UNASSIGNED: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia.
UNASSIGNED: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye\'s largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy.
UNASSIGNED: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season.
UNASSIGNED: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean.

BACKGROUND: Nasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose-responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR.
METHODS: Sixteen volunteers with HDM-induced perennial AR and 15 volunteers with SB pollen-induced seasonal rhinitis underwent a graded up-dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0-12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10 min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 (\"provoking dose 7\") in most allergic participants was identified. NACs using the \"provoking dose 7\" were performed on 5 non-allergic individuals to test for irritant effects. The \"provoking dose 7\" of HDM extract was used in a subgroup of two SB allergic, non-HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses.
RESULTS: Most patients experienced a TNSS of at least 7/12 at a median concentration of 1500 AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500 AU/mL concentrations were performed on 5 non-allergic individuals with no symptomatic or PNIF response. 1500 AU/mL of HDM extract produced no symptoms in SB allergics nor 1500 AU/mL SB extract in HDM allergics.
CONCLUSIONS: For both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate-severity response (\"provoking dose 7/12\") was 1500 AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR.

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.
OBJECTIVE: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT.
METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed.
RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ.
CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

UNASSIGNED: Pollen 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.
UNASSIGNED: This 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.
UNASSIGNED: The 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.
UNASSIGNED: EEC 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.

The prevalence of cat allergen-induced AR is increasing worldwide, prompting its study using controlled methodology. Three general categories of allergen exposure models currently exist for the study of cat allergen-induced AR: natural exposure cat rooms, allergen exposure chambers (AEC), and nasal allergen challenges (NAC). We evaluated existing literature surrounding the use of these models to study cat allergen induced AR using online research databases, including OVID Medline, Embase, and Web of Science. We report that natural exposure cat rooms have been important in establishing the foundation for our understanding of cat allergen-induced AR. Major limitations, including variable allergen ranges and differing study designs highlight the need for a more standardized protocol. In comparison, AECs are an exceptional model to mimic real-world allergen exposure and study long-term implications of AR with large sample sizes. Existing AECs are limited by heterogeneous facility designs, differing methods of cat allergen distribution, and issues surrounding cost and accessibility. Conversely, NACs allow for smaller participant cohorts for easier biological sampling and are ideal for phase I, phase 2 or proof-of-concept studies. NACs generally have a standardized protocol and are less expensive compared to AECs. Nevertheless, NACs solely capture acute allergen exposure and have the further limitation of using allergen extracts rather than natural allergen. As the use of combined controlled methodologies is sparse, we recommend concurrent use of AECs and NACs to study short- and long-term effects of AR, thereby providing a more holistic representation of cat allergen-induced AR.

BACKGROUND: Allergy skin test reliability depends on the reagents and controls selected. Histamine is used at 1 mg/ml and 6 mg/ml concentration but few studies address the rationale for selecting one versus the other and how this may impact diagnostic accuracy.
OBJECTIVE: To determine the rate of false negative allergen skin tests responses between UniTest PC (using the 1 mg/mL histamine) and Quintip devices (using 6 mg/mL) for 4 common aeroallergens.
METHODS: Subjects aged 18-65 with symptoms of allergy to cat and/or ragweed received skin testing with 4 aeroallergens (dust mite mix, timothy grass, ragweed, cat), histamine and control diluent. Those individuals who tested positive to cat or ragweed with one skin prick test (SPT) device but not the other then proceeded to nasal allergen challenge (NAC). The primary outcomes were the aeroallergen false negative rates and sensitivities of the skin test devices followed by nasal allergen (NAC).
RESULTS: Twenty-five individuals were recruited and underwent a total of 300 SPTs. SPT to allergens (ragweed, dust mite, cat, and timothy grass) resulted in a statistically significant difference in wheal size among the two skin testing devices (p value <0.0001, 0.0001, 0.0006, and 0.0053 respectively). Six NAC procedures were performed to cat/ragweed and 5 of 6 (83% were positive). The overall allergen sensitivity rate for UniTest and Quintip were 97% and 78% respectively with most false negatives due to the use of 6 mg/ml histamine control reagent.
CONCLUSIONS: Our study shows that 6 mg/ml concentration of histamine control reagent may contribute to a false interpretation of aeroallergen skin prick test results.

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UNASSIGNED: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment option for allergic rhinitis (AR) patients with persistent moderate-severe AR for whom traditional pharmacotherapies are ineffective. The nasal allergen challenge (NAC) and allergen exposure chamber (AEC) are two translational models of AR that can be used to investigate the properties, safety, and efficacy of AIT.
UNASSIGNED: Peer-reviewed, human-centered articles utilizing AEC or NAC models to investigate AIT between 2010 and 2020 were curated from PubMed, EMBASE, and OVID Medline databases. AECs have been used to evaluate traditional subcutaneous and sublingual administrations of AIT, including cross-protective effects and different dosing regimens. More recently, the effectiveness of novel AIT formulations has been evaluated. NACs are another model used to study AIT, including using novel intralymphatic routes of administration. It is an especially powerful and versatile tool to determine if basic science and animal model findings are clinically translatable.
UNASSIGNED: The AEC and NAC models both produce clinically relevant and reproducible results. AECs are more effective for studying many participants but are limited because they require a specialized facility. As more AIT therapies and new formulations are developed over time, the versatility of the NAC will be especially useful.

Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study\'s objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma.
Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381-11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T-cell activation and IL-5 production were measured in peripheral blood mononuclear cells.
67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380-0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (P = .03), lower cockroach-specific IgG/IgE ratios (children, P = .002), and increased cockroach-specific IL-5-producing T lymphocytes (P = .045). The NAC was well tolerated.
We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.

Three allergic phenotypes of rhinitis have been described in adults: allergic rhinitis (AR), local allergic rhinitis (LAR), and dual allergic rhinitis (DAR, coexistence of AR and LAR). Nevertheless, most centers follow a diagnostic approach only based on skin prick test and serum allergen-specific IgE (collectively called atopy tests, AT). This approach prevents the recognition of LAR and DAR, the diagnosis of which requires a nasal allergen challenge (NAC). Here, we investigate the existence of LAR and DAR phenotypes in children and adolescents, and the misdiagnosis rate associated with a work-up exclusively based on AT.
Clinical data were obtained during physician-conducted interviews, and AT and NAC were systematically performed in 5- to 18-year-old patients with chronic rhinitis. The misdiagnosis rate was defined as the proportion of cases where AT and NAC results were discordant.
A total of 173 patients (mean age 15.1 years, 39.9% male) completed the study. AR (positive AT and NAC), LAR (negative AT and positive NAC), DAR (positive AT and NAC for some allergens and negative AT and positive NAC for other allergens), and non-allergic rhinitis (negative NAC) were diagnosed in 45.7%, 24.9%, 11.6%, and 17.9% of individuals, respectively. The clinical profile was comparable among allergic phenotypes, but allergic patients had a significantly earlier rhinitis onset, higher conjunctivitis prevalence, and more severe disease than NAR individuals. A diagnostic work-up exclusively based on AT misclassified 37.6% of patients.
LAR and DAR represent relevant differential diagnosis in pediatric rhinitis. NAC increases the diagnostic accuracy of clinical algorithms for rhinitis in children and adolescents.