Vienna Challenge Chamber Research Articles

Reconsider the Art of Allergen Immunotherapy

This symposium took place during the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress, held in Prague, Czechia, in July 2022. Stephanie Dramburg, Medical Doctor at Charité Universitätsmedizin, Berlin, Germany, explained that the traditional diagnostic work-up for allergic rhinoconjunctivitis (AR) comprises retrospective clinical history and allergen exposure assessment, extract-based diagnostics, component-resolved diagnostics (CRD), which enables markers of genuine sensitisation to be distinguished from markers of cross-reactivity, and confirmation of clinical relevance. She highlighted that molecular IgE assessment supports the diagnostic work-up and personalised risk assessment in complex cases and that confirmation of clinical relevance of IgE results is key. Furthermore, broadening of a serum IgE response is indicative of ‘molecular spreading’. Dramburg considered that digital technologies have the potential to enhance medical decisions at the point-of-care via targeted patient information, guideline- and evidence-based clinical knowledge, and prospectively collected patient- and sensor-generated data. Marek Jutel, Medical Professor at Wroclaw Medical University, Poland, and the ALL-MED Medical Research Institute, Wroclaw, Poland, described that patients with allergies show different clinical pictures due to differing sensitisation profiles assessed at the molecular level. He noted that patients with allergies react differently to different allergen doses and allergen immunotherapy (AIT) preparations, and minor/intermediate allergens are necessary, in addition to major allergens, for optimal clinical efficacy. Jutel described that allergens that are decisive for AIT efficacy are defined in grass pollen but are not yet determined for other allergen sources such as birch and house dust mite (HDM). Petra Zieglmayer, Medical Professor at Karl Landsteiner University, Krems, Austria, and Head of Vienna Challenge Chamber, Austria, discussed that patients with allergies show complex molecular sensitisation profiles and that extract preparations from different manufacturers vary in terms of allergen composition, with major and intermediate allergens not always detectable. She clarified that optimal efficacy of AIT may only be expected from preparations containing all relevant allergen components in sufficient amounts. Zieglmayer proposed that the target should be to find a match between the patient molecular sensitisation profile and the allergen preparation and that this can be achieved.

Reconsider the Art of Allergen Immunotherapy

This symposium took place during the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress, held in Prague, Czechia, in July 2022. Stephanie Dramburg, Medical Doctor at Charité Universitätsmedizin, Berlin, Germany, explained that the traditional diagnostic work-up for allergic rhinoconjunctivitis (AR) comprises retrospective clinical history and allergen exposure assessment, extract-based diagnostics, component-resolved diagnostics (CRD), which enables markers of genuine sensitisation to be distinguished from markers of cross-reactivity, and confirmation of clinical relevance. She highlighted that molecular IgE assessment supports the diagnostic work-up and personalised risk assessment in complex cases and that confirmation of clinical relevance of IgE results is key. Furthermore, broadening of a serum IgE response is indicative of ‘molecular spreading’. Dramburg considered that digital technologies have the potential to enhance medical decisions at the point-of-care via targeted patient information, guideline- and evidence-based clinical knowledge, and prospectively collected patient- and sensor-generated data. Marek Jutel, Medical Professor at Wroclaw Medical University, Poland, and the ALL-MED Medical Research Institute, Wroclaw, Poland, described that patients with allergies show different clinical pictures due to differing sensitisation profiles assessed at the molecular level. He noted that patients with allergies react differently to different allergen doses and allergen immunotherapy (AIT) preparations, and minor/intermediate allergens are necessary, in addition to major allergens, for optimal clinical efficacy. Jutel described that allergens that are decisive for AIT efficacy are defined in grass pollen but are not yet determined for other allergen sources such as birch and house dust mite (HDM). Petra Zieglmayer, Medical Professor at Karl Landsteiner University, Krems, Austria, and Head of Vienna Challenge Chamber, Austria, discussed that patients with allergies show complex molecular sensitisation profiles and that extract preparations from different manufacturers vary in terms of allergen composition, with major and intermediate allergens not always detectable. She clarified that optimal efficacy of AIT may only be expected from preparations containing all relevant allergen components in sufficient amounts. Zieglmayer proposed that the target should be to find a match between the patient molecular sensitisation profile and the allergen preparation and that this can be achieved.

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.

A novel formulation of budesonide nasal spray (Budesolv 10) potentiates clinical performance in grass pollen allergic patients

Abstract Objective Purpose of this DBPC study was to evaluate onset of action and non-inferiority of a novel low dose aqueous solution of Budesonide (“Budesolv 10μg”) to Rhinocort® aqua 64μg (RA) in adult grass pollen allergic patients. Methods Budesonide, a poorly water-soluble corticosteroid, currently marketed as suspension, was reformulated to enhance solubility and local concentration on the target mucosa. Subjects received Budesolv, the market comparator RA and placebo once daily for 8 days. Allergic symptoms were induced by 6h grass pollen challenges in the Vienna Challenge Chamber at days 1 and 8 of each treatment period. First dose was applied after 1:45h to evaluate onset of action of either treatment. Nasal, ocular, asthma symptoms and objective measures of nasal secretion and nasal obstruction were evaluated. A 95% confidence interval (CI) was calculated for difference in means between active treatments. Non-inferiority was stated if the upper limit of the CI did not exceed 115% of the reference. Onset of action was defined as first time point when the difference in nasal symptoms change from baseline between active treatment and placebo was p<0.05. Results 75 patients concluded the study per protocol. The primary endpoint (TNSS; sum of obstruction, itch, sneeze and rhinorrhoea) was met proving non-inferiority of Budesolv compared to RA. A significant difference between Budesolv and placebo was shown for TNSS 2.45 h and for total asthma score 2 h after first dose. On day 8 Budesolv 10μg was significantly better than placebo for all parameters evaluated. Conclusion Non-inferiority of Budesolv compared to Rhinocort® was shown on day 8 of treatment. Early onset of action within 3h after first dose was evident for Budesolv only.

Cetirizine inhibits gender-specific blood cell dynamics upon allergen contact in allergic rhinitis

IgE-mediated inflammatory responses upon allergen contact in allergic rhinitis (AR) are associated with rapid alterations of circulating blood cell numbers detectable in a complete blood count (CBC). Aim of this study was to evaluate whether intake of antihistamines may modulate allergen-induced CBC dynamics in male and female patients.A total of N = 112 specific allergen challenges were performed in otherwise healthy AR subjects. Seventy-two (n = 72) subjects received placebo and forty (n = 40) received cetirizine (H1-receptor antagonist) per os prior to allergen exposure in a randomized, double-blind trial at the Vienna Challenge Chamber (VCC); a subgroup of twenty-five (n = 25) subjects received cetirizine and placebo on different study days (parallel group). Blood samples and symptom scores were taken at baseline and immediately after 6 h of airway challenge simulating ambient allergen contact.Female sex was associated with a pronounced circulating monocyte increase (p < .01) and male sex with an eosinophil decrease (p < .05) in the placebo group, but not in cetirizine treated subjects. The significant increase in segmented neutrophils (p < .001) and decrease in circulating erythrocytes (p < .01) upon allergen challenge was less prominent after cetirizine intake in both sexes. A more prominent thrombocyte increase in female subjects (p < .05) was noted upon allergen exposure, regardless of prior cetirizine intake.Cetirizine inhibited the mobilization of neutrophils, lymphocytes and decline in erythrocyte numbers, but did not affect thrombocyte increase upon allergen challenge. It further diminished gender-specific blood cell dynamics. Overall, as reflected in a simple CBC, cetirizine critically diminished immediate and late innate immune responses subsequent to allergen exposure.

Underestimation of house dust mite–specific IgE with extract-based ImmunoCAPs compared with molecular ImmunoCAPs

Underestimation of house dust mite–specific IgE with extract-based ImmunoCAPs compared with molecular ImmunoCAPs

Sublingual house dust mite immunotherapy has no impact on decrease of circulating erythrocytes upon airway allergen challenge in allergic rhinitis

House dust mite (HDM) allergy is a predominant cause for perennial allergic rhinitis (AR) in Europe. We recently reported that circulating erythrocyte numbers decrease after airway allergen challenge in a murine asthma model and in grass-pollen sensitized AR subjects. Consequently, we aimed to evaluate these findings in HDM sensitized AR subjects and the influence of preceding allergen immunotherapy. Seventy-seven (age 26.8 ± 7.3 years; 54.5% female) HDM-allergic rhinitis subjects previously enrolled in a randomized, monocentric sublingual immunotherapy (SLIT) trial at the Vienna Challenge Chamber (VCC) were included. Subjects had either received placebo (n = 22), low-dose HDM (n = 29) or high-dose HDM specific sublingual immunotherapy (n = 26) daily for 24 weeks. Blood sampling was performed before and after 6 hours of HDM allergen exposure. Overall, specific airway allergen challenge resulted in a significant decrease in circulating erythrocytes and hematocrit (p < 0.001), and elevation of leukocytes (p < 0.001), particularly segmented neutrophils (p < 0.001). Gender had no significant effect on the observed changes in circulating blood cells. Erythrocytes decreased and neutrophil counts increased significantly after airway allergen challenge regardless of preceding immunotherapy. These findings imply a rapid systemic mobilization of neutrophils occurring within immediate type hypersensitivity response upon a specific allergen challenge, which is possibly inversely linked with the erythrocyte numbers.

Randomized phase 1 study of the phosphatidylinositol 3-kinase δ inhibitor idelalisib in patients with allergic rhinitis

Phosphatidylinositol 3-kinase p110δ isoform (PI3K p110δ) activity is essential for mast cell activation, suggesting that inhibition of PI3K p110δ might be useful in treating allergic diseases. We sought to determine the effect of the PI3K p110δ-selective inhibitor idelalisib on allergic responses. This phase 1 randomized, double-blind, placebo-controlled, 2-period crossover study was conducted with the Vienna Challenge Chamber. Grass pollen-induced allergic symptoms were documented during screening. Eligible subjects received idelalisib (100mg twice daily) or placebo for 7days, with allergen challenge on day 7. After a 2-week washout period, subjects received the alternate treatment and repeated allergen challenge. Study measures included safety, nasal and nonnasal symptoms, nasal airflow, nasal secretions, basophil activation, and plasma cytokine levels. Forty-one patients with allergic rhinitis received idelalisib/placebo (n=21) or placebo/idelalisib (n=20). Idelalisib treatment was well tolerated. Mean total nasal symptom scores were lower during the combined idelalisib treatment periods compared with placebo (treatment difference [idelalisib-placebo], -1.78; 95% CI, -2.53 to -1.03; P<.001). Statistically significant differences were also observed for the combined treatment periods for total symptom scores, nasal airflow, nasal secretion weight, and nasal congestion scores. The percentage of exvivo-activated basophils (CD63(+)/CCR3(+) cells; after stimulation with grass pollen) was substantially lower for idelalisib-treated compared with placebo-treated subjects. Plasma CCL17 and CCL22 levels were reduced after idelalisib treatment. Idelalisib treatment was well tolerated in patients with allergic rhinitis and appears to reduce allergic responses clinically and immunologically after an environmental allergen challenge.

The improved efficacy of a fixed-dose combination of fluticasone furoate and levocabastine relative to the individual components in the treatment of allergic rhinitis.

Allergic rhinitis (AR) is a common chronic disease, which has significant detrimental effect on well-being and quality of life as well as substantial socio-economic impact. Combination pharmacotherapy is utilized by 40-50% of patients to treat their symptoms. To compare the effects of intranasal fluticasone furoate (FF)/levocabastine (LEVO) fixed-dose combination (FDC) with each component alone on allergen-induced nasal and ocular symptoms. A randomized, double-blind, placebo-controlled, three-way, incomplete block, cross-over, proof-of-concept study in 71 patients with AR, evaluated FF 100 μg, LEVO 200 μg and FDC (FF 100/LEVO 200 μg), once daily via intranasal spray for 8 days. On days 1 and 8, total nasal symptom score (TNSS) and total ocular symptom score (TOSS) were assessed every 15 min during a 4-h allergen exposure in the Vienna Challenge Chamber. The primary endpoint was Day 8 weighted mean TNSS. After 8 days, FDC resulted in both statistically and clinically significant reductions in mean TNSS compared with FF and LEVO alone [adjusted mean differences (95% CI): FDC vs. FF: -2.26 (-2.90, -1.62); FDC vs. LEVO: -2.57 (-3.21, -1.93)]. All active treatments were significantly superior to placebo [adjusted mean difference (95% CI) from placebo: FDC: -4.1 (-4.86, -3.34); FF: -1.84 (-2.66, -1.03); LEVO: -1.53 (-2.34, -0.72)]. Onset of action was rapid following FDC and LEVO treatment with an approximate two unit reduction in mean TNSS from pre-dose levels by 30 min and 1 h. Mean TOSS was also reduced following all active treatments relative to placebo (range 0.6-0.8 unit reduction). All treatments were equally well tolerated. These results suggest that once daily FF/LEVO FDC could provide a clinical therapeutic advantage to existing standard monotherapies in the treatment of moderate-to-severe AR, and support progression to evaluation in larger phase III clinical studies.

Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research.

The aim of this study is to review advances in basic and clinical allergic rhinitis (AR) research over the past decade that have been conducted using controlled allergen challenge facility (CACF) models of allergen challenge. Databases, including PubMed, Medline, and Web of Science were searched for articles employing an ambient pollen exposure in a controlled facility to study AR, published between 2004 and the present date, using the terms as follows: CACF, Environmental Exposure Unit (EEU), Vienna Challenge Chamber (VCC), Fraunhofer Institute Environmental Challenge Chamber, Atlanta Allergen Exposure Unit, Biogenics Research Chamber, Allergen BioCube, Chiba and Osaka Environmental Challenge Chamber, exposure unit, challenge chamber, or environmental exposure chamber. Articles were then selected for relevance to the goals of the present review, including important contributions toward clinical and/or basic science allergy research. CACFs offer sensitive, specific, and reproducible methodology for allergen challenge. They have been employed since the 1980s and offer distinct advantages over traditional in-season multicentre trials when evaluating new treatments for AR. They have provided clinically applicable efficacy and pharmacologic information about important allergy medications, including antihistamines, decongestants, antileukotrienes, immunotherapies, and nasal steroids. CACF models have also contributed to basic science and novel/experimental therapy research. To date, no direct studies have been conducted comparing outcomes from one CACF to another. Over the past decade, CACF models have played an essential role in investigating the pathophysiology of AR and evaluating new therapies. The future opportunities for this model continue to expand.

Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber

The magnitude of effect of sublingual immunotherapy for house dust mite (HDM)-induced allergic rhinitis with or without conjunctivitis is uncertain, partly because there are few well-controlled trials with well-defined doses. We sought to determine the dose-related efficacy and onset of action of the HDM sublingual immunotherapy tablet MK-8237 (Merck/ALK-Abelló) using the Vienna Challenge Chamber. In this randomized, double-blind, single-site trial, adults with HDM-induced allergic rhinitis with or without conjunctivitis and with or without asthma (n= 124) received 12 developmental units (DU) of MK-8237, 6 DU of MK-8237, or placebo daily for 24 weeks. Subjects underwent 6-hour exposure challenges at screening and weeks 8, 16, and 24. The total nasal symptom score (TNSS) during chamber challenge at week 24 was the primary end point. The TNSS was the sum of 4 nasal symptom scores (maximum= 12). Total ocular symptom scores (TOSSs; 2 symptoms; maximum= 6) and total symptom scores (TSSs; TSS= TNSS plus TOSS; maximum= 18) were secondary end points. Dose- and time-dependent improvements with MK-8237 versus placebo were observed. At week 24, TNSS improvement relative to placebo was 48.6% (95% CI, 35.3% to 60.2%) with 12 DU of MK-8237 and 26.6% (95% CI, 11.2% to 39.6%) with 6 DU of MK-8237. Statistically significant improvements for TNSSs were also observed at weeks 8 (12 DU of MK-8237) and 16 (6 and 12 DU of MK-8237) and for TOSSs and TSSs by both doses at week 24. MK-8237 was well tolerated. No investigator-assessed anaphylactic allergic reactions or reactions requiring epinephrine were observed. MK-8237, 12 DU, reduced nasal and ocular symptoms and exceeded World Allergy Organization-established clinical efficacy criteria (≥20% improvement vs placebo). The onset of action for 12 DU of MK-8237 was week8.MK-8237, 12 DU, is appropriate for further evaluation to determine the magnitude of effect in an uncontrolled allergenexposure environment.

Peripheral Erythrocytes Decrease upon Specific Respiratory Challenge with Grass Pollen Allergen in Sensitized Mice and in Human Subjects

Background and AimsSpecific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i) sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii) grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC).Methods and ResultsBALB/c mice (n = 20) were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10) or the non-specific antigen ovalbumin (OVA) (n = 10). A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42) at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites.ConclusionOur data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens. A rapid recruitment of erythrocytes to the lungs to compensate for hypoxia is a possible explanation for these findings.

The effects of a TRPV1 antagonist, SB-705498, in the treatment of seasonal allergic rhinitis

Current pharmacotherapy for allergic rhinitis (AR) does not totally ameliorate all symptoms for all patients. Residual symptoms could be due to nasal neuronal hyperresponsiveness caused by stimulation of the ion channel transient receptor potential vanilloid 1 (TRPV1). SB-705498 is a TRPV1 antagonist that has been developed in an intranasal formulation for treatment of AR. This randomized, double-blind, 3-way incomplete block crossover study evaluated the effects of 8 days treatment with SB-705498 12 mg alone, SB-705498 12 mg plus fluticasone propionate 200 μg (FP), FP 200 μg alone or placebo on allergen-induced symptoms in 70 patients with AR. The primary endpoint was total nasal symptom score (TNSS), expressed as mean over 4 hours or maximum TNSS during allergen challenge in the Vienna Challenge Chamber on 8th day of treatment. At the end of treatment, there were no differences in allergen-induced mean TNSS between SB-705498 alone and placebo or between SB-705498 plus FP and FP alone. Treatment with FP and SB-705498 plus FP resulted in a significant decrease in TNSS vs. placebo. Mean (90% CI) treatment differences in TNSS over 0 - 4 hours were: SB-705498 - placebo: -0.2 (-0.9, 0.4); SB-705498 plus FP - FP: 0.7 (0.2, 1.2); FP - placebo: -2.9 (-3.4, -2.5); SB-705498 plus FP - placebo: -2.3 (-2.8, -1.8). SB-705498 had no impact on diary card symptoms, nasal airflow or Rhinoconjunctivitis Quality of Life Questionnaire scores. SB-705498 was well tolerated and pharmacokinetics exposure results supported the dosing regimen. SB-705498 12 mg for 8 days did not alleviate the allergen-induced symptoms of AR, or provide additional relief of symptoms when in combination with FP. Despite engagement of the TRPV1 receptor there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.

Onset of action of loratadine/montelukast in seasonal allergic rhinitis patients exposed to grass pollen

Given the impact of allergic rhinitis (AR) on quality of life, it is important that AR medications have rapid onset of symptom relief. The objective of this study was to determine the onset of action of loratadine (CAS 79794-75-5)/montelukast (CAS 151767-02-1) 10 mg/10 mg (L/M) versus placebo in seasonal AR (SAR) subjects. In this single-center, double-blind, crossover study, subjects with SAR and confirmed sensitivity to grass pollen received single doses of L/M or placebo following exposure to grass pollen in the Vienna Challenge Chamber. Subjects recorded symptoms at 15-min intervals during the first 2 h post dose and at 30-min intervals during the next 2 h. After a 14-day washout, the subjects crossed over to the other treatment. The primary endpoint was onset of action of L/M, defined as the first time point at which the mean change from baseline in total symptom score became and remained significantly different with L/M versus placebo. Secondary endpoints included nasal congestion score and rhinomanometry findings. Onset of action with L/M for total symptom score was 1 h, 45 min (P < 0.01 vs placebo). Significant improvements in subject-assessed nasal congestion scores (P < 0.01) and rhinomanometry (P = 0.036) were noted with L/M as compared with placebo. Overall, L/M was well tolerated. In conclusion, L/M demonstrated rapid onset for broad symptom relief, including nasal congestion, in subjects with SAR.

VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis

Introduction: Allergic rhinitis significantly impacts quality of life and current treatments are frequently unsatisfying. VTX-1463 is a potent, selective, Toll-like receptor (TLR) 8 agonist administered weekly via the intranasal route without concomitant administration of allergen for the treatment of allergic rhinitis.Areas covered: The rationale for TLR8 as a therapeutic target in allergic disease is summarized. The potency of VTX-1463 for TLR8 is outlined, and preclinical efficacy data from a ragweed-sensitized beagle dog model of allergic rhinitis are reviewed. Results of three randomized, double-blind, placebo-controlled trials with VTX-1463 are also reviewed: (i) a first-in-man study in healthy volunteers, (ii) an allergen challenge study in atopic individuals out of pollen seasons and (iii) an allergen challenge study in atopic individuals during season.Expert opinion: Two or four weekly pretreatments with VTX-1463 in subjects with grass pollen allergies provided statistically significant improvement in nasal symptoms, as measured by total nasal symptom score (TNSS) and active anterior rhinomanometry (AAR), while subjects were exposed to grass pollen in the Vienna Challenge Chamber (VCC). Improvement in nasal secretion weights and ocular symptom scores was also observed. VTX-1463 is a promising new agent for the treatment of seasonal, and potentially perennial, allergic rhinitis.

Intranasal Toll-like Receptor 8 Agonist (VTX-1463) Significantly Improves Symptoms of Allergic Rhinitis in a Randomized, Placebo-Controlled Trial

RATIONALE: Toll-like receptors (TLRs) have been shown to modulate allergic immune responses. The safety and efficacy of VTX-1463_a novel, small-molecule, TLR8 agonist given once weekly intranasally_was assessed in allergic rhinitis (AR) subjects exposed to allergen in the Vienna Challenge Chamber (VCC).

The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber

This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber

Studies on the efficacy of phenylephrine in the treatment of nasal congestion have yielded inconsistent results, notwithstanding its approval for this indication. To evaluate and compare the decongestant effect of a single dose of phenylephrine to placebo and pseudoephedrine in patients with seasonal allergic rhinitis. This randomized, placebo-controlled, 3-way crossover study evaluated patient-scored nasal congestion, peak nasal inspiratory flow, and rhinomanometry at more than 6 hours in 39 grass-sensitive patients exposed to grass pollen in the Vienna Challenge Chamber. Patients were dosed with immediate-release formulations of phenylephrine, 12 mg, pseudoephedrine, 60 mg, as a control, or placebo. Phenylephrine was not significantly different from placebo in the primary end point, mean change in nasal congestion score at more than 6 hours (P = .56), whereas pseudoephedrine was significantly more effective than both placebo (P < .01) and phenylephrine (P = .01). Phase 1 results showed a difference between phenylephrine and placebo that was 64% of the difference between pseudoephedrine and placebo, substantially greater than the 17% difference observed for all phases. Carryover bias due to patient recall of the pseudoephedrine effect may have influenced these results. Rhinomanometry and peak nasal inspiratory flow results were consistent with these data. Neither phenylephrine nor pseudoephedrine had an effect on the nonnasal symptoms. No adverse events were reported in this study. During a 6-hour observation period, a single dose of pseudoephedrine but not phenylephrine resulted in significant improvement in measures of nasal congestion. Neither phenylephrine nor pseudoephedrine had an effect on nonnasal symptoms.

Fluticasone furoate versus placebo in symptoms of grass-pollen allergic rhinitis induced by exposure in the Vienna Challenge Chamber

ABSTRACTObjective: The Vienna Challenge Chamber (VCC) offers a controlled and controllable paradigm in which to reproducibly evaluate the efficacy of anti-allergic treatment. The aim of this study was to assess the efficacy of the novel intranasal corticosteroid fluticasone furoate (FF) in the VCC.Methods: The single-centre, randomised, double-blind, placebo-controlled, two-period crossover study was conducted in 59 adult males with grass pollen allergic rhinitis (AR). Patients received either Fluticasone furoate 200 mcg once-daily, or placebo intranasally for 8 days. AR symptoms were induced during 4-hour allergen challenges with grass pollen in the VCC at the end of each 8-day treatment period. A first challenge was conducted at 1–5 hours post-dose, followed by a second challenge at 22–26 hours post-dose. The primary endpoint was total nasal symptom score (TNSS; sum of itch, sneeze, rhinorrhoea, obstruction symptoms assessed on a categorical scale of 0–3) weighted mean over 2–5 hours post-dose. Secondary endpoints included: TNSS weighted mean over 23–26 hours post-dose and global symptom score, eye symptom score, nasal secretions and nasal airflow weighted means over 2–5 and 23–26 hours post-dose.Results: Fluticasone furoate showed consistent attenuation of AR symptoms in both the early and late challenges. Compared with placebo, weighted mean of TNSS was reduced on average by 4.14 point-scores at 2–5 hours post-dose and 3.63 point scores at 23–26 hours post-dose. These positive effects were also seen across all secondary endpoints.Conclusion: An 8-day treatment course of intranasal FF 200 mcg given once-daily statistically significantly reduced symptoms of AR including associated eye symptoms. Statistical significance was declared where the relevant two-sided 95 % confidence interval did not contain zero. This positive effect was sustained over 24 hours suggesting that fluticasone furoate could be efficacious as a once daily steroid.

Effects of the Novel Intranasal Glucocorticosteroid Gw685698 (200μG Once-daily) on Seasonal Allergic Rhinitis (sar) Symptoms Induced in the Vienna Challenge Chamber Model (vcc)

Effects of the Novel Intranasal Glucocorticosteroid Gw685698 (200μG Once-daily) on Seasonal Allergic Rhinitis (sar) Symptoms Induced in the Vienna Challenge Chamber Model (vcc)