Grass Pollen Exposure in an Environmental Exposure Chamber vs Natural Exposure: A Clinical Comparison of Symptoms.

Intérêt des chambres d’exposition environnementale dans l’évaluation des conjonctivites allergiques

Environmental exposure chambers in allergen immunotherapy trials: Current status and clinical validation needs

The potential of allergen challenges using environmental exposure facilities in allergic conjunctivitis drug development and more recently its implication on the diagnosis of the united airways concept have been emphasized in the recent literature. This study aims to present an overview of new and important data in this field. Standardized methodologies for ocular surface assessment during allergen challenges were described. The Total Ocular Symptom Score (TOSS) is the main validated questionnaire used for the assessment of ocular surface during allergen challenges. It combines patient and investigator assessments for more accurate conjunctival response and was extensively used in clinical research and daily practice. Environmental Exposure Chambers (EECs) studies aim to conduct tight-controlled challenges to a stable and well defined allergen airborne concentration, closer to natural exposure to evaluate the efficacy of nonpharmaceutical and antiallergic treatments. Recent studies showed a good correlation between ocular symptoms elicited by EEC and those assessed during natural exposure. These validated methods allow to investigate the efficacy of novel pharmacotherapies for allergic conjunctivitis and allergen immunotherapy (AIT) in a real-world model of allergen exposure. This study aims to summarize novel data regarding the impact of EECs in studying pathophysiology and drug efficacy in the context of existing clinical protocols related to ocular surface effects. In this regard, studies comparing conjunctival response during natural and EEC exposures in patients with pollen-induced conjunctivitis aimed to demonstrate better outcomes in tight-controlled exposures mimicking natural exposure. Because allergen challenges are widely implemented in allergy treatment, this article will focus on the most important outcomes and the evolution of treatments for allergic conjunctivitis.

Birch-induced allergic rhinitis: Results of exposure during nasal allergen challenge, environmental chamber, and pollen season

Background Previously, we identified a series of T-cell epitopes from the major cat allergen Fel d1 and showed these were safe and well-tolerated when administered to cat allergic subjects. In the current study, we evaluated persistence of the treatment effect (tolerance) one year after start of dosing for two treatment regimens with the same cumulative dose. Methods Subjects underwent Baseline Challenge in an Environmental Exposure Chamber (EEC) on 4 consecutive days, consisting of 3-hour allergen exposures (Fel d1 50.19±3.70 ng/m3). Subjects scored four nasal and four ocular symptoms every 30 minutes each on a scale of 0-3. 202 subjects were randomised to placebo, 8x3nmol Cat Peptide Antigen Desensitisation (Cat-PAD) 2weeks(wk) apart or 4x6nmol Cat-PAD 4wk apart. Subjects re-attended the EEC for 4 consecutive days, of 3-hours, 18-22wk after the start of treatment. 50-54wk after commencement of treatment subjects were invited to participate in a blinded follow-on study without further dosing. 89 subjects were enrolled and had a further 4 consecutive days, of 3-hours in the EEC.

Self-reported symptoms of grass allergic subjects correlate positively with symptom scores recorded in a controlled environment

BackgroundEnvironmental exposure chambers (EECs) have been used extensively to study allergic rhinoconjunctivitis. Few studies have been published using EECs in conjunctivitis only, and none have used conjunctival allergen challenge as a selection criterion. The present study validated ALYATEC EEC in allergic conjunctivitis to birch pollen.MethodsSixteen patients with a positive conjunctival allergen challenge (CAC) were exposed to 60 ng/m3 of Bet v 1 in an EEC on two consecutive days for a maximum of 4 h to validate EEC exposure to birch. Reproducibility was tested among seven of the patients. A conjunctival positive scoring during the CAC and the EEC exposure was defined as a Total Ocular Symptom Score (TOSS) ≥ 5.ResultsFifty percent of patients had a conjunctival positive scoring during first exposure and 75% during second exposure. The mean time to a conjunctival response was 81.2 ± 33.9 min and 101.6 ± 57 (P > 0.05) during first and second exposure, respectively. No difference in TOSS occurred between the two exposures. The time necessary to obtain a positive response during the CAC was significantly shorter than with the EEC. The estimated quantity of Bet v 1 inducing a positive response was 0.07 ± 0.03 ng (exposure 1), 0.07 ± 0.07 ng (exposure 2), 980 ± 784 ng (CAC). Conjunctival positive scoring and quantity of Bet v 1 was reproducible in all six EEC exposures.ConclusionsEarly conjunctival responses induced by birch allergen exposures in EEC were different than from those identified with direct instillation during CAC. EEC appears to be closer to natural exposure than CAC.

Validation of the Global Allergy and Asthma European Network (GA2LEN) chamber for trials in allergy: Innovation of a mobile allergen exposure chamber

A variety of different environmental exposure chambers (EECs) have been used to evaluate treatments for allergic rhinitis. To describe and test a system for a homogenous distribution of grass pollen, Phleum Pratense, in an EEC to be used for controlled pollen exposure studies in allergic participants. A chamber made of stainless steel with completely rounded corners, seating four individuals at a time, was used. Room pressure, temperature, humidity and the air change rate were kept constant throughout the study period. A rotating pipette dispensed a uniform supply of pollen into a turntable's v-shaped grooves. A stainless steel capillary tube sucked the pollens into a venturi throat at which time the pollens were mixed with a high-pressure airstream of compressed high-efficiency particulate arrestance filtered air and then transported to a spreading plate inside the EEC. To achieve uniform concentrations in the EEC, the turntable's rotating speed was continuously adjusted using information from video-coupled feedback and feed forward mechanisms. Pollen levels were detected using standard volumetric air samplers and laser particle counters. The target pollen exposure level was 1000 pollens/m(3) . Twenty-one participants were exposed to pollens in the EEC twice for 210 min. Participants evaluated their symptoms every 30 min using a total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching and sneezing. Across fifteen study days, the average pollen level was 982 pollens/m(3) (SD, 102 pollens/m(3) ). On average, participants experienced a 10% difference in overall pollen levels between their two visits to the EEC. The mean TNSSs rose throughout the exposure period, with a low at baseline of 0.43 (SD, 0.68) to a high of 4.71 (SD, 2.43) just before exiting the EEC. This EEC provides a reproducible, precise and homogenous distribution of pollens making it suitable for single-centre allergy clinical trials.

An environmental exposure chamber (EEC) is a health facility that enables allergic symptoms to be induced in a controlled manner in persons sensitized to a dispersed allergen. We performed a study at our institution to technically and clinically validate an EEC in patients allergic to grass pollen. We developed a new EEC inside a clean room (ISO-8 class) measuring 15.6 m². During the technical validation, the patient's exposure conditions were simulated by ensuring homogeneous distribution of the allergen with a particle disperser and monitoring both particle and pollen grain concentrations. Temperature, pressure, and humidity were also registered. A total of 31 volunteers were exposed to Phleum pratense pollen in the EEC. Of these, 25 were allergic (cases), with symptoms of rhinoconjunctivitis with or without asthma, and 6 were not (controls). One control and 2 cases were exposed twice to check reproducibility, generating a total of 34 challenges. The test was stopped once the positivity criterion was reached or the patient completed 90 minutes in the EEC. Both the stability of particle concentrations and approximation to the pollen sample concentration were guaranteed. All challenges with controls were negative. Among the cases, 15% of challenges were negative and 85% were positive. No severe or late reactions were observed. Volunteers exposed twice to the same pollen had the same result in both challenges. Our EEC proved to be a specific, safe, and reproducible tool for the diagnosis of grass pollen allergy.

Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen

Characterization of Self-Reported Pollen Food Syndrome (PFS) in Birch Allergic Subjects Exposed to Birch Pollen in an Environmental Exposure Chamber (EEC) in Canada

Objective: Environmental Exposure Chamber (EEC) should have standardized and controlled allergenic and non-allergenic exposures to perform reproducible clinical studies. The aim was to demonstrate that mite exposure in the Alyatec® EEC could induce early (EAR) and/or late asthmatic reactions (LAR) in at least 60% of subjects allergic to mite.Methods: The EEC has a volume of 147-m3 with 20 seats. The nebulized particle number, airborne Der p1, endotoxins, and volatile organic compound (VOC) concentrations were measured. Twenty-four asthmatics allergic to mite were randomly exposed to 15, 25, and 46 ng/m3 Der p1. Specificity was assessed in not mite-sensitized asthmatics.Results: No significant endotoxin or VOC contamination was measured. The mean inter-assay CVs were 12.5% for the airborne particle number and 28.7% for airborne Der p1 concentrations. For the three Der p1 concentrations, at least 88% of the subjects developed EAR and/or LAR, and at least 46% developed a dual response. No reaction occurred with placebo or in the control group. No severe bronchial reaction occurred.Conclusions: The Alyatec® EEC demonstrated a tight control of allergenic and non-allergenic exposures. The EEC was clinically validated, with airborne Der p1 levels close to levels found in natural settings.

Patients report nasal congestion as the most bothersome seasonal allergic rhinitis (SAR) symptom. Measurement of this symptom in previous research has largely been based on subjective patient ratings. This study was designed to measure efficacy, onset, and duration of action of the corticosteroid mometasone furoate nasal spray (MFNS) on nasal congestion using an environmental exposure chamber (EEC) and the objective assessment acoustic rhinometry (AcR). In a randomized, double-blind, placebo-controlled study, ragweed-sensitive subjects were exposed to ragweed pollen (3500 ± 500 pollen grains/m(3)) in an EEC (day 1). Subjects rated instantaneous total nasal symptom score (TNSS), including NSS for congestion (NSS-C). Qualifying subjects received MFNS, 200 micrograms, or placebo and rated postdosing symptoms; a subset received MFNS, 200 micrograms, or placebo q.d. for 6 subsequent days, returning to EEC on day 8. Days 1 and 8 assessments included AcR, TNSS, and the Rhinoconjunctivitis Quality of Life Questionnaire developed for use in the EEC (RQOLQ-EEC). At day 1, hour 6, patients receiving MFNS (n = 155) reported significantly reduced congestion versus placebo (n = 155) per AcR and NSS-C after one dose, showing numerically superior TNSS change from baseline (p = NS). Among the subset who received 6 additional days of treatment, MFNS (n = 78) yielded significantly lower TNSS versus placebo (n = 77) before day 8 EEC entry and throughout 4-hour exposure (p < 0.05), except at 3.5 hours. AcR showed lower congestion with MFNS versus placebo before day 8 EEC exposure and at 24 and 26 hours after final dose (p < 0.05 for all). AcR and NSS-C correlated at multiple time points. Day 8 RQOLQ-EEC between-group scores were significantly different (p = 0.02) for practical problems. MFNS, 200 micrograms, showed onset of nasal congestion relief at 6 hours and duration of action beyond 24 hours postdosing. Objective and subjective assessments were correlated in subjects with maximal (placebo) or minimal (MFNS treatment) congestion symptoms; both assessments were correlated with improved QOL.

Background : A low dose naturalistic allergen challenge model to study mild asthmatics would aid in the development of effective drug therapies. We investigated both model specificity and SPT or IgE classification as a predictor of change in lung function and lower airway symptoms in asthmatics. Methods : A meta-analysis was conducted on 323 subjects (53 mild asthmatics) with a history of cat allergy and positive SPT to cat allergen. Subjects were exposed to airborne cat allergen in a naturalistic Environmental Exposure Chamber (EEC) model for 3 hrs over 4 consecutive days. FEV 1 was assessed before and after EEC and asthma symptom scores were recorded every 30 mins in the EEC. Results : Low dose airborne naturalistic challenge resulted in: 1) A consistent drop in FEV 1 over 4 days allergen challenge. Asthmatics have a greater reduction in FEV 1 (L) over all days (p≤0.001). 2) Increase in SPT moderately predicts a larger decline in lung function. 3) Increase in IgE class (C) predicts a larger drop in lung function (ΔFEV 1 (L)) with allergen exposure: IgE ≥ C1 = 0.56 ± 0.06L vs. 0.31 ± 0.02L (p≤0.001); IgE ≥ C2= 0.59 ± 0.06L vs 0.34 ± 0.02L (p≤0.001); and IgE ≥ C3=0.66 ± 0.08L vs 0.44 ± 0.03L (p=0.01) in asthmatics compared to non-asthmatics, respectively. 4) Asthma symptom scores were higher in asthmatics than non-asthmatics (Mean Score 3.23 ± 0.30 vs. 2.60 ± 0.12 (p=0.05)). 5) Neither SPT or IgE class is predictive of asthma symptoms with allergen exposure. Conclusions : The EEC Asthma Model represents a more naturalistic model for the study of asthma. IgE and SPT are useful to characterize asthmatic patients and safely predict their response in the EEC.