Non allergic rhinitis (NAR)
Non allergic rhinitis in children is poorly defined [26]. Previously AR was clearly discriminated by NAR by means of increased local total/local IgE specific levels and nasal eosinophils and these differences were more pronounced in children than adults with AR, suggesting that AR in children is a more distinct feature [27]. However, inflammatory mediators related to different inflammatory endotypes detected from nasal cytology cannot discriminate AR from NAR adult patients [28].
Local allergic rhinitis (LAR) in children is an emerging disease, highly underdiagnosed [29]. Increased levels of local IgE in the nasal lavage fluid has been proposed as a useful biomarker in children with suspected LAR [30]. Local production of “T2” inflammatory mediators has been demonstrated following nasal allergen challenges in a pediatric setting [31]. Nevertheless, AR and LAR share several clinical and immune features, such as positive response to a nasal allergen provocation test, increased risk of asthma occurrence and increased nasal IgE production [32]. Moreover, the FcepsilonR1beta genetic polymorphism has been linked both with LAR and AR prevalence [33].
Nasal hyperreactivity (NHR) constitutes a cardinal clinical feature both in AR and NAR [34] and has been previously documented in children with allergic rhinitis, although respective techniques are difficult to apply in clinical use and young ages [35, 36]. The most well described pathogenetic mechanism involves a “dysregulated” neural innervation network. In NAR and NHR, the role of the efferent component via the activated transient receptor potential (TRP) ion channels (receptor 1_TRPA1 and subfamily V-TRPV1), induces the release of neuropeptides, such as CGRP and substance P (SP), neurokinin A and B from sensory nerve endings, which in turn induce sneezing, mucus production and congestion [37]. In line, histological data are indicative of increased expression of the aforementioned neuropeptides of the nasal mucosa in patients with NHR and NAR [38]. Moreover, the impact of environmental and microbial factors (i.e.; staphylococcus Aureus enterotoxins) has been postulated for triggering local nerve endings, more so in the presence of a disrupted epithelium barrier [39]. It remains to be elucidated whether barrier dysfunction is a primary (genetic) defect or secondary to infectious agents or allergens [40, 41].