Prevalence of Local IgE Elevation and Its Effect on Intranasal Capsaicin Therapy in the Nonallergic Rhinitis Population

Intranasal capsaicin has been described as a novel therapeutic option for nonallergic rhinitis through downregulation and degeneration of the TRPV-1 receptor, which leads to decreased nasal activation by agonists [1, 2]. Prior studies have focused on 0.1 mmol/L administration, although concentrations up to 0.5 mmol/L were found to be tolerable for patients in prior studies [3]. Our study aims are to: (i) evaluate the therapeutic effect of capsaicin on chronic rhinitis symptoms in a larger cohort with higher concentrations of capsaicin administration; and (ii) delineate the relationship between local IgE levels and chronic rhinitis symptomatology and association with response to capsaicin treatment. Capsaicin was used for the treatment of nonallergic rhinitis with a reduction in symptoms at 12 weeks. Patients tolerated clinic treatment with capsaicin and were compliant with home treatment. Regardless of baseline IgE level in the nasal mucosa, patients receive benefit from capsaicin. The study protocol was approved by the University of Texas Health Sciences Center at Houston Institutional Review Board, and complete study results are reported in clinicaltrials.gov (NCT05093478). Inclusion criteria for the study included patients with nonallergic rhinitis. Patients with a diagnosis of allergic rhinitis or positive allergy testing were excluded. Patients first completed a screening visit, where they completed skin prick allergy testing using Multi-Test II (Lincoln Diagnostics, Decatur, IL) to six common allergens. Patients who yielded positive results were excluded from study enrollment. In order to create a standardized capsaicin solution, capsaicin powder (Fisher Scientific, Waltham, MA) was compounded to formulate a 0.1 and 0.5 mmol/L solution. Seven patients were given 0.1 mmol/L capsaicin solution, and 21 patients were given 0.5 mmol/L capsaicin solution. One milliliter of capsaicin formulation was applied to each nasal cavity using a mucosal atomizer device in the clinic. After initial administration, patients were given their corresponding capsaicin solution and instructed to apply it intranasally for four additional treatments at home. The visual analog score (VAS) was employed to quantitatively rate symptom severity [4]. Patients rated severity from 0 to 10, which was summated to create a total symptom score (TSS). Mucosal brush biopsy was utilized for intranasal IgE harvesting in accordance with a standardized technique (Immunovent LLC; New York, NY) [5]. Data collection was performed during three separate intervals: initial recruitment with capsaicin administration, 4-week follow-up, and 12-week follow-up. The statistical significance of mean changes between symptom scores prior to treatment and post-treatment at 4 and 12 weeks was evaluated using the Wilcoxon signed rank test (p < 0.05). The initial recruitment phase included a total of 28 patients. Twenty-eight patients reported VAS symptom scores at the 4-week visit, and 24 patients reported their final 12-week VAS symptom scores, with four lost to follow-up. Of these 24 patients who were still enrolled in the study, 19 patients returned to the clinic for the final IgE measurement. The mean age of patients was 63 years (SD ±16 years), and the ratio of females to males was 1:1. The average baseline TSS score for the initial 28 patients was 17.0 (SD ±7.0), with rhinorrhea as the most severe symptom in the majority of patients. At the 4-week follow-up, all patients reported a reduction of symptoms, with 21 patients reporting a TSS score decrease greater than 30% from baseline (Table 1). At the 12-week follow-up, 21 (87.5%) of remaining patients reported improvement in symptoms, with 14 patients (14/21, 66.7%) reporting a TSS score decrease greater than 30% from baseline. The patients who received the 0.1 and 0.5 mmol/L solutions had a mean reduction in TSS score at 12 weeks of 5 and 7.4, respectively. There was no significant correlation between baseline local IgE level and pretreatment VAS. There was no relationship between baseline IgE level and reduction in TSS with treatment at 12 weeks (r = −0.15, p = 0.47) (Table 2). There were no significant adverse events noted during the study period. In general, patients noted a burning sensation with capsaicin, although every patient was able to complete the five-dose administration at the treatment visit. A prior Cochrane review, as well as a recent meta-analysis that included nine studies, concluded that capsaicin is a reasonable treatment option under physician supervision for patients with idiopathic, nonallergic rhinitis [6, 7]. The four studies included within the meta-analysis that noted concentration utilized a dosage of 0.1 mmol/L solution. Our results suggested a larger improvement in symptom score from baseline with the 0.5 mmol/L concentration (Supporting Information). Both the 0.1 and 0.5 mmol/L concentrations noted less reduction in TSS from baseline to 12-week post-treatment when compared to the 4-week post-treatment. The mechanism of action of capsaicin has previously been elucidated and thought to cause desensitization and degeneration of the TRPV1 receptor, leading to decreased activation by agonists that induce nasal hyperreactivity [8]. Given these results, a higher concentration of capsaicin may be desensitizing a higher number of receptors, leading to improved treatment effect, but these receptors may be recovering or upregulating over time, which could explain attenuation of clinical therapeutic efficacy. Every patient in our cohort had clinically detectable levels of local IgE in their mucosal brush biopsy. There was no correlation between baseline and 12 week local IgE levels with change in TSS on the VAS from baseline to 12 weeks. This is similar to a prior study in which mucosal brush biopsy yielded 100% prevalence of detectable intranasal IgE levels in nonallergic rhinitis patients, and there was discordance between total intranasal IgE levels, quality of life scores, and seasonal symptoms [5]. These findings do not allow us to establish a correlative association between capsaicin treatment and total IgE levels in the nasal mucosa. The underlying supposition is that the neurogenic mechanism of action of capsaicin may be completely independent of a localized allergic type 2 immune pathway. Prior studies have noted that capsaicin does not interfere with nasal epithelial morphology or induce apoptosis or necrosis in mast cells or nasal epithelial cells, so it may not affect the nasal microenvironment [8]. One limitation in this study was subject attrition, notably for the in-person follow-up for mucosal IgE collection. Many patients who were recruited wished to avoid procedural interventions and/or found daily sprays to be too disruptive. Therefore, there is inherent sampling bias. Ten patients who followed up in person at the 12-week visit requested and were given a repeat capsaicin treatment, reinforcing that anticipated therapeutic benefits outweighed perceived tribulation with treatment. The authors received funding from the American Academy of Otolaryngic Allergy Foundation Grant. MC: consultant for 3D Matrix, Acclarent, Latica, MicroGenDx, and Medtronic. AL: consultant for Lyra Therapeutics, Maxwell Bioscience, Stryker ENT, Medtronic, NeurENT, SoundHealth, and Sanofi; advisory board member for AstraZeneca, GlaxoSmithKline, and Sanofi; grant support from Insmed and Sanofi. WY: consultant for Aerin Medical and Optinose Inc. 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