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.

Local allergic rhinitis (LAR) is defined by a clinical history suggestive of allergic rhinitis (AR), negativity of systemic IgE measurement and positive response to nasal allergen challenge (NAC). The term local respiratory allergy includes LAR, local allergic asthma (positive response in bronchial allergen challenge) and dual allergic rhinitis defined by the coexistence of AR and LAR. LAR worsens in severity and presence of comorbidities over time, and it is an independent entity from AR. Prevalence is higher in Mediterranean countries. LAR onset occurs during childhood in 36% of cases. Physiopathological features of LAR are: increased nasal eosinophilic inflammation, tryptase and eosinophil cationic protein, and presence of nasal specific IgE in secretions of 20-40% of subjects. A recent study demonstrated increase in sequential class switch recombination to IgE markers in mucosa of LAR with accumulation of IgE+ CD38+ plasmablasts. Moreover, there is increased expression in B cells of mucosal homing receptors CXCR3+ and CXCR4 in peripheral blood, with accumulation of Th9 and Th2 cells. NAC is the gold standard in the diagnosis of LAR. The measurement of specific IgE in nasal secretions basophil activation test or are still not suitable for diagnosis. There is ample evidence of the usefulness of allergen immunotherapy in the treatment in LAR after 4 DBPCRT in 152 patients. In conclusion, knowledge about LAR is continuously increasing, with detailed definition of physiopathological mechanisms and new phenotypes. More awareness of the disease should be promoted among different specialists, and NAC must be considered an essential diagnostic tool in any age group, including children.

Background. Local Allergic Rhinitis (LAR) is a phenotype defined by rhinitis symptoms with negative responses to systemic sensitization tests but with an exclusively nasal allergic inflammatory response. Data on the pediatric age group is scarce, and no Latin American data has been published so far. Methods. Nasal Allergen Challenge (NAC) was performed with Dermatophagoides pteronyssinus and Blomia tropicalis in six- to 18-year-old patients diagnosed with rhinitis and no systemic sensitization. NAC was monitored using subjective parameters and acoustic rhinometry. The study aimed to identify LAR in child and adolescent subjects previously diagnosed with non-allergic rhinitis (NAR) in a Brazilian specialty outpatient clinic (Allergy and Immunology). Results. During the study period, we analyzed 758 skin prick tests (SPT). Of those, 517 (68.2%) were diagnosed with rhinitis. Among those, 18.4% (95/517) had a negative SPT, meeting the criteria for inclusion in the study. Twenty-five patients underwent NAC, and 40% (10/25) of them, previously considered to have NAR, had a positive test and were reclassified as having LAR. Based on the analyzed characteristics, clinically differentiating LAR from NAR was impossible. Conclusions. This study represents the first investigation of LAR in child and adolescent subjects in Latin America, contributing significantly to the understanding of its prevalence and characteristics in this geographic area. Among a subgroup of patients lacking systemic sensitization submitted to NAC, 40% (10/25) demonstrated a positive NAC with Dermatophagoides pteronyssinus and Blomia tropicalis, warranting their reclassification to LAR. NAC with multiple allergens has been proven safe and viable in pediatric populations, affirming its critical role in the accurate diagnosis of LAR.

Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators.
20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 μg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS.
NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS.
NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.

There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the \"late allergic response,\" which occurs in approximately 40% to 50% of patients with allergy.
We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response.
In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements.
Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours.
IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.

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.

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.

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.