Safety and reproducibility of nasal allergen challenge

Abstract

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.

How to Diagnose and Treat Local Allergic Rhinitis: A Challenge for Clinicians

“…The NAC can be also considered positive if moderate changes occur simultaneously in both parameters [8]. In the above-mentioned study, we also report a very high reproducibility for the NAC (97.32%, PPV 100%, NPV 92.92%) when assessed by Lebel symptoms score and acoustic rhinometry [68]. This analysis was based on three consecutive NACs performed with the same allergen in 710 patients with 1–2-month interval, to avoid the evolution bias.…”

“…The NAC is the gold standard for LAR diagnosis, as it displays the optimal sensitivity and specificity [10,13,14]. A recent study from our group including data from 11499 procedures performed in 518 children and 5830 adults (1547 of them with asthma symptoms), demonstrated that the NAC is an extremely safe technique (99.97% of the procedures were well tolerated) [68]. Of note, the allergen administration by nasal spray or micropipette were equally safe [68].…”

“…A recent study from our group including data from 11499 procedures performed in 518 children and 5830 adults (1547 of them with asthma symptoms), demonstrated that the NAC is an extremely safe technique (99.97% of the procedures were well tolerated) [68]. Of note, the allergen administration by nasal spray or micropipette were equally safe [68]. A recent position paper of the European Academy of Allergy and Clinical Immunology has progressed in the harmonization of the NAC procedure [8].…”

Allergen Immunotherapy in Children User’s Guide

“…According to an EAACI position paper in 2017, potential biomarkers for monitorization of the clinical efficacy of AIT were summarized as follows: a) IgE (total IgE, sIgE/total IgE) b) subclasses of IgG (allergen‐specific IgG, IgG1 and sIgG4, sIgE/IgG4 ratio) c) IgE serum inhibitory activity for IgE (IgE‐FAB), d) basophil activation, e) chemokines and cytokines, f) cell markers such as Tregs, Bregs, and DCs, and g) in vivo biomarkers including provocation tests …”

Local allergic rhinitis: a pediatric perspective

“…Both NAC-S and NAC-M protocols have proven to be safe. 49 Determining sIgE in nasal secretions is a noninvasive method and is highly specific; however, it has been found to have low sensitivity in most studies (22-40% of responses), a fact that can be attributed to the dilution effect, or other factors. 12,13 A recent study performed by Meng et al 50 found a quite high diagnostic accuracy for nasal sIgE in LAR diagnosis.…”