Idiopathic Rhinitis Research Articles

Nasal discharge in dogs - are microbiological and histopathological examinations clinically useful?

Retrospective evaluation of the diagnostic value of bacterial culture of nasal mucosal swabs and histopathologic assessment of nasal mucosal biopsies in dogs with nasal discharge. Medical records of dogs with the predominant clinical sign of nasal discharge that were referred to the ENT Unit of the Small Animal Department between January 2015 and December 2016 were reviewed. Data of 85 dogs were evaluated. On the basis of the results of computed tomography (CT), rhinoscopy, bacterial culture of a nasal mucosal swab and histopathologic examination of nasal mucosal biopsies, dogs were assigned to one of six groups of primary nasal diseases: nasal neoplasia (24/85, 28 %), oronasal defect (22/85, 26 %), idiopathic chronic rhinitis (17/85, 20 %), foreign body (8/85, 10 %), sinonasal aspergillosis (7/85, 8 %) and diseases of the planum nasale (7/85, 8 %). In brachycephalic dogs (14/85, 17 %), oronasal defects (8/14, 57 %) were the most frequent cause of nasal discharge. No cases of a primary bacterial infection of the nasal cavity were observed and, therefore, antibiotic treatment had not been successful. Nevertheless, 72 % of the dogs in this study had received prior antibiotic treatment. Secondary bacterial infec tions diagnosed via nasal mucosal swabs were not diagnostic for the underlying primary nasal diseases. Targeted biopsies of tumors obtained under endoscopic visualization may lead to a definitive diagnosis, whereas biopsies of the nasal mucosa and the type of the inflammatory infiltrate were not diagnostic. Nasal discharge in dogs is frequently an indicator of an underlying severe primary nasal disease possibly leading to mortality of the affected dogs. Further diagnostics under anesthesia should be performed early in the diagnostic evaluation. Rhinoscopy as the central diagnostic is supported by CT and biopsy. Bacterial culture of the nasal discharge does not provide a diagnosis for the primary nasal disease process. Without further diagnostics, antibiotic treatment of dogs presenting with nasal discharge is considered as not appropriate and can be harmful in dogs with nasal tumors or sinonasal aspergillosis. When an intranasal malignant neoplasia is suspected, endoscopic-guided biopsies of the nasal mass should be obtained, because blind nasal biopsies are associated with a high rate of false-negative results.

Enhanced chemosensory sensitivity in idiopathic rhinitis patients and its reversal by nasal capsaicin treatment.

We recently showed that the therapeutic action of capsaicin treatment in idiopathic rhinitis (IR) is based on the ablation of the TRPV1-Substance P nociceptive signaling pathway (Van Gerven et al., JACI 2013). However, the functional consequences of capsaicin treatment on nasal nerve activation remain unknown. A double-blinded placebo-controlled trial, involving 33 IR patients and 12 healthy controls (HC). Nasal mucosal potentials (NMP) were evoked by exposing the nasal mucosa of IR patients and HC to an aerosol with different TRP-agonists. Low concentrations of 3 irritants (cinnamaldehyde, allyl isothiocyanate (mustard oil, MO) and capsaicin) that activate TRPA1 and/or TRPV1 were applied. The threshold for each irritant was determined for each individual as the dose at which a clear change from baseline in NMP was recorded. The threshold for MO was 5 mM in 9 %, 10 mM in 18% and 20 mM in 73% of HC, whereas for IR patients, 31.5% responded by an NMP-decrease at 5 mM, 37% on 10 mM and 31.5% on 20 mM. The MO-threshold was overall significantly lower for IR patients compared to HC (P = 0.0423). Remarkably, no changes in NMP measurements could be documented after cinnamaldehyde. Capsaicin exposure induced cough that hampered NMP recording. The lower chemical threshold to react to MO in IR patients compared to HC confirmed the specific role of these nociceptors in the pathophysiology of IR, which in turn, may help to design more specific and effective therapies.

Endotypes of chronic rhinitis: A cluster analysis study.

Chronic rhinitis (CR) is currently regarded as a syndrome, which presents as several endotypes. The aim of this study was to identify the CR endotype clusters and investigate the inflammatory patterns associated with the different endotypes. A total of 259 CR patients and 20 control subjects were enrolled in this prospective study. Twelve clinical variables were analyzed using cluster analysis and five inflammatory variables were measured to investigate the inflammatory patterns associated with the different clusters. Six endotype clusters of CR were defined in the Chinese CR patients. Patients in cluster 1 (38.6%) were diagnosed as allergic rhinitis (AR) without asthma, and in cluster 2 (13.5%) as AR with asthma, with all demonstrating positive results for local eosinophils and high levels of local and serum IgE. Similarly, patients in cluster 3 (18.6%) were diagnosed as nonallergic rhinitis with eosinophilia syndrome (NARES) without asthma and in cluster 5 (5.0%) as NARES with asthma, with all demonstrating positive results for local eosinophils, and negative results for both local and serum IgE. Patients in cluster 4 (4.6%) were diagnosed as local allergic rhinitis and showed positive results for local eosinophils and local IgE, but negative results for serum IgE, whereas patients in cluster 6 (19.7%) were diagnosed as idiopathic rhinitis because of high symptoms scores, but negative findings for local eosinophils, local IgE, and serum IgE. Chinese CR patients may be clustered into six endotypes with different inflammatory patterns, which may help in delivering individualized treatment.

The evaluation of three treatment protocols using oral prednisone and oral meloxicam for therapy of canine idiopathic lymphoplasmacytic rhinitis: a pilot study

BackgroundIdiopathic lymphoplasmacytic rhinitis (LPR) is a common inflammatory disorder of the nasal cavity in dogs due to unknown etiology. It is characterised by non-specific clinical signs, including nasal discharge, epistaxis and breathing problems. Diagnosis is usually based on the histopathologic identification of infiltrating plasmocytes and lymphocytes in the nasal mucosa and the exclusion of other underlying diseases. Treatment strategies include glucocorticoids, non-steroidal anti-inflammatory drugs, antibiotics and antifungal medications. The aim of this study was to evaluate the efficacy of various therapeutic protocols for managing canine lymphoplasmacytic rhinitis based on the results of clinical, endoscopic and histological examinations, and to determine the relapse rate for LPR in dogs.Twenty dogs of different breeds and both sexes, aged 1 to 14 years, were divided into four groups, each consisting of five dogs, including three experimental groups diagnosed with LPR and a control group.The dogs from the first experimental group were administered prednisone orally at 1 mg/kg/day in the first 4 weeks and 0,5 mg/kg/day in the following 2 weeks. The second group of dogs was administered meloxicam orally at 0,1 mg/kg/day in the first 3 weeks, followed by prednisone at 1 mg/kg/day in the following 2 weeks and 0,5 mg/kg/day in the last week of the treatment. The dogs from the third experimental group were administered meloxicam orally at 0,1 mg/kg/day for 6 weeks. The control group of dogs was administered empty gelatin capsules (placebo) orally for 6 weeks. Clinical signs, endoscopic and histopathologic lesions were scored before and after treatment. Groups were compared using Chi- squared statistics in a 2 × 2 table for pre- versus post-treatment scores.ResultsClinical signs persisted in the group treated with meloxicam and were mostly resolved in prednisone-treated dogs. However, endoscopic and histological changes were still observed in these two groups after treatment. The severity of all diagnostic features was reduced in the group treated with meloxicam for 3 weeks followed by prednisone for 3 weeks. The significant differences (p < 0.05) were noted between experimental and control groups. The dogs showed a statistically significant reduction in characteristics of the LPR before and after treatment, as measured by clinical signs (Group 1vs.4 p = 0.00, group 2 vs 4 p = 0.00, group 3 vs 4 p = 0,01), by endoscopy (1 vs 4 p = 0,01, 2 vs 4 p = 0,00, 3 vs 4 p = 0,03), and by histopathology (groups 1 vs 4 p = 0,00, 2 vs 4 p = 0,00, 3 vs 4 p = 0,03). The significant differences were noted between experimental groups, as measured by endoscopy (group 2vs 3 p = 0,04), and by relapse rate (groups 1 and 2 p = 0,03, groups 2 and 3 p = 0,01).ConclusionsThe three treatment protocols administered to dogs improved clinical, endoscopic and histological status. However, oral administration of meloxicam for 3 weeks, followed by prednisone for 3 weeks, appeared to be the most successful treatment. These patients remained asymptomatic for 6 months.

Histamine and T helper cytokine–driven epithelial barrier dysfunction in allergic rhinitis

Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and TH2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier. We sought to investigate the role of histamine and TH2 cells in driving epithelial barrier dysfunction in AR. Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested invitro. In addition, the effect of activated TH1 and TH2 cells, mast cells, and neurons was tested invitro. The effect of IL-4, IL-13, IFN-γ, and TNF-α on mucosal permeability was tested invivo. Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity invitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated TH1 and TH2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the TH1- and TH2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ, and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation. Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR.

Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids.

Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). "Mixed rhinitis" (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper-reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.

Nasal compliance measurement for diagnosis of idiopathic non‐allergic rhinitis: A prospective case‐controlled study of 63 patients

• Idiopathic non allergic rhinitis (i-NAR) is a frequent cause of non-allergic rhinitis and associates nonspecific symptoms. There is no simple direct procedure to establish i-NAR diagnosis. • Diagnosis of i-NAR is currently based on an absence of a definite causal factor and a lack of evidence for IgE-mediated allergy by skin prick tests and allergen-specific serum IgE • Measurement of nasal compliance with acoustic rhinometry evaluates the vasomotricity-related deformability of the nasal mucosa. It has been already suggested that nasal compliance could be abnormal in i-NAR. • In this prospective case-controlled study of 42 patients with chronic rhinitis and 21 control patients, after topical decongestion, compliances in i-NAR group were significantly increased compared to allergic rhinitis (AR) and Control group (n=21) (p<0.01). • Measurement of nasal compliance after topical decongestion allows to objectively and non-invasively discriminating i-NAR from AR. This article is protected by copyright. All rights reserved.

Non-allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology.

This EAACI position paper aims at providing a state-of-the-art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called "entopy" or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.

Enhanced chemosensory sensitivity in patients with idiopathic rhinitis and its reversal by nasal capsaicin treatment

The therapeutic action of capsaicin treatment in patients with idiopathic rhinitis (IR) is based on ablation of the transient receptor potential cation channel subfamily V, receptor 1 (TRPV1)-substance P nociceptive signaling pathway. However, the functional consequences of capsaicin treatment on nasal nerve activation and the association between the reduction in nasal hyperreactivity (NHR) and response to capsaicin treatment remain unknown. We sought to study the effects of capsaicin nasal spray on the afferent innervation of the nasal mucosa by monitoring trigeminal nerve activity in patients with IR and healthy control (HC) subjects. A double-blind, placebo-controlled randomized trial with capsaicin nasal spray was performed involving 33 patients with IR and 12 HC subjects. Before and at 4, 12, and 26weeks after treatment, nasal mucosal potentials (NMPs) were measured while exposing the nasal mucosa of patients with IR and HC subjects to aerosols with increasing doses of the chemical irritants allyl isothiocyanate (AITC; also known as mustard oil) or capsaicin. The threshold for each compound was determined for each subject. The results of the NMP measurements were evaluated in parallel with the therapeutic response, visual analog scale scores for nasal symptoms, self-reported NHR, and mRNA expression of PGP9.5; TRPV1; transient receptor potential cation channel subfamily A, receptor 1 (TRPA1); TRPV4; transient receptor potential cation channel subfamily M, member 8 (TRPM8); and nerve growth factor (NGF) in nasal biopsy specimens. AITC turned out to be the best stimulus because the coughing induced by capsaicin interfered with measurements. At baseline, the threshold for evoking changes in NMPs based on AITC was significantly lower for patients with IR compared with HC subjects (P=.0423). Capsaicin treatment of IR patients increased the threshold for the response to AITC at 4 and 12weeks compared with placebo (P=.0406 and P=.0325, respectively), which returned to baseline by week 26 (P=.0611). This increase correlated with changes in visual analog scale major symptom (P=.0004) and total symptom (P=.0018) scores. IR patients with self-reported NHR at baseline showed a trend to being better responders to capsaicin treatment compared with patients with IR but without NHR (P=.10). The lower threshold for AITC based on NMPs in patients with IR compared with HC subjects and the increased threshold for AITC after capsaicin treatment in patients with IR demonstrate the crucial role of TRPA1 and TRPV1 in IR pathophysiology. The strong correlation between the increase in AITC threshold in patients with IR and symptom reduction after capsaicin treatment demonstrates the clinical relevance of these findings.

Severity of Nasal Inflammatory Disease Questionnaire for Canine Idiopathic Rhinitis Control: Instrument Development and Initial Validity Evidence.

BackgroundEffective treatments are needed for idiopathic chronic rhinitis in dogs, but assessment of efficacy requires a practical, quantifiable method for assessing severity of disease.ObjectivesTo develop and perform initial validity and reliability testing of an owner‐completed questionnaire for assessing clinical signs and dog and owner quality of life (QOL) in canine chronic rhinitis.AnimalsTwenty‐two dogs with histopathologically confirmed chronic rhinitis and 72 healthy dogs.MethodsIn this prospective study, an online questionnaire was created based on literature review and feedback from veterinarians, veterinary internists with respiratory expertise, and owners of dogs with rhinitis. Owners of affected dogs completed the questionnaire twice, 1 week apart, to test reliability. Healthy dogs were assessed once. Data were analyzed using the Rasch Rating Scale Model, and results were interpreted using Messick's framework for evaluating construct validity evidence.ResultsInitial item generation resulted in 5 domains: nasal signs, paranasal signs, global rhinitis severity, and dog's and owner's QOL. A 25‐item questionnaire was developed using 5‐point Likert‐type scales. No respondent found the questionnaire difficult to complete. Strong psychometric evidence was available to support the substantive, generalizability, content, and structural aspects of construct validity. Statistical differences were found between responses for affected and control dogs for all but 2 items. These items were eliminated, resulting in the 23‐item Severity of Nasal Inflammatory Disease (SNIFLD) questionnaire.Conclusions and Clinical ImportanceThe SNIFLD questionnaire provides a mechanism for repeated assessments of disease severity in dogs with chronic rhinitis.

Pathogenesis of rhinitis.

Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called idiopathic (previously 'vasomotor') rhinitis. Allergic rhinitis affects approximately one in four of the population of westernized countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptive immunity together with environmental factors is likely to play major roles. In allergic rhinitis, initial allergen exposure and sensitization involves antigen-presenting cells, T and B lymphocytes and results in the generation of allergen-specific T cells and allergen-specific IgE antibodies. On re-exposure to relevant allergens, cross-linking of IgE on mast cells results in the release of mediators of hypersensitivity such as histamine and immediate nasal symptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 T lymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phase allergic response. Evidence for nasal priming and whether or not remodelling may be a feature of allergic rhinitis will be reviewed. The occurrence of so-called local allergic rhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE-mediated) rhinitis will be considered in the context of inflammatory and non-inflammatory disorders.

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.

Botulinum Toxin for Rhinitis.

Rhinitis is a common clinical entity. Besides nasal obstruction, itching, and sneezing, one of the most important symptoms of rhinitis is nasal hypersecretion produced by nasal glands and exudate from the nasal vascular bed. Allergic rhinitis is an IgE-mediated inflammatory reaction of nasal mucosa after exposure to environmental allergens. Idiopathic rhinitis describes rhinitis symptoms that occur after non-allergic, noninfectious irritants. Specific allergen avoidance, topical nasal decongestants, nasal corticosteroids, immunotherapy, and sinonasal surgery are the main treatment options. Because the current treatment modalities are not enough for reducing rhinorrhea in some patients, novel treatment options are required to solve this problem. Botulinum toxin is an exotoxin generated by Clostridium botulinum. It disturbs the signal transmission at the neuromuscular and neuroglandular junction by inhibiting the acetylcholine release from the presynaptic nerve terminal. It has been widely used in neuromuscular, hypersecretory, and autonomic nerve system disorders. There have been a lot of published articles concerning the effect of this toxin on rhinitis symptoms. Based on the results of these reports, intranasal botulinum toxin A administration appears to be a safe and effective treatment method for decreasing rhinitis symptoms in rhinitis patients with a long-lasting effect. Botulinum toxin type A will be a good treatment option for the chronic rhinitis patients who are resistant to other treatment methods.

Treatment of idiopathic rhinitis with kinetic oscillations – a multi-centre randomized controlled study

Conclusions: The potential effects of KOS are still uncertain regarding the most effective air pressure to be used as well as the physiological effects on the nasal mucosa. The results of the study do not support a convincing treatment effect by KOS on IR. Objectives: Idiopathic rhinitis (IR) is a common disorder, affecting ∼10–20% of the population. A new method for treating IR, Kinetic Oscillation Stimulation (KOS), has been reported to have beneficial effects on total vasomotor symptom scores (TVRSS). The primary objective with this study was to evaluate if a mean pressure of 65 mbar, pressure amplitude of 100 mbar, and 68 Hz treatment with KOS had a positive effect on total vasomotor symptom scores (TVRSS), as compared with a mean pressure of 65 mbar, pressure amplitude of 4 mbar, and 68 Hz treatment in patients with idiopathic rhinitis. Methods: Two hundred and seven patients were randomized (Full Analysis Set, FAS) in the study, including five visits and lasting for ∼25 weeks. All patients had two treatment episodes, and all patients had at least one treatment, meant as active, with high amplitude pressure for 10 min in each nostril. Group 1 had two such treatments, and Group 2 had one treatment with low amplitude pressure, initially meant as placebo, on one occasion. Because of numerical improvements in these two groups, a new control group, Group 3, was introduced. They had one new control treatment where the balloon was inserted into the nose, without any air inflation and without oscillations. Results: KOS treatment with high amplitude pressure did not have significant beneficial effects as compared to low amplitude pressure on TVRSS. Numerical improvements in TVRSS and SNOT 22 were found when comparing high and low amplitude pressure treatments with uninflated balloon treatment. However, this part of the study was initially single-blinded, and these results were secondary objectives.

The importance of mold sensitivity in nonallergic rhinitis patients.

In recent studies, local specific immunoglobulin E (sIgE) production against allergens in nasal mucosa and a positive response to a nasal allergen provocation test (NAPT) have been demonstrated in some patients initially diagnosed as nonallergic rhinitis (NAR) or idiopathic rhinitis (IR). The aim of this study was to evaluate the presence of local allergic rhinitis (LAR) in patients who experience rhinitis symptoms in indoor and outdoor moldy conditions and to investigate the role of the NAPT in diagnosis. A total of 40 NAR patients with a history of persistent rhinitis and who had negative skin-prick tests (SPTs) and serum sIgE levels to common aeroallergens, as well as 20 healthy subjects were included in the study. NAPTs were performed with Aspergillus fumigatus (group 1) or a mixture of Alternaria alternata and Cladosporium herbarum extracts (group 2). In patient nasal lavage fluids, tryptase and mold sIgE levels were not significantly different from the control group. NAPT with Aspergillus fumigatus was positive in 8 of 12 NAR patients (66.6%) in group 1 and NAPT with the mixture of extracts was positive in 9 of 13 NAR patients (69.2%) in group 2. This study suggests that LAR may exist in a significant number of the persistent rhinitis patients who were previously considered as NAR based on negative SPTs or serum sIgE tests. To the best of our knowledge, this is the first study evaluating a nasal local allergic response to both indoor and outdoor molds.

Non-allergic Rhinitis: Epidemiology, Diagnostic and Therapy

Non-allergic rhinitis is a heterogenous group of medical diseases without an IgE-mediated pathophysiology. In this review, typical subgroups are presented with data regarding their frequency, clinical symptoms and recommendations for an effective and efficient diagnostic and therapeutic approach are indicated. The most common subtype is the non-allergic rhinopathy, also known as idiopathic or vasomotoric rhinitis. Because medication induced rhinitis is still a frequent clinical problem, a step wise approach to wean the patient is presented.

Non-IgE-Mediated Rhinitis

Patients with chronic rhinitis symptoms frequently present in physicians’ offices. The best-studied form of chronic rhinitis is IgE-mediated allergic rhinitis; however, the prevalence of non-allergic, non-IgE-mediated rhinitis among the chronic rhinitis population is high, and the disorder is an important cause of widespread morbidity. Despite this fact, almost no diagnostic tests or adjusted treatment schedules are established for this patient group. Chronic non-IgE-mediated rhinitis covers an extensive range of different diagnoses and comprises drug-induced, hormonal, occupational, gustatory, senile, and idiopathic rhinitis. The etiology as well as pathophysiology is only defined for some of these forms. This review summarizes the causes of non-IgE-mediated rhinitis as well as the available options for diagnostic work-up and treatment strategies. It aims at providing a tool for a more individual approach of non-allergic rhinitis patients in order to obtain an improvement of their quality of life.

Capsaicin for non-allergic rhinitis.

There are many forms of rhinitis. Patients are diagnosed with non-allergic rhinitis when anatomic, infectious and allergic aetiologies have been excluded. The symptoms, including nasal congestion, blockage or obstruction, clear rhinorrhoea, sneezing and, less frequently, nasal itching, can range from mild to debilitating. It affects between 25% and 50% of patients with rhinitis. Several medications are widely used in the treatment of non-allergic rhinitis, including oral and topical nasal antihistamines, intranasal and (rarely) systemic corticosteroids, and anticholinergics. Capsaicin, the active component of chili peppers, delivered intranasally, is considered a treatment option for non-allergic rhinitis. To assess the effectiveness of capsaicin in the management of non-allergic rhinitis compared with no therapy, placebo or other topical or systemic medications, or two or more of the above therapies in combination, or different capsaicin regimens. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 24 June 2015. Randomised controlled trials in adult patients with non-allergic rhinitis comparing intranasal capsaicin with no therapy, placebo or other topical or systemic medications, or their combinations. We used the standard methodological procedures expected by The Cochrane Collaboration. We included four studies (five publications) involving 302 participants with idiopathic non-allergic rhinitis. All the included studies described patients with moderately severe, idiopathic non-allergic rhinitis who were between the ages of 16 and 65. Studies had follow-up periods ranging from four to 38 weeks. The overall risk of bias in the studies was either high or unclear (two studies had overall high risk of bias, while two others had low to unclear risk of bias). Using the GRADE system we assessed the evidence as being of low to moderate quality. A meta-analysis was not possible, given lack of similarity of the reported outcomes.Two studies compared capsaicin with placebo. One study reported that capsaicin resulted in an improvement of overall nasal symptoms (a primary outcome) measured on a visual analogue scale (VAS) of 0 to 10. There was a mean difference (MD) of -3.34 (95% confidence interval (CI) -5.24 to -1.44), MD -3.73 (95% CI -5.45 to -2.01) and MD -3.52 (95% CI -5.55 to -1.48) at two, 12 and 36 weeks post-treatment, respectively. Another study reported that, compared to placebo, capsaicin (at 4 µg/puff) was more likely to produce overall symptom resolution (reduction in nasal blockage, sneezing/itching/coughing and nasal secretion measured with a daily record chart) at four weeks post-treatment (a primary outcome). The risk ratio (RR) was 3.17 (95% CI 1.38 to 7.29).One study compared capsaicin to budesonide (an intranasal corticosteroid). This study found that patients treated with capsaicin had a better overall symptom score compared to those treated with budesonide (MD 2.50, 95% CI 1.06 to 3.94, VAS of 0 to 10). However, there were no differences in the individual symptom scores for headache, postnasal drip, rhinorrhoea, nasal blockage, sneezing and sore throat assessed during the last three days of a four-week treatment.One study compared two different regimens of capsaicin administration: five treatments in one day versus five treatments given every two to three days during two weeks. Using daily record charts, the study reported significant improvement of individual symptom scores for rhinorrhoea in patients treated five times per day, however numerical data were not presented. There were no improvements in the other outcomes: rhinorrhoea, nasal obstruction, sneezing and overall nasal symptoms, measured on a VAS.Finally, one of these studies also compared three doses of capsaicin (to placebo). Patients treated with a 1 µg versus 4 µg per puff dose of capsaicin had a worse daily record chart overall symptom score resolution (RR 0.63, 95% CI 0.34 to 1.16).Only one study attempted to measure adverse effects (a primary outcome), however due to methodological issues with the assessment we are unable to draw any conclusions.We sought to include other secondary outcomes (e.g. quality of life measures, treatment dropouts, endoscopic scores, turbinate or mucosal size, cost of therapy), but none of these were measured or reported in the included studies. Capsaicin may be an option in the treatment of idiopathic non-allergic rhinitis. It is given in the form of brief treatments, usually during the same day. It appears to have beneficial effects on overall nasal symptoms up to 36 weeks after treatment, based on a few, small studies (low-quality evidence). Well-conducted randomised controlled trials are required to further advance our understanding of the effectiveness of capsaicin in non-allergic rhinitis, especially in patients with non-allergic rhinitis of different types and severity, and using different methods of capsaicin application.

Effect of Botulinum Neurotoxin A Injection into the Submucoperichondrium of the Nasal Septum in Reducing Idiopathic Non-Allergic Rhinitis and Persistent Allergic Rhinitis.

Submucoperichondrial injection of botulinum neurotoxin A (BTA) in the nasal septum is a promising therapeutic option in the treatment of persistent allergic rhinitis (AR) and non-allergic rhinitis, and is safer and more effective than intraturbinate injection in reducing clinical symptoms. Forty patients diagnosed with persistent AR or non-allergic rhinitis referred to Shafa Medical Center affiliated to Kerman University of Medical Sciences were included in this study and were randomly allocated to the intervention or control groups. Patients received an injection of 80 units BTA (Dysport, Ipsen Ltd Company, UK) at a concentration of 200 mU/ml in normal saline on four spots in each side of the nose and were followed for 12 weeks. Data were analyzed using a chi-square or Fisher's test, and Mann Whitney U test. The mean age of patients was 46.1±15.3 years, and the two groups did not differ significantly in demographic variables. The severity of rhinitis symptoms was reduced after 4 weeks of injections in the intervention group and then gradually decreased further until the 12th week. There was a statistically significant difference between the groups (P<0.05). No adverse effects were reported. Submucoperichondrial BTA injection can be considered an effective therapeutic option in patients with persistent AR and idiopathic rhinitis. In comparison with other injection techniques, submucoperichondrial BTA injection has fewer side effects with a longer period of effectiveness, and is easy to perform and is more tolerable for the patient.

Idiopathic lymphoplasmacytic rhinitis in 33 dogs.

Idiopathic lymphoplasmacytic rhinitis (LPR) is recognised frequently in dogs with clinical signs typical of other chronic nasal diseases. The purpose of this study was to determine clinical signs, survey radiographic, rhinoscopic and histologic abnormalities and the response to therapy in dogs with LPR. It was a retrospective study of 33 client-owned animals of various breeds and ages that had been diagnosed with LPR. During the study period, a total of 110 dogs were diagnosed with nasal disease, of which 33 (30%) were diagnosed with idiopathic LPR. The median age was 9 years (range 2.3-17 years) and there were 15 female and 18 male dogs. The majority of dogs showed a mucoid nasal discharge, bilateral stertor and no overt radiographic changes. The most common finding on rhinos copy was hyperaemic nasal mucous membranes with mucoid material accumulation within the nasal cavity. In all 33 dogs bacterial culture yielded no pathogenic bacteria and fungal culture was negative. Histologically, all 33 dogs showed lymphoplasmacytic infiltration within the nasal mucosa. All 33 dogs were treated with systemic and topical corticosteroids for varying lengths of time and dosing intervals. Eleven dogs were treated with concurrent cyclosporine and three dogs underwent allergy testing followed by desensitisation therapy. The best response was seen in the dogs that underwent desensitisation therapy, followed by those treated with corticosteroids and cyclosporine.