Environmental Challenge Chamber Research Articles

Evaluation of shoseiryuto for seasonal allergic rhinitis, using an environmental challenge chamber

BackgroundComplementary and alternative medicine, including Japanese traditional medicine (JTM), has been used for various allergic diseases, but the evidence is limited. Shoseiryuto (Xiao-Qing-Long-Tang), one of the representative JTM drugs, is frequently used to treat allergic rhinitis (AR). However, its efficacy for seasonal AR has not been fully established. Using an Environmental challenge chamber (ECC), we evaluated the therapeutic effects of shoseiryuto on AR induced by Japanese cedar pollen (JCP). MethodsA placebo-controlled double-blind crossover study with shoseiryuto was conducted using the ECC. The shoseiryuto or placebo was orally administered from 2 weeks before the exposure test. The pollen exposure test was conducted for 3 h, and the pollen concentration was set at 8000 pollen/m3. The primary endpoint of the study was the total nasal symptom score (TNSS) during pollen exposure. A physician certified by the Japanese Society of Oriental Medicine as a specialist checked each participant's “pattern”, a comprehensive expression of signs obtained from individual patients' subjective symptoms and other personal findings. Blood samples collected just before the first pollen exposure were stimulated with cedar antigens and used for immunological studies. ResultsThe results of the 46 participants were analyzed, and no significant side effects were detected. There was no significant difference in TNSS during pollen exposure for 3 h in the ECC between the shoseiryuto and placebo groups. However, some symptoms were improved in the shoseiryuto group after leaving the ECC. There was no significant correlation between the “fluid retention pattern” and TNSS. In immunological studies, shoseiryuto did not inhibit Th2-type cytokine production and mRNA expression. ConclusionsOral administration of shoseiryuto from 2 weeks before pollen exposure did not prevent or inhibit immediate symptoms of AR induced by JCP in the ECC. Further study is needed to reevaluate the shoseiryuto specific “pattern” in JTM.

Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study

Background: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. Objective: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. Methods: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m³. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. Results: The difference in TNSS from placebo was –2.42 (p < 0.0001) with levocetirizine and –1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. Conclusion: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. Clinical Trial Registration number: UMIN ID: UMIN000029653.

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

A VALIDATION STUDY OF THE IMPROVED PRODUCT FOR MEASURING JAPANESE CYPRESS POLLEN-SPECIFIC IgE (THERMO SCIENTIFIC™ ImmunoCAP™ ImmunoCAP JAPANESE CYPRESS POLLEN-SPECIFIC IgE)

Japanese cypress pollen is a major causative allergen of seasonal allergic rhinitis in Japan. Although ImmunoCAP-specific immunoglobulin E (IgE) reagent Japanese cypress pollen has been widely used as a diagnostic aid, its sensitivity requires enhancement. This study evaluated an improved version of this reagent. Serum samples from 61 subjects who underwent Japanese cypress pollen exposure testing in an environmental challenge chamber in Chiba University were assessed using the conventional ImmunoCAPspecific IgE Japanese cypress pollen product and the improved product. In addition, specific IgE for Cha o 1 and Cha o 2, the primary allergen components of Japanese cypress pollen, was evaluated and their reactivity to specific IgE was compared between the conventional and improved products. The antibody titer of the improved product was approximately 1.8-fold that of the conventional product. In addition, higher correlations with Cha o 1 and Cha o 2 were observed for the improved product than for the conventional product. The clinical sensitivity (≥class 2) in 56 exposure test-positive subjects was better for the improved product (80.4%) than for the conventional product (71.4%). An improvement of the ImmunoCAP-specific IgE reagent Japanese cypress pollen resulted in enhanced Japanese cypress pollen-specific IgE sensitivity. The primary reason for this appeared to be an improved Cha o 1- and Cha o 2-specific IgE detectability.

Clinical validation of a house dust mite environmental challenge chamber model

Clinical validation of a house dust mite environmental challenge chamber model

Standardized quality house dust mite sublingual tablets (Acarizax®): a guide to their use as sublingual allergy immunotherapy in Europe

Standardized quality (SQ) house dust mite (HDM) allergen extract tablets (Acarizax®) are a valuable option for sublingual allergy immunotherapy (SLIT) in adults with confirmed HDM-induced allergic rhinitis or allergic asthma. In placebo-controlled natural-field and environmental exposure challenge chamber trials, Acarizax® reduced the symptoms of allergic rhinitis in adults with HDM-induced allergic rhinitis (± asthma) and reduced the risk of asthma exacerbations in adults with HDM-induced allergic asthma. A systemic antibody response to HDM allergens has been observed within 4 weeks of initiating SLIT with Acarizax®. Precautions should be followed to minimize the risk of systemic and local allergic reactions inherent to SLIT.

Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber

BackgroundImmediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis. ObjectiveTo examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC). MethodsFifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m3 for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored. ResultsThe severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased. ConclusionVarious mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.

House dust mite sublingual tablets (Actair®): a guide to their use as allergy immunotherapy for house dust mite-induced allergic rhinitis

House dust mite (HDM) allergen extract sublingual tablets (Actair®) are a valuable option to reduce allergy symptoms in patients with HDM-induced allergic rhinitis. Allergy immunotherapy (AIT) with 300 index of reactivity (IR) Actair® reduced the symptoms of allergic rhinitis in placebo-controlled natural-field and environmental exposure challenge chamber trials. Significant beneficial effects with 300 IR Actair® relative to placebo were shown as early as 2 months after the initiation of treatment, with efficacy being continuously maintained during the rest of the 1-year AIT period, as well as during a subsequent AIT-free year. Precautions should be followed to minimize the risk of systemic and local allergic reactions inherent to AIT.

Characteristics of laryngeal symptoms induced in patients with allergic rhinitis in an environmental challenge chamber

BackgroundPeople with allergic rhinitis often have laryngeal symptoms (LSs) in addition to nasal symptoms during the pollen-scattering season. ObjectiveTo clarify the characteristics of the LSs induced by pollen exposure using an environmental challenge chamber. MethodsCypress pollen exposure using an environmental challenge chamber for 25 participants with cypress pollen–induced allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study courses: namely, pollen exposure under normal nasal breathing and pollen or sham pollen exposure with nasal blockage, which eliminated any allergic reactions in the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal examinations and physiologic lung tests were also conducted. ResultsVarious LSs were reported, and these LSs were significantly elevated during pollen exposure and even under sham exposure with artificial nasal blockage. The pollen exposure with artificial nasal blockage exaggerated the LSs in 32% of the participants and also increased the serum ECP levels. The serum ECP levels did not change after sham exposure. The findings of both laryngeal examinations and lung tests failed to reveal any significant changes. ConclusionNasal obstruction could induce significant LSs even without pollen exposure. LSs were enhanced by pollen exposure and allergic reactions in the larynx could thus be involved in this enhancement. Trial Registrationclinicaltrials.gov Identifier: UMIN000015667.

Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber

It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD). We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design. Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m(3) of Dactylis glomerata pollen or clean air. The severity of AD was assessed at each study visit up to 5 days after challenge by (objective) scoring of AD (SCORAD). Additionally, air-exposed and non-air-exposed skin areas were each scored using local SCORAD scoring and investigator global assessments. Levels of a series of serum cytokines and chemokines were determined by using a Luminex-based immunoassay. The primary end point of the study was the change in objective SCORAD scores between prechallenge and postchallenge values. Exposure to grass pollen induced a significant worsening of AD. A pronounced eczema flare-up of air-exposed rather than covered skin areas occurred. In grass pollen-exposed subjects a significantly higher increase in CCL17, CCL22, and IL-4 serum levels was observed. This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms.

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.

Characteristics of the Chiba Environmental Challenge Chamber

An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.

Poster 1007: Universal allergen particle generation for inhaled allergen challenges in the fraunhofer environmental challenge chamber (ECC)

Background Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might overcome aforementioned limitations. However, airborne allergens such as house dust mite (HDM) or cat allergen are not available as standardized source material with distinct particle size. Therefore, we developed a method for universal allergen particle generation and conducted a pilot study to clinically validate this challenge paradigm for house dust mite.

Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis

The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant receptor homologous molecule on T(H)2 cells (CRTH2). We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 μg once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR. In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours. The primary efficacy variable was the total nasal symptom score assessed as the area under the curve (AUC)(0-6h). In total, 146 patients (63.7% male; mean age, 36.1 years) were randomized. The adjusted mean total nasal symptom score AUC(0-6h) was significantly reduced versus placebo with 200 mg of BI 671800 (absolute difference, -0.85; percentage difference, -17%; P = .0026), montelukast (absolute difference, -0.74; percentage difference, -15%; P = .0115), and fluticasone propionate (absolute difference, -1.64; percentage difference, -33%; P < .0001). Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P < .05 for all doses), significantly inhibited nasal inflammatory cytokine levels (IL-4 and eotaxin, P < .05; 200 mg twice daily), and induced a dose-related reduction in ex vivo prostaglandin D2-mediated eosinophil shape change. Two hundred milligrams of BI 671800 twice daily demonstrated efficacy in treating SAR symptoms induced by environmental challenge chamber allergen exposure and had a favorable safety profile.

Randomized Double-Blind Study of Prophylactic Treatment with an Antihistamine for Seasonal Allergic Rhinitis

Background: The efficacy of prophylactic treatment before the start of pollen dispersal for prevention of aggravation of symptoms is unclear. The aim of the present study was to examine the efficacy of prophylactic treatment with an antihistamine for seasonal allergic rhinitis (SAR) using an environmental challenge chamber (ECC). Methods: The study was performed in a randomized double-blind manner with a 3-way crossover design. The subjects were 50 patients with SAR caused by Japanese cedar pollen who were randomized for treatment with levocetirizine hydrochloride 5 mg (Xyzal®) or placebo as follows: administration of placebo for 8 days (treatment A), single administration of levocetirizine on day 8 after placebo for 7 days (treatment B) or administration of levocetirizine for 8 days (treatment C). Efficacy in each treatment arm was evaluated based on cedar pollen exposure for 3 h on day 9 in an ECC, following 1-hour exposure on day 8. The primary endpoint was the total nasal symptom score for 12 h on day 9. Other nasal and ocular symptoms were secondary endpoints. Results: The evaluation was performed in 45 subjects. The total nasal symptom score on day 9 was significantly lower with treatment B compared with treatment A. Treatment C did not show superior efficacy compared with treatment B. Conclusions: Our results suggest that early intervention with levocetirizine soon after onset of symptoms may attenuate these symptoms as effectively as prophylactic treatment before pollen dispersal. These results are important from the perspective of patient convenience and reduction of medical costs.

P154 TRPV1 is not a Target for the Treatment of non-allergic Rhinitis: A Clinical Study

BackgroundTRPV1 is a ligand gated ion channel activated by a range of physiological factors such at Temperature, pH, and osmotic stress. In the nose, the TRPV1-expressing sensory c-fibres are thought...

Comparison of nasal steroid with antihistamine in prophylactic treatment against pollinosis using an environmental challenge chamber

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain_e.jsp).

Pollen starch granules in bronchial inflammation

BackgroundPollen grains with a diameter of more than 10 μm preferentially deposit in the upper airways. Their contribution to lower airway inflammation is unclear. One hypothesis is that lower airway inflammation is mainly caused by allergen containing pollen starch granules, which are released from the pollen grains and can easily enter the peripheral airways because of their smaller size. ObjectiveTo investigate the differential effect of pollen grains and pollen starch granules on nasal symptoms and lower airway inflammation. MethodsIn a 2-period crossover design, 30 patients with allergic rhinitis and mild intermittent asthma underwent 2 allergen challenges on consecutive days in an environmental challenge chamber with either a mixture of pollen grains plus starch granules or starch granules only. End points were the total nasal symptom score (TNSS), nasal secretion weight, nasal flow, spirometry, and exhaled nitric oxide (eNO). ResultsThe presence of pollen grains had a significant and considerable effect on increase in TNSS and secretion weight and on decrease in nasal flow. Starch granules alone only had minimal effects on nasal symptoms. Challenges with starch granules significantly increased eNO. Pollen had no effect on eNO. ConclusionPollen grains cause nasal symptoms but do not augment lower airway inflammation, whereas starch granules trigger lower airway inflammation but hardly induce nasal symptoms.

The Efficacy and Tolerability of Two Novel H1/H3 Receptor Antagonists in Seasonal Allergic Rhinitis

Background: A therapeutic role for histamine H₃ receptor antagonism in allergic rhinitis has been proposed and may be complimentary to the well-known benefits of H₁ receptor antagonism. Combined H₁/H₃ blockade has therefore been investigated as a novel therapeutic approach that may enhance symptom relief, particularly nasal blockage. Methods: Two novel H₁/H₃ dual receptor antagonists were investigated in phase I and II safety and efficacy studies. One molecule (GSK1004723) was designed for intranasal administration as a suspension or solution and the other molecule (GSK835726) for oral administration. In phase I and II studies, both molecules were compared with an active control and/or placebo in randomised studies. In phase II studies, efficacy was assessed in an environmental allergen challenge chamber (ECC). Subjects with seasonal allergic rhinitis were exposed to allergen to induce symptoms. Efficacy and safety was measured over 4, 7 and 20–24 h post-dose. The endpoints included total nasal symptom score and nasal blockage. Results: Intranasal suspension of GSK1004723 and oral GSK835726 were well tolerated. Single-dose intranasal suspensions of GSK1004723 (220, 1,100 µg) failed to demonstrate clinically significant attenuation of symptoms of allergic rhinitis induced in the ECC. Single (10, 50, 100 mg) and 3-day repeat (10 mg) dose oral GSK835726 demonstrated clinically significant attenuation of symptoms in the ECC comparable to cetirizine 10 mg. Three-day repeat dosing of the intranasal solution GSK1004723 1,000 µg also demonstrated a statistically significant attenuation of nasal symptoms, but was less than seen with cetirizine and GSK835726 and caused initial nasal discomfort. Conclusions: Combined H₁/H₃ antagonism did not show differentiation from H₁ antagonism in reducing total nasal symptom score or nasal blockage.

Anti-allergic drug testing in an environmental challenge chamber is suitable both in and out of the relevant pollen season

An environmental challenge chamber (ECC) is a useful tool to expose allergic patients to relevant allergens in a controlled indoor setting and to test anti-allergic treatment. Hitherto, ECC studies with grass pollen are conducted primarily outside of the pollen season to avoid the influence of natural pollen exposure. To investigate whether an established anti-allergic treatment, a combination of cetirizine (CET) and pseudoephedrine (PSE), shows an equivalent treatment effect within and outside of the grass pollen season when tested in an ECC. In a randomized, placebo-controlled, double-blind, four-way crossover study, the effect of a combination of 10 mg CET and 120 mg PSE compared with placebo on nasal symptoms, nasal flow, and nasal secretion was investigated in 70 patients with seasonal allergic rhinitis. Subjects underwent four 6-hour pollen challenges in an ECC with administration of the drugs after 2 hours. Two challenges were conducted within the grass pollen season and two out of the grass pollen season. The active treatment significantly improved nasal symptoms and nasal flow and significantly reduced the amount of nasal secretion compared with placebo both within and outside of the pollen season (P < .0001 each). The treatment effect was not different between the seasons (P > .05). Controlled allergen provocation in an ECC can be used to test anti-allergic treatment both within and outside of the grass pollen season.