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Wise et al.

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NARES patients report symptoms that are typical, although often more pronounced, than those of PAR. These include, nasal congestion, profuse aqueous rhinorrhea, sneezing, and nasal and ocular pruritis. A prominent feature not shared with AR is anosmia, a frequent finding in NARES patients. 175 NARES is diagnosed by careful history, findings on physical exam (pale, boggy turbinates, like those found in PAR patients), and negative skin or in vitro allergy testing. Cytologic examination in NARES reveals the presence of prominent eosinophilia, usually 10% to 20% 173 on nasal smear, with a diagnostic criterion (described by some) of more than 25% eosinophilia. 176 In addition, nasal biopsies from these patients commonly show increased numbers of mast cells and prominent mast cell degranulation. 177,178 Research has supported the role of chronic inflammation in the development of NARES. Though there is still a lack of understanding as to the exact pathophysiology, studies have shown an increased transendothelial migration of eosinophils, attracted and activated by chemokines and cytokines. 179,180 Specifically, NARES is characterized by elevated nasal fluid levels of tryptase (also seen in PAR patients) and eosinophilic cationic protein (ECP) (markedly increased solely in NARES). 181 In addition, increased Th2 cytokines (interleukin [IL]-6 and IL-17) appear to be a factor in the remodeling process seen in NARES. 182 Other proinflammatory chemokines that have been implicated for their role in eosinophil chemotaxis and infiltration include macrophage/monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T-cell expressed and secreted (RANTES). Elevated RANTES concentrations have been found in the nasal fluid of patients with PAR and NARES. 183 Recently, Peric et al. 184 demonstrated a correlation between the concentration of RANTES with nasal symptoms and eosinophil counts in PAR patients. However, levels of MCP-1 and RANTES were significantly higher in the nasal fluid of NARES compared to PAR subjects, which again, correlated with nasal symptom scores and density of eosinophilia in these patients. Nasal neural dysfunction has also been described as a contributing factor to the symptomatology in NARES. 185 NARES usually occurs in isolation but may be associated with aspirin-exacerbated respiratory disease (AERD), characterized by asthma, nasal polyps, and NSAID intolerance. 173 NARES has also been identified as a risk factor for the induction or augmentation of obstructive sleep apnea (OSA). 186 The treatment of NAR centers on its underlying cause. Given the inflammatory changes demonstrated on nasal cytology and physical exam, NARES is primarily treated with INCS sprays. 154 This method of treatment is known to decrease neutrophil and eosinophil chemotaxis, reduce mast cell and basophil mediator release, and result in decreased mucosal edema and local inflammation. 187 The intranasal antihistamine azelastine is U.S. Food and Drug Administration (FDA)-approved for both AR and NAR. In clinical trials, azelastine has been shown to reduce symptoms of rhinitis, including postnasal drainage, sneezing, rhinorrhea, and congestion. 188 However, these multicentered, placebo-controlled trials studied azelastine for the treatment of vasomotor rhinitis (non-allergic rhinopathy) rather than NARES specifically.

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.