Environmental Exposure Chamber Research Articles

Onset of efficacy of azelastine hydrochloride 0.15% nasal spray for allergic rhinitis in an environmental exposure chamber

BackgroundAzelastine nasal spray is effective in relieving symptoms of seasonal and perennial allergic rhinitis. ObjectiveTo evaluate the time to onset of efficacy of azelastine hydrochloride (HCl) 0.15% vs placebo in participants with seasonal allergic rhinitis. MethodsA total of 110 participants aged 18 to 65 years were randomized to receive azelastine HCl 0.15% 2 sprays per nostril vs placebo nasal spray after being continuously exposed to ragweed pollen in an environmental exposure chamber. Symptoms were evaluated subjectively by the total nasal symptom score (TNSS) scale. The primary efficacy parameter was the time to onset of efficacy of azelastine as measured by the change from baseline in TNSS 15, 30, 45, 60, 90, 120, 180, and 240 minutes post-dose. ResultsThe azelastine nasal spray group had statistically significant improvement in TNSS compared with placebo 30 minutes post-dose (P = .0002), and the effect was sustainable throughout the environmental exposure chamber session for all subsequent time points (P < .0001). Adverse events were mild, including bitter taste, nasal discomfort, epistaxis, sinusitis, and nausea. No major adverse events were reported during the study. ConclusionAzelastine HCl 0.15% nasal spray relieves nasal symptoms associated with allergic rhinitis and has a fast onset of action within 30 minutes. The overall safety profile of azelastine has also been proven to be safe. These results, along with previous findings on efficacy and improved quality of life for people with allergic rhinitis, establish the important clinical role of azelastine HCl 0.15%. Trial RegistrationClinicalTrials.gov Identifier: NCT04264637.

Rhinoconjunctivitis severity induced by cat exposure influences early and late asthmatic responses: Evidence from an environmental exposure chamber.

The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions. 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). 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. 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). 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.

A Replicate Phase III Clinical Trial to Assess the Reproducibility of Efficacy and Safety of Reproxalap Ophthalmic Solution (0.25%) Compared to Vehicle in Participants With Seasonal Allergic Conjunctivitis (AC) Using the Environmental Exposure Chamber (EEC)

A Replicate Phase III Clinical Trial to Assess the Reproducibility of Efficacy and Safety of Reproxalap Ophthalmic Solution (0.25%) Compared to Vehicle in Participants With Seasonal Allergic Conjunctivitis (AC) Using the Environmental Exposure Chamber (EEC)

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

BackgroundPollen variation can affect field study data quality. Nasal allergen challenge (NAC) is considered the gold standard for evaluating allergic rhinitis, while environmental exposure chambers (EECs) are mainly used in phase 2 drug development studies. We aimed to study birch-induced allergic rhinitis under 3 different conditions. MethodsThis study included 30 participants allergic to birch pollen, based on birch skin prick test, specific immunoglobulin E (IgE), and positive NAC. Participants were exposed to placebo twice, followed by 2 consecutive 4-h birch airborne exposures, repeated on 2 occasions to evaluate reproducibility and priming effect. Nasal response was defined as total corrected nasal symptom score (ΔTNSS) ≥ 5 during NAC and EEC. The primary end-point was to measure TNSS during the last 2 h of first allergen exposure. TNSS was also analyzed during natural exposure. ResultsThe dose most commonly yielding positive TNSS during NAC was 175.2 ng/200 μL. Eighteen participants experienced ΔTNSS ≥5 during the last 2 h of the first exposure, whereas 21 had positive responses at all 4 exposures. Mean ΔTNSS was 1 with placebo versus 6 with birch. Exposures were reproducible, with no observed priming effect. Airborne Bet v 1 was 25 ng/m3, while the pollen measurement was 279/m3 during pollen season. TNSS reached 5 in 67.9% of participants during peak pollen season. ConclusionEEC outcomes were similar to those obtained with NAC and natural exposure, suggesting the usefulness of EEC in allergic rhinitis studies. The primary end-point was reached, as 60% of participants experienced nasal responses.

Efficacy of medical face masks on birch-induced asthma in ALYATEC EEC

To control the spread of SARS-CoV-2, the use of face masks has become widespread worldwide. There is no clinical evidence that medical masks are efficient in pollen-induced asthma. We studied the efficacy of medical face masks in reducing asthma in patients allergic to birch in ALYATEC Environmental Exposure Chamber (EEC).

Asthma responses in birch allergic rhinitis (AR) with and without known birch-related asthma

Birch pollen mainly induces allergic rhinoconjunctivitis. A considerable discordance between patient reported asthma symptoms and objective asthma responses was observed during birch allergen challenges in ALYATEC Environmental Exposure Chamber (EEC).

Évaluation clinique de l’efficacité d’un masque chirurgical dans la réduction des symptômes d’asthme et de rhinite, chez des sujets allergiques au pollen de bouleau dans la chambre d’exposition environnementale ALYATEC

Aim of the studyCurrently, there is no clinical evidence that face masks are efficient in birch pollen-induced asthma. As the use of face masks has become widespread worldwide to limit the spread of SARS-CoV-2, it was chosen to demonstrate the clinical efficacy of medical masks in patients allergic to birch in the same way that clinical trial with drugs. Patients and methods24 birch-related asthmatic patients, were exposed to 60ng/m3 of airborne Bet v 1 in ALYATEC environmental exposure chamber. All patients had positive skin prick tests and specific IgE to birch at screening visit. Patients with asthma response during 1-hour baseline exposure were randomized into 2 groups: with and without a KOLMI® surgical face mask (OP-Air), for a 6-hour exposure to birch allergen. ResultsThe median time to obtain an early asthma response in the group without mask was 37minutes, and 67min in the group with mask (P=0.219). At 1 hour-exposure, patients with masks still present in the environmental exposure chamber was twice as much as the group without masks. ConclusionThis pilot study showed a tendency of face masks to increase the time to develop allergic symptoms.

ONSET OF ACTION OF AZELASTINE HCL NASAL SPRAY 0.15% EVALUATED IN AN ENVIRONMENTAL EXPOSURE CHAMBER

<h3>Introduction</h3> Azelastine nasal spray is an effective treatment in managing seasonal allergic rhinitis (SAR). The objective of this single center, double-blinded, placebo-controlled study was to evaluate the time to onset of efficacy of azelastine HCl 0.15% in the relief of nasal symptoms of SAR in an environmental exposure chamber (EEC). <h3>Methods</h3> 110 participants aged 18 to 65 years were randomized to receive azelastine HCl 0.15% or placebo nasal spray after being continuously exposed to ragweed pollen in an EEC. The primary efficacy parameter was the time to onset of efficacy of azelastine as measured by the change from baseline in total nasal symptom score (TNSS) versus placebo. <h3>Results</h3> Azelastine HCl 0.15% demonstrated a statistically significant improvement in TNSS compared with placebo starting from 30 minutes post-dose (p=0.0002), and the effect was sustainable at all time points throughout the end of the EEC session at 240 minutes post dose (p= <0.0001). Adverse events observed was consistent with known safety profile. No serious adverse events or other significant AEs were reported. <h3>Conclusions</h3> This is the first study assessing the onset of action of azelastine HCl 0.15% in an EEC, demonstrating a fast onset in 30 minutes. Azelastine HCl 0.15% nasal spray was well tolerated and there were no safety concerns raised during this SAR study. The rapid onset of action for the relief of allergy symptoms combined with a safe side effect profile indicate azelastine HCl 0.15% is a valuable treatment option for allergic rhinitis.

Efficacy of N-acetyl aspartyl glutamic acid versus fluorometholone for treating allergic conjunctivitis in an environmental exposure chamber.

BackgroundTopical 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).MethodsThis 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.ResultsAt 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%).ConclusionIn 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 registrationNot registered.

A Phase III Double-Masked, Crossover, Vehicle-Controlled Clinical Trial Conducted in an Environmental Exposure Chamber (EEC) to Study Reproxalap, a Novel, Non-Antihistaminic, Non-Steroidal, Reactive Aldehyde Species Inhibitor for the Treatment for Allergic Conjunctivitis (AC)

Reproxalap demonstrated significant reduction in AC signs/symptoms over Phases I-II clinical trials; therefore, a pivotal phase III study was conducted in an EEC which mimics the natural but controlled exposure to allergen, to test reproxalap’s efficacy for AC treatment (NCT04207736).

P024 THE ENVIRONMENTAL EXPOSURE CHAMBER: A REAL WORLD YET CONTROLLED APPROACH TO ALLERGIC CONJUNCTIVITIS TRIALS

Allergic Conjunctivitis (AC) affects 15-20% of the worldwide population. Environmental exposure chamber (EEC) may facilitate clinical trials as it mimics natural allergen exposure, in a controlled setting which may aid in the selection of adequately allergic AC subjects.

Birch allergen challenges in allergic conjunctivitis using standard conjunctival allergen challenge and environmental exposure chamber.

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.

Carbon Dioxide Inhalation Mitigates Functional Deficits Elicited by Blast‐Induced Traumatic Brain Injury

Traumatic Brain Injury (TBI) is a significant public health burden affecting nearly 3 million individuals within the US alone annually. Large amounts of research dollars have been spent attempting to ameliorate the effects of TBI, however these efforts have failed to reduce injury rates or minimize the effects of primary injury incurred during activities such as contact sports or active military deployment. Preclinical and clinical work has revealed that mitigating brain SLOSH during cranial rotation or impact provides a profound protective effect against the effects of TBI. The biologic mechanism behind SLOSH mitigation is a filling of the compensatory reverse volume (CRV) of the skull, an effect that minimizes brain movement and the imparting of external forces on brain tissue. The most powerful biologically controllable determinant of CRV and intracranial pressure (ICP) is partial pressures of carbon dioxide (CO2, pCO2) within the bloodstream. We hypothesize that increased CO2 inhalation acting to minimize the CRV acts to minimize SLOSH and is therefore protective in the context of TBI. To initiate testing this hypothesis, we have combined increased environmental CO2 exposure with a murine model for blast-induced TBI. Murine subjects exposed to 5% CO2 for a period of 10 min in an environmental exposure chamber prior to TBI or sham treatments exhibited an increase in freezing behavior, indicative of actual exposure to gas composition, as compared to their medical grade atmospheric air counterparts. TBI treatment resulted in a significant increase in righting reflex time (RRT) as compared to sham treatment, an effect mitigated by prior inhalation of 5% CO2. Three hours post-injury, TBI results in a significant reduction in general exploratory locomotor activity as compared to sham treatment, an effect that is also mitigated by prior inhalation of 5% CO2. Inhalation of CO2 however was found to have no effect on TBI-elicited increases in cortical tnf-α mRNA expression indicative of a complex biologic mechanism behind observed physiologic effects. Future studies will seek to ascertain molecular adaptations associated with the ability of CO2 to mitigate TBI-induced effects in vivo. These studies provide the first in vivo evidence identifying a targetable biologic mechanism to reduce the effects of primary injury and may lead to viable medical devices and methodologies for the prevention of mild TBI in contact sports and/or military operations.

Effects of ectoine containing nasal spray and eye drops on symptoms of seasonal allergic rhinoconjunctivitis.

BackgroundPatients are often dissatisfied with the symptom control obtained from available pharmacological treatments for seasonal allergic rhinoconjunctivitis (ARC). Therefore, patients seek for alternative, nonpharmacological options to treat their symptoms. Here, we assessed the efficacy of ectoine nasal spray and ectoine eye drops in comparison to placebo to prevent nasal and ocular symptoms following exposure to pollen in patients with ARC.MethodsIn this double‐blind, randomized, placebo‐controlled, cross‐over study, 46 patients with ARC applied ectoine eye drops and nasal spray in immediate succession or placebo eye drops and nasal spray for 13 days before ARC symptoms were induced in an environmental exposure chamber. Primary endpoint was the baseline‐adjusted area under the curve (AUC) posttreatment total nasal symptom score (TNSS) and the total ocular symptom score (TOSS) using analysis of covariance. Secondary endpoints were, amongst others, total nonnasal symptoms score (TNNSS) and nasal patency (measured using acoustic rhinometry).ResultsTreatment with both ectoine and placebo reduced TNSS, TOSS, and TNNSS upon allergen exposure. The analysis of parameters at baseline and after allergen exposure demonstrated that ectoine induced a clinically relevant improvement in ARC symptoms compared to placebo: the least square mean difference for baseline‐adjusted AUC was ‒1.87 for TNSS, ‒1.45 for TOSS and ‒2.20 for TNNSS. The mean change from baseline AUC of TNNSS for ectoine was also significantly greater than for placebo (‒5.49 vs. ‒3.46; p = 0.011). Ectoine significantly improved the singular symptoms “sneezing,” “watery eyes” and “itchy eyes” (p ≤ 0.021) as well as “itchy ear/palate” (p = 0.036) in comparison to placebo. Mean cross sectional areas of the nasal cavity were reduced to a lesser extent after treatment with ectoine (‒0.020 ± 0.022) than with placebo (‒0.047 ± 0.029). The current study also demonstrated a very good safety profile of ectoine treatment. Few AEs with comparable numbers in both treatment groups were reported during the study, which were mild in severity and resolved without medical treatment.ConclusionThe study suggests that ectoine is effective in reducing nasal and ocular symptoms associated with ARC. Being a natural, bacteria derived stress protection molecule functioning by a physical mode of action, it therefore represents an alternative nonpharmacological treatment option.

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

The environmental exposure chamber (EEC) model mimics naturalistic airborne allergen exposure that patients would encounter in their everyday lives. It allows for the exposure of subjects to a steady and consistent levels of allergen in a controlled environment for repeated exposure days, allowing for reproducibility of data over successive studies. [1 & 2] The aim of this study was to examine the correlation between Total Symptom Scores (TSS) recorded by grass-allergic subjects in the field and their TSS evoked by allergen exposure in the EEC. A total of 149 subjects were screened for grass allergy using skin prick test and serum IgE. Eligible subjects were exposed to airborne grass pollen in the EEC for 3-hours, and recorded their TSS every 30 minutes. The same subjects reported their daily at-home TSS for 6-days prior to peak pollen day, their perception of pollen exposure, and their estimated time spent outdoors using an e-diary. Correlation analysis was performed to investigate the relationship between data gathered in the EEC and in the field diaries. Average TSS for the same subjects who reported no exposure in the field was 9.04 compared to 19.74 in the EEC and showed no correlation (r=0.218, p=0.274). Whereas subjects who reported daily outdoor exposure of 0-3 hours had the strongest correlation (r=0.616, p<0.0001) between field and EEC. Higher TSS was reported by those exposed ≥8 hours daily (18.50 field vs 20.37 EEC). A significant positive correlation (r= 0.5726, p<0.0001) was also observed in subjects who spent 4-7 hours outside. The EEC represents a promising tool to enhance the reliability and comparability of clinical data by controlling confounding variables that are inherent to traditional field-based trials. Many factors should be considered when evaluating the relationship between allergy symptoms in EEC versus field. Specifically, the amount of time subjects spend outdoors and their perceptions of allergen exposure are important considerations that show the EEC can be used to approximate everyday pollen exposures in clinical trials.

Characterization of self-reported pollen food syndrome (PFS) in birch and oak allergic subjects exposed to oak pollen in an environmental exposure chamber (EEC) in Canada

Characterization of self-reported pollen food syndrome (PFS) in birch and oak allergic subjects exposed to oak pollen in an environmental exposure chamber (EEC) in Canada

Effect of air cleaners on early and late asthmatic response in asthmatic subjects sensitized to cat in ALYATEC’s environmental exposure chamber (EEC)

Effect of air cleaners on early and late asthmatic response in asthmatic subjects sensitized to cat in ALYATEC’s environmental exposure chamber (EEC)

Utility of Environmental Exposure Unit Challenge Protocols for the Study of Allergic Rhinitis Therapies.

This paper explores how the Environmental Exposure Unit (EEU) experimental model can be used to further our understanding of pharmacotherapies and immunotherapies for the treatment of allergic rhinitis (AR). EEUs are used increasingly for the study of combination therapies, immunotherapies, and novel AR treatments. A combined antihistamine/corticosteroid nasal spray formulation was seen to have a faster onset of action relative to the therapies individually in the Environmental Exposure Chamber. House dust mite sublingual immunotherapy tablets are both safe and efficacious as evaluated by the Vienna Challenge Chamber. The Kingston EEU found that a novel peptide-based immunotherapy approach to be effective in reducing grass pollen-induced AR. Lastly, nasal filters were determined to reduce seasonal AR symptoms, given out-of-season in the Denmark Environmental Exposure Unit. EEUs are controlled, replicable models that provide valuable insight into the efficacy, onset and duration of action, and dose-related impacts of AR therapeutics, with direct clinical relevance.

Does Air Filtration Work for Cat Allergen Exposure?

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. 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. 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.

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

The direct-instillation nasal allergen challenge (NAC) and the environmental exposure chamber (EEC) are 2 methods of conducting controlled allergen provocations. The clinical and biological comparability of these methods has not been thoroughly investigated. We sought to compare clinical and immunologic responses to cat allergen in NAC versus EEC. Twenty-four participants were randomized to receive either NAC followed by a 2-day challenge in an EEC or a 2-day challenge in an EEC followed by NAC. Challenges were separated by 28-day washout periods. We measured total nasal symptom scores, peak nasal inspiratory flow, nasal (0-8 hours) and serum cytokines, serum antibodies, peripheral blood antigen-specific T lymphocytes, and gene expression in nasal scrapings. The primary outcome was the total nasal symptom score area under the curve for the first 3 hours after allergen exposure in NAC or after initiation of exposure in EEC. Both challenges increased IL-5 and IL-13 in nasal fluids and serum and resulted in altered nasal cell expression of gene modules related to mucosal biology and transcriptional regulation. Changes in gene modules, more so than cytokine measurements, showed significant associations with total nasal symptom score and peak nasal inspiratory flow. Overall, EEC exposure generated larger responses and more early terminations compared with NAC. Although the 2 challenges did not correlate in symptom magnitude or temporality, striking correlations were observed in cytokine levels. Although clinical outcomes of NAC and EEC were temporally different and nonequivalent in magnitude, immunologic responses were similar. Selection of a particular allergen challenge method should depend on considerations of study objectives and cost.