Ibon Eguiluz-Gracia, Ruben Fernandez-Santamaria and Almudena Testera-Montes contributed equally to this work. Clinical Implications: Nasal reactivity to aeroallergens with and without systemic IgE sensitization can coexist in the same rhinitis patient.

Background:The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR) and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility are scarce.Objective: To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls. Methods:A retrospective evaluation of the NACs conducted in our Unit for 2005-2017 and monitored by acoustic rhinometry and nasal-ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session [NAC-S & NAC-M]). The adverse events (AEs), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC-S performed at 1-2-month interval in AR, LAR and nonallergic rhinitis patients, and in healthy controls. Results: A total of 11 499 NACs were performed in 518 children and 5830 adults.Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC-S performed in 710 subjects were 97.32%, 100%, and 92.91%, respectively. There were no false-positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes. Conclusion:The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma. K E Y W O R D Slocal allergic rhinitis, nasal allergen challenge, reproducibility, safety Abbreviations: AE, adverse event; AIT, allergen immunotherapy; AR, allergic rhinitis; DP, Dermatophagoides pteronyssinus; EAACI, European Academy of Allergy and Clinical Immunology; FEV1, forced respiratory volume in the first second; HC, healthy control individual; IQR, interquartile range; LAR, local allergic rhinitis; NAC-M, NAC with multiple allergens per session; NAC, nasal allergen challenge; NAC-S, NAC with a single allergen per session; NAR, nonallergic rhinitis; NHR, nasal hyperreactivity; NPV, negative predictive value; PPV, positive predictive value; sIgE, allergen-specific IgE; SPT, skin prick test; Vol 2-6 cm, volume 2-6 cm of each nostril.Eguiluz-Gracia and Testera-Montes contributed equally to this paper.

Background 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. Methods 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. Results 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. Conclusions LAR and DAR represent relevant differential diagnosis in pediatric rhinitis. NAC increases the diagnostic accuracy of clinical algorithms for rhinitis in children and adolescents.

A l g o r i t h m s i n A l l e r g y a n d C l i n i c a l I m m u n o l o g y

Testera-Montes, Palomares, Jurado-Escobar, Rondon and Eguiluz-Gracia contributed equally to this work.

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Local respiratory allergy (LRA) is defined by the negativity of atopy tests, a clinical history suggestive of airway allergy and a positive response to the nasal and/or bronchial allergen challenge. The clinical spectrum of LRA is comprised of three conditions: local allergic rhinitis (LAR) and local allergic asthma in non-atopic patients, and dual allergic rhinitis (coexistence of allergic rhinitis and LAR) in atopic individuals. LRA is an independent disease phenotype not progressing to atopy over time, but naturally evolving to the clinical worsening and the onset of comorbidities. Published data suggests that LRA is mediated through the mucosal synthesis of allergen-specific (s)IgE, which binds to FcϵRI on resident mast cells, and in >50% of cases traffics to the blood stream to sensitize circulating basophils. To date, 4 clinical trials have demonstrated the capacity of allergen immunotherapy (AIT) to decrease nasal, conjunctival and bronchial symptoms, to improve quality of life, to increase the threshold dose of allergen eliciting respiratory symptoms, and to induce serum sIgG4 in LRA individuals. Collectively, these data indicate that local allergy is a relevant disease mechanisms in both atopic and non-atopic patients with airway diseases.

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