively. Patients were monitored for adverse events during the treatment period and assessed for combined rhinoconjunctivitis symptom and medication scores, as well as quality of life. Results Rhinoconjunctivitis symptom and medication scores improved in both Bet v 1 COP–treated groups, reaching statistical significance over placebo in the 50-μg group (least squares mean, −0.23; 26% improvement; P = .015). Both active groups showed significant improvement in quality of life and nighttime nasal symptom scores, supporting the primary end point findings. Bet v 1 COP injections were well tolerated, with a higher frequency of systemic adverse events in the 100-μg group. Conclusion Two months of preseasonal immunotherapy with 3 COPs derived from Bet v 1 at a 50-μg dose showed promising efficacy, small risk for systemic reactions, and immunomodulatory changes in this single-season, dose-finding, phase IIb trial in patients allergic to birch pollen.
Background While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is ...reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma. Methods Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined. Results Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 ( P < .001). The omalizumab group also showed an overall increase in FEV1 compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed. Conclusions Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab. Trial registry ClinicalTrials.gov ; No.: NCT01007149 ; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu
Diagnosis and immunotherapy of house-dust mite (HDM) allergy is still based on natural allergen extracts. The aim of this study was to analyze commercially available Dermatophagoides pteronyssinus ...extracts from different manufacturers regarding allergen composition and content and whether variations may affect their allergenic activity.
Antibodies specific for several D. pteronyssinus allergens (Der p 1, 2, 5, 7, 10 and 21) were used to analyze extracts from 10 different manufacturers by immunoblotting. Sandwich ELISAs were used to quantify Der p 1 and Der p 2 in the extracts. Mite-allergic patients (n = 45) were skin-tested with the extracts and tested for immunoglobulin E (IgE) reactivity to a panel of 10 mite allergens (Der p 1, 2, 4, 5, 7, 8, 10, 14, 20 and 21) by dot blot.
Only Der p 1 and Der p 2 were detected in all extracts but their concentrations and ratios showed high variability (Der p 1: 6.0-40.8 µg ml(-1); Der p 2: 1.7-45.0 µg ml(-1)). At least 1 out of 4 allergens (i.e. Der p 5, 7, 10 and 21) was not detected in 8 of the studied extracts. Mite-allergic subjects showed different IgE reactivity profiles to the individual mite allergens, the extracts showed different allergenic activity in skin-prick tests and false-negative results.
Commercially available D. pteronyssinus extracts lack important allergens, show great variability regarding allergen composition and content and some gave false-negative diagnostic test results in certain patients.
The challenge of delabeling amoxicillin allergy is an important issue for patients and clinicians, especially when anaphylaxis is reported. A recent study has proposed a clinical decision rule, ...PEN-FAST, to identify low-risk penicillin allergies.
To validate the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy and to identify clinical predictive factors of amoxicillin immediate hypersensitivity.
We retrospectively analyzed medical records of patients with a suspected immediate amoxicillin allergy who carried out an allergologic evaluation by a specialist in the Allergy Unit of Strasbourg University Hospital from 2015 to 2020.
A total of 142 adult patients (88 women 62.0%; median age, 52 interquartile range, 40.3-62.0 years) were analyzed. Most of them reported anaphylaxis (68.8%). Internal validation of PEN-FAST score revealed a good discrimination with area under the curve of 0.86 (95% confidence interval, 0.79-0.92). A cutoff of less than 3 points for PEN-FAST was used to classify 29 from 142 patients at low risk of allergy, of whom only 2 (6.9%) received positive results of allergy testing. The negative predictive value for successful delabeling was 0.93 (95% confidence interval, 0.77-0.99). Predictive clinical features for immediate amoxicillin hypersensitivity were time since reaction (P < .001), time elapsed between drug intake and first symptom (P < .001), severity grade reaction (P < .001), and treatment or hospitalization required (P < .001).
PEN-FAST has been validated to identify low-risk penicillin allergies in our European cohort of patients mainly reporting anaphylaxis. This is the first reported external validation of a penicillin allergy clinical decision rule internationally.
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