Christine Segboer

Nasal hyper-reactivity is a common feature in both allergic and nonallergic rhinitis

Nasal hyper‐reactivity is an increased sensitivity of the nasal mucosa to various nonspecific stimuli. Both allergic rhinitis (AR) and nonallergic rhinitis (NAR) patients can elicit nasal hyper‐reactivity symptoms. Differences in the prevalence or type of nasal hyper‐reactivity in AR and NAR patients are largely unknown. In this study, we quantitatively and qualitatively assessed nasal hyper‐reactivity in AR and NAR.

Role of Innate Immunity in the Pathogenesis of Chronic Rhinosinusitis: Progress and New Avenues

Chronic rhinosinusitis is a heterogeneous and multifactorial disease with unknown etiology. Aberrant responses to microorganisms have been suggested to play a role in the pathophysiology of the disease. Research has focused on the presence, detection, response to, and eradication of these potential threats. Main topics seem to center on the contribution of structural cells such as epithelium and fibroblasts, on the consequences of activation of pattern-recognition receptors, and on the role of antimicrobial agents. This research should be viewed not only in the light of a comparison between healthy and diseased individuals, but also in a comparison between patients who do or do not respond to treatment. New players that could play a role in the pathophysiology seem to surface at regular intervals, adding to our understanding (and the complexity) of the disease and opening new avenues that may help fight this incapacitating disease.

Inhibition of capsaicin‐driven nasal hyper‐reactivity by SB‐705498, a TRPV1 antagonist

AIMS To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal SB-705498, a selective TRPV1 antagonist. METHODS Two randomized, double-blind, placebo-controlled, clinical studies were performed: (i) an intranasal SB-705498 first time in human study to examine the safety and PK of five single escalating doses from 0.5 to 12 mg and of repeat dosing with 6 mg and 12 mg twice daily for 14 days and (ii) a PD efficacy study in subjects with non-allergic rhinitis (NAR) to evaluate the effect of 12 mg intranasal SB-705498 against nasal capsaicin challenge. RESULTS Single and repeat dosing with intranasal SB-705498 was safe and well tolerated. The overall frequency of adverse events was similar for SB-705498 and placebo and no dose-dependent increase was observed. Administration of SB-705498 resulted in less than dose proportional AUC(0,12 h) and Cmax , while repeat dosing from day 1 to day 14 led to its accumulation. SB-705498 receptor occupancy in nasal tissue was estimated to be high (>80%). Administration of 12 mg SB-705498 to patients with NAR induced a marked reduction in total symptom scores triggered by nasal capsaicin challenge. Inhibition of rhinorrhoea, nasal congestion and burning sensation was associated with 2- to 4-fold shift in capsaicin potency. CONCLUSIONS Intranasal SB-705498 has an appropriate safety and PK profile for development in humans and achieves clinically relevant attenuation of capsaicin-provoked rhinitis symptoms in patients with NAR. The potential impact intranasal SB-705498 may have in rhinitis treatment deserves further evaluation.

Capsaicin for Rhinitis

Rhinitis is a multifactorial disease characterized by symptoms of sneezing, rhinorrhea, postnasal drip, and nasal congestion. Non-allergic rhinitis is characterized by rhinitis symptoms without systemic sensitization of infectious etiology. Based on endotypes, we can categorize non-allergic rhinitis into an inflammatory endotype with usually eosinophilic inflammation encompassing at least NARES and LAR and part of the drug induced rhinitis (e.g., aspirin intolerance) and a neurogenic endotype encompassing idiopathic rhinitis, gustatory rhinitis, and rhinitis of the elderly. Patients with idiopathic rhinitis have a higher baseline TRPV1 expression in the nasal mucosa than healthy controls. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of chili peppers, plants of the genus Capsicum. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. Patients with idiopathic rhinitis benefit from intranasal treatment with capsaicin. Expression of TRPV1 is reduced in patients with idiopathic rhinitis after capsaicin treatment. Recently, in a Cochrane review, the effectiveness of capsaicin in the management of idiopathic rhinitis was evaluated and the authors concluded that given that many other options do not work well in non-allergic rhinitis, capsaicin is a reasonable option to try under physician supervision. Capsaicin has not been shown to be effective in allergic rhinitis nor in other forms of non-allergic rhinitis like the inflammatory endotypes or other neurogenic endotypes like rhinitis of the elderly or smoking induced rhinitis.

Quality of life is significantly impaired in non-allergic rhinitis patients

In contrast to the well‐known significant impairment of quality of life (QoL) in allergic rhinitis (AR), the degree of impairment in QoL in nonallergic rhinitis (NAR) remained unknown for a long time, due to a lack of a validated questionnaire to assess QoL in the NAR patient group. In this study, a validation of the mini‐RQLQ questionnaire in NAR patients was performed, followed by an assessment of QoL in NAR patients compared to AR and healthy controls. Secondly, use of medication and treatment satisfaction in AR and NAR was assessed.

Endotyping of non-allergic, allergic and mixed rhinitis patients using a broad panel of biomarkers in nasal secretions.

Background Endotyping chronic rhinitis has proven hardest for the subgroup of non-allergic rhinitis (NAR) patients. While IgE-related inflammation is typical for allergic rhinitis (AR), no markers have been found that can be seen to positively identify NAR. A further complication is that AR and NAR might co-exist in patients with mixed rhinitis. As previous studies have considered only a limited number of inflammatory mediators, we wanted to explore whether a wider panel of mediators could help us refine the endotyping in chronic rhinitis patients. Objective To endotype chronic rhinitis, and non-allergic rhinitis in particular, with help of molecular or cellular markers. Method In this study we included 23 NAR patients without allergen sensitizations and with persistent rhinitis symptoms, 22 pollen sensitized rhinitis patients with seasonal symptoms, 21 mixed rhinitis patients with pollen-related symptoms and persistent symptoms outside of the pollen season, and 23 healthy controls without any symptoms. Nasal secretions were collected outside of pollen season and differences between the endotypes were assessed for a broad range of inflammatory mediators and growths factors using a multiplex ELISA. Results Although we were able to identify two new nasal secretion makers (IL-12 and HGF) that were low in mixed and AR patients versus NAR and healthy controls, the most intriguing outcome is that despite investigating 29 general inflammatory mediators and growth factors no clear profile of non-allergic or mixed rhinitis could be found. Conclusion Classical inflammatory markers are not able to differentiate between non-allergic or mixed rhinitis patients and healthy controls.

New insights into the pathogenesis of non-allergic rhinitis

Background Effective treatment requires a correct diagnosis, however for different subgroups of chronic rhinitis patients differentiation on a clinical level is complicated. In the case of non-allergic rhinitis (NAR) that represents a wide spectrum of diseases, we are also faced with a missing mechanistic or molecular diagnosis. Here we present an unbiased transcriptomic approach on nasal epithelial cells that assess expression differences between chronic rhinitis subgroups.

New Findings in Nonallergic Rhinitis and Local Allergic Rhinitis

Research in rhinitis has primarily focused on allergic rhinitis and important aspects of the disease such as the IgE-mediated inflammatory cascade, the impact on quality of life, the impact on the lower airways, and control and severity of the disease, especially in those patients in which control is not easily obtained. However, a significant number of patients with persistent rhinitis do not show systemic sensitization to aeroallergens or signs of infection. These patients are defined under the umbrella term “nonallergic rhinitis” or “noninfectious rhinitis.” Nonallergic rhinitis comprises a large number of phenotypes and endotypes, such as rhinitis medicamentosa, drug-induced rhinitis, rhinitis of the elderly, idiopathic rhinitis, and local allergic rhinitis. This review describes the new pathophysiology and clinical insights into these different forms of nonallergic rhinitis with special emphasis on local allergy. New recommendations in diagnosis and treatment are given.

Quality of life and use of medication in chronic allergic and non-allergic rhinitis patients

In contrast to the significant number of studies indicating the impairment of QoL in AR, the degree of impairment in Quality of Life (QoL) in NAR remains underexposed. Again in contrast to AR, almost no evidence-based therapies for NAR patients exist. We assessed QoL in NAR compared to healthy controls and AR patients as positive controls and investigated whether the use of treatment in patients with NAR and AR had effect on QoL.