Nonallergic Rhinitis

Abstract

Non-allergic rhinitis (NAR) is a heterogeneous nasal disease with high global prevalence. While the specific factors contributing to the origin of NAR remain uncertain, there is indication that neurogenic factors play a significant role in the development of NAR. There are seven subtypes with overlapping presentations, including senile or geriatric rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal rhinitis, smokers’ rhinitis, occupational rhinitis and idiopathic rhinitis. The approach to treatment is focused on alleviating symptoms and parallels the methods used for allergic rhinitis. Patients are advised to minimize exposure to identified triggers whenever feasible. Initial treatments involve the use of primary interventions such as intranasal corticosteroids, intranasal antihistamines, and intranasal ipratropium. Combination therapies may be considered if single interventions do not effectively manage symptoms. The surgery is considered in patients refractory to medical therapy, the reduction of inferior turbinate hypertrophy is a surgical procedure with an excellent outcome, besides the selective neurectomy of the vidian branches, has also proven to be effective.

1. Introduction

Rhinitis constitutes an alteration of the nasal mucosa and stands out as one of the prevalent reasons for medical consultations globally. Its incidence has shown a rising trend over time. This condition is notably widespread in both Europe and America, with geographical variations possibly attributed to diverse environmental conditions, lifestyle factors, and host-related risk factors [1, 2].

The classification of rhinitis includes infectious rhinitis, allergic rhinitis, non-allergic rhinitis, and mixed rhinitis. Although non-allergic and allergic rhinitis exhibit certain overlapping symptoms, they diverge in terms of treatment approaches, affected demographic groups, and underlying pathophysiology [2]. Figure 1 shows the phenotypes of chronic rhinitis.

Figure 1.

Phenotypes of chronic rhinitis.

Infectious rhinitis, as its name implies, is a condition triggered primarily by a virus, and to a lesser proportion, by bacteria, commonly recognized as the common cold. Symptoms encompass the presence of discolored nasal secretions, nasal obstruction or congestion, and the formation of crusts [3].

Allergic rhinitis is caused by IgE mediated reactions to inhaled allergens that trigger a type 2 immune reaction that starts in childhood and usually have seasonal exacerbation of symptoms. It is associated to asthma and conjunctivitis. Treatment included allergen avoidance, topic corticosteroid, antihistamines, and immunotherapy [2, 4].

Nonallergic rhinitis is a chronic condition that starts later in life which is defined as inflammation or dysfunction of the nasal mucosa present for at least 12 weeks per year without any indications of allergic sensitization. Diagnostic tests capable of detecting allergies include allergic skin tests, measurement of total immunoglobulin E (IgE), and specific serum IgE assays for certain allergens [1, 3, 5].

To establish a diagnosis of chronic rhinitis, it is necessary for two nasal symptoms to be consistently present for at least 1 hour each day. These symptoms include rhinorrhea (anterior or posterior), nasal obstruction or congestion, sneezing or nasal itch, cough, hyposmia, facial pressure, and eustachian tube dysfunction. These symptoms can be categorized as perennial/persistent, intermittent, or triggered by non-immunologic factors such as irritants, environmental humidity, or temperature variations [3, 5, 6, 7].

Mixed rhinitis has the characteristic of presenting several etiologic factors, whether known or not, that is why the diagnostic must be precise and a nasal endoscopy should be done to identify the presence of chronic rhinosinusitis with or without polyps and anatomic factors that may increase symptoms and are completely different pathologies [3].

2. Epidemiology

Limited data are available regarding the prevalence of general rhinitis, with even fewer statistics on Nonallergic rhinitis. However, estimates indicate that over 70 million individuals in the United States and 200 million globally are affected by chronic rhinitis. The European Community Respiratory Heath Survey (ECRHS), the most extensive international multicenter study on prevalence, reported a median self-reported nasal allergy prevalence of 20.9% in 1995, focusing on Western European countries. Notably, it did not delineate the prevalence of Nonallergic or allergic rhinitis. The absence of prevalence data for nonallergic rhinitis is attributed to the lack of a standardized definition and diagnostic criteria, as highlighted by Hellings. Nonetheless, Greiwe et al. proposed mechanistic theories involving autonomic dysfunction, resulting in altered sympathetic activity or parasympathetic overactivity. These mechanisms also encompass changes in the expression of receptor potential channels on sensory nerves in the nasal mucosa, serving as irritant sensors, and the involvement of neuropeptides leading to vasodilation and transudation [3, 7, 8].

Savoure et al. perform a study of worldwide prevalence of rhinitis and described unspecified rhinitis prevalence at 29.4% (1.1 to 63.3%), allergic rhinitis with 18.1% (1 to 54.5%) and 12% for nonallergic rhinitis (4 to 31.4%). They classified the median prevalence based on symptoms at 16.4% and based on IgE definition at 31.4% for nonallergic rhinitis. Bernstein et al., reported prevalence of 23, 34 and 43% for nonallergic rhinitis, mixed rhinitis, and allergic rhinitis respectively [7].

Between the prevalence reported Savoure et al. found studies from Europe, Africa, Asia, Oceania and America for non-specific rhinitis and allergic rhinitis but there were no data from America, Africa, and Oceania for nonallergic rhinitis. For Asia reported prevalence were ranging from 4 to 31.4% and for Europe 5.5 to 23.5% [9].

Savoure et al. in another study reported general prevalence of rhinitis were 53.4%, allergic rhinitis 36.5% and nonallergic rhinitis 16.9% and the onset of allergic rhinitis were 10 years earlier compared with nonallergic rhinitis which is consistent with Dykewicz that explain a study perform by Rondon et al. in which compared nonallergic and allergic rhinitis and demonstrated that patients with nonallergic rhinitis tend to be older and have severe symptoms and unlikely association to asthma. Savoure et al. reported in their study that moderate to severe rhinitis was found in higher percentage in nonallergic rhinitis (40%) compared with allergic rhinitis (24%) [1, 2].

Dykewicz et al. estimated nonallergic rhinitis affect 17–52% of adults in the United States and 34% may have a mixed rhinitis [1].

An important difference between nonallergic and allergic rhinitis is the seasonality of symptoms. Savoure et al. referred allergic rhinitis increased from March to June (spring) and nonallergic rhinitis increased during winter and decreases from May to September which is demonstrated in Figure 2 [2].

Figure 2.

Seasonality of symptoms of nonallergic rhinitis (NAR) and allergic rhinitis (AR) [2].

3. Histopathology of allergic rhinitis and non-allergic rhinitis

In the inflammatory process of rhinitis, the hair cells decrease and the number of goblet cells responsible for: rhinorrhea increased; capillary permeability causing edema and nasal obstruction [10], with stimulation of nerve endings responsible for sneezing and neuromodulators that recruit more inflammatory cells [11]. Chronic hypertrophic is characteristic with loss of cilia and a tendency to squamous metaplasia [12].

In their research, Ríos et al. discovered that histological examination of allergic rhinitis revealed a noteworthy increase in remodeling across all patterns, including epithelial markers and edema, except for fibrosis. Within the stromal marker, there was an elevated occurrence of subepithelial edema, and this was directly proportional to the presence of more than 10 eosinophils per field. This finding is clinically associated with heightened obstruction and severity of the condition [13].

Fibrosis was more frequently identified in the non-allergic variant, although this observation did not reach statistical significance. The collagen deposition in these cases is influenced by the upregulation of transforming growth factor beta [14].

3.1 Non-allergic rhinitis phenotypes

NAR needs to be differentiated from rhinitis patients experiencing an allergic response localized to the nasal mucosa, which is commonly referred to as local allergic rhinitis (LAR) [3]. NAR is characterized by rhinorrhea, blocked nose, sneezing, and/or itchy nose without clinical signs of infection or allergy. Figure 3 shows the subtypes of non-allergic rhinitis [12].

Figure 3.

Diagnosis of chronic rhinitis [3].

Nonallergic noninfectious rhinitis (NANIR) encompasses a diverse set of patients experiencing rhinitis without apparent signs of infection, such as discolored secretions, and lacking systemic indications of allergic inflammation, such as allergen-specific IgE in the blood. Subcategories within NAR include drug-induced rhinitis, rhinitis associated with aging, hormonal rhinitis, including pregnancy-induced rhinitis, nonallergic occupational rhinitis, gustatory rhinitis, and idiopathic rhinitis [15, 16, 17, 18]; its phenotyping is essential for choosing the best treatment option [19, 20].

3.1.1 Subgroups of NAR

3.1.1.1 Senile rhinitis or rhinitis

Senile rhinitis or rhinitis in elderly is characterized as rhinitis occurring in individuals aged 65 years and older, constituting an often-overlooked condition that impacts up to 29.8% of the population in this age group. The diagnosis of senile rhinitis typically pertains to individuals experiencing bilateral watery nasal secretions in the absence of endonasal mucosal or anatomical abnormalities. The symptoms are attributed to neurogenic dysregulation and are considered to arise late in onset [9].

3.1.1.2 Gustatory rhinitis

Is marked by a runny nose following the consumption of hot and spicy foods. This phenomenon is thought to be triggered by a gustatory reflex linked to an overactive neural system that is nonadrenergic, noncholinergic, or peptidergic [9].

3.1.1.3 Occupational rhinitis

Is characterized as inflammation of the nasal mucosa resulting from exposure to a specific work environment and must be differentiated from “work-exacerbated” rhinitis [6]. Substances linked to occupational rhinitis include allergens of both high and low molecular weight (HMW and LMW) as well as irritants, according to reports. HMW agents could trigger a typical allergic inflammation mediated by IgE. The mechanisms behind chronic inflammation caused by LMW molecules are not clearly understood [9].

Prolonged exposure to occupational agents may lead to the development of asthma in patients. Recognizing occupational rhinitis is crucial for preventing occupational asthma. Rhinitis can emerge anew following prolonged exposure to airborne irritant chemicals in the occupational or environmental setting [20].

Nasal hyperreactivity to workplace triggers that are not specifically identified can also exist, with only about one-third of individuals experiencing relief during weekends or vacations. Individuals reported that their nasal issues were linked to sensitivity to nonspecific workplace triggers like air conditioning, dust and dry air [9, 12].

3.1.1.4 Hormonal rhinitis

Hormonal imbalances occurring during various stages such as the menstrual cycle, puberty, pregnancy, menopause, and specific endocrine disorders like hypothyroidism and acromegaly are frequently linked to NAR. Estrogens, induce nasal vascular engorgement, potentially leading to nasal obstruction and/or increased nasal secretions. Both beta-estradiol and progesterone contribute to an elevated expression of histamine H1-receptors on the nasal epithelium. Although hormonal changes are believed to have a notable impact, especially in conditions such as gestational rhinitis or pregnancy-induced rhinitis, the exact pathophysiology of hormonal rhinitis remains uncertain.

Smoking emerges as the sole universally acknowledged risk factor in pregnancy-induced rhinitis [12]. Regarding instances of new-onset allergic rhinitis and asthma after puberty, studies suggest that girls undergoing a delayed onset of menarche (first menstruation) are less susceptible to developing allergic rhinitis compared to those experiencing menarche at the average age.

Late menarche (occurring after 13 years of age) is statistically inversely correlated with the development of allergic rhinitis [9].

Additionally, the use of hormonal contraceptives is inversely associated with the onset of allergic rhinitis, suggesting that, aside from endogenous hormones, these contraceptives might provide protection against allergies and asthma in young women post-puberty [20].

3.1.1.5 Drug-induced rhinitis

A variety of drugs may cause nasal symptoms, primarily nasal obstruction. 11 Nasal obstruction and post-nasal drip being the most prominent complaints. Drug-induced rhinitis can be divided into two subgroups:

• adverse events of systemic treatment: includes prolonged oral intake of aspirin, ibuprofen, and other NSAID, beta-blockers, sedatives, antidepressants, oral contraceptives, or drugs used to treat erectile dysfunction. Peptidergic drugs activate human mast cells through a G-protein coupled receptor, and this interaction could be responsible for some forms of drug-induced rhinitis

• abuse of decongestive nasal therapy, most commonly recognized as rhinitis medicamentosa (RM), this condition arises from the extended use of powerful decongestant sprays, and it is advised to discontinue the use of these sprays suddenly [14].

Rhinitis medicamentosa (RM) is a result of a particular medication with localized action, operating through a distinct pathophysiological mechanism and showing connections with psychiatric conditions like anxiety or opioid use disorders. Mehuys et al. have revealed concerning rates of nasal decongestant (ND) abuse. Approximately half of individuals with persistent rhinitis, obtaining over-the-counter medication for their nasal issues, were found to be overusing ND, despite being informed about the recommended duration of use [21].

3.1.1.6 Smokers’ rhinitis

Current smokers exhibited a significantly higher likelihood of having NAR compared to non-smokers (chi-square p = .034, OR 1.7 (1.04–2.8); RR 1.6 (1.004–2.6)). Among the NAR group, current smokers had a notably higher number of pack-years of smoking in comparison to individuals who were currently smoking but did not have NAR (32 ± 29 vs. 14 ± 14; t-test p = .014; MWU test p = .04) [20].

In contrast, former smokers had a comparable likelihood of having NAR when compared to those who had never smoked. The pack/year of smoking among former smokers did not differ between those with NAR and the control group [20].

3.1.1.7 Idiopathic rhinitis

Approximately half of individuals with NAR lack a clearly defined cause for their symptoms and are referred to as idiopathic rhinitis patients. The defining characteristic of these patients is the presence of Nasal Hyperreactivity. Recently, research has demonstrated an upregulation of the nociceptive TRPV1-substance P (SP) signaling pathway in idiopathic rhinitis patients, suggesting its probable involvement in the pathophysiology [2].

In her research, Klementina et al. affirms that Idiopathic Rhinitis (IR) represented the highest prevalence among the phenotypes, accounting for 39% of the NAR group. IR is characterized as a purely neurogenic phenotype, and identifying the disease with NHR as its most prominent symptom holds significant implications for its treatment [2].

Additionally, Klementina notes that 20% of the Non-Allergic Rhinitis group defied classification into any of the defined phenotypes. In this subset, a discernible pattern explaining the nature of nasal complaints eluded identification. Without NHR as a defining criterion for IR, these individuals might have been categorized under IR. This subgroup potentially comprises participants with anatomical factors contributing to nasal symptoms, such as septal deviation and/or inferior turbinate hypertrophy, and/or phenotypes that are yet to be recognized [20].

3.2 Diagnosis

The diagnosis of NAR relies on a comprehensive medical history, which includes the exclusion of clinically relevant sensitization to airborne allergens and the absence of clinical signs of rhinosinusitis [22]. In addition to the medical history, anterior rhinoscopy is employed to examine for signs of infection, endonasal crust formation, and/or significant anatomical deformities.

Nasal endoscopy is strongly recommended, as it enables a comprehensive evaluation of the entire endonasal cavity, including the ostiomeatal complex. Emphasizing the significance of nasal endoscopy in diagnosing prolonged cases of rhinitis is crucial, as it can unveil the presence of chronic rhinosinusitis without nasal polyps (CRSsNP) or with nasal polyps (CRSwNP) [21, 22].

The following diagnostic tests are not recommended in NAR: allergen provocation testing, microbiological analysis of the nasal content, nasal cytology or biopsies, measurement of total IgE or allergen-specific IgE in nasal secretions, CT scans of the sinonasal cavities, measurement of nasal hyperreactivity, measurement of markers of cerebrospinal fluid leakage (b2- transferrin or b-trace [21]. Figure 4 shows an algorithm for diagnosis between the subtypes [20].

Figure 4.

Definitions of NAR phenotypes. NHR – Nasal hyper reactivity [20].

4. Endotypes of NAR

Varieties exist with diverse pathophysiological mechanisms, broadly categorized into a traditional inflammatory pathway, a neurogenic pathway, and other pathways that are predominantly unknown (Figure 5) [20].

Figure 5.

Endotype and phenotype of NAR [20].

The inflammatory pathway is present in a subset of NAR individuals. A Th2 cytokine inflammatory pattern, observed in patients with Allergic Rhinitis (AR) and those with work-related allergic rhinitis triggered by high molecular weight (HMW) allergens, characterizes this subgroup. Managing these patients typically poses no significant therapeutic challenges, as they generally respond favorably to nasal corticosteroid treatment, akin to individuals with Local Allergic Rhinitis (LAR) [20, 22].

Nevertheless, a portion of Non-Allergic Rhinitis (NAR) patients does not exhibit an infiltration of inflammatory cells in the nasal mucosa, suggesting involvement of a neurogenic mechanism. This includes conditions such as rhinitis of the elderly, gustatory rhinitis, certain types of occupational rhinitis, certain drug-induced rhinitis, and Idiopathic Rhinitis (IR). The intricate neural regulation of the upper airways involves various interacting nervous systems, where sensory, parasympathetic, and sympathetic nerves play roles in regulating processes in the nasal mucosa, including epithelial, vascular, and glandular functions [20, 21, 22].

Certain phenotypes appear to stem from a relatively straightforward regulatory disorder. For instance, rhinitis of the elderly primarily appears to involve a dysregulation in the balance between the parasympathetic and sympathetic neural systems. This can be addressed with the anticholinergic drug ipratropium bromide. Another example is rhinitis medicamentosa, where dysregulation of adrenergic receptors in the nasal mucosa results in a relative increase in parasympathetic drive, causing significant rhinorrhea and nasal obstruction [20].

Specialized epithelial chemosensors known as solitary chemosensory cells in the nasal cavity react to irritants via the canonical taste transduction cascade, activating peptidergic trigeminal nociceptive (pain) nerve fibers. The activation of these nasal cells can initiate comparable local inflammatory responses, including mast cell degranulation and plasma leakage. This response mirrors the effects of directly exciting trigeminal pain fibers using capsaicin. Importantly, this reaction is solely attributable to cholinergic neurotransmission and neural activity, without involving the release of local inflammatory mediators.

Idiopathic Rhinitis is believed to be a disorder affecting the nonadrenergic noncholinergic (NANC) or peptidergic neural system. Perivascular and intraepithelial nonadrenergic noncholinergic (NANC) sensory nerve fibers contain neuropeptides, including VIP, substance P (SP), and calcitonin gene-related peptide (CGRP). These neuropeptides are locally released from peptidergic neurons, mainly unmyelinated sensory C-fibers, in the nasal mucosa following activation by nonspecific stimuli. They can be responsible for the symptoms of IR. Stimulation may occur due to inflammatory mediators like histamine and bradykinin, as well as various inhaled irritants such as nicotine, chlorine, formaldehyde, and capsaicin, predominantly acting via the TRPA1 and TRPV1 receptors. Recent findings indicate an upregulation of the nociceptive TRPV1-SP signaling pathway in individuals with IR [18, 19, 20].

5. Treatment of NAR

Patients diagnosed with NAR are often offered different treatment modalities ranging from nasal topical medication to surgical [23].

The treatment modalities includes trigger avoidance, topical and systemic medications, and surgery [24, 25, 26, 27].

There is little systematization in the protocols and there is little high-grade evidence regarding treatment, which causes difficult management with an impact on the quality of life and low patient satisfaction [23].

Intranasal corticosteroids are the first choice for NAR. Intranasal antihistamines have also been used in combination with the intranasal corticosteroids when monotherapy could not adequately control the symptoms of NAR [21].

5.1 Treatment modality

5.1.1 Intranasal corticosteroids

Act locally on the nasal mucosa, eliciting anti-inflammatory and immunosuppressant effects, modifying and reducing inflammation through suppression of the synthesis of pro-inflammatory cytokines and proinflammatory enzymes, inhibiting lymphocyte proliferation and chemotaxis [24, 25]. Avoid the systemic side effects of corticosteroids [25].

First-generation intranasal corticosteroids:

• Beclomethasone dipropionate

• Triamcinolone acetonide

• Flunisolide

• Budesonide

Second-generation intranasal corticosteroids:

• Fluticasone furoate

• Fluticasone propionate

• Mometasone furoate

• Betamethasone sodium phosphate

• Ciclesonide

Fluticasone propionate and beclomethasone dipropionate are the only topical nasal corticosteroids approved by the Food and Drug Administration for treatment of NAR [26, 27].

The adverse effects are [25]:

• Epistaxis (5–10%)

• Nasal irritation (5–10%, including dryness, burning and stinging)

• Headache

• Nasal septal perforation (<1%)

• Candida infection of the nose and pharynx

• Impaired wound healing after recent nasal surgery or trauma.

Intranasal corticosteroids are likely to work better for the inflammatory endotypes of non-allergic rhinitis [25].

The certainty of the evidence for most outcomes in this review was low or very low. Not all studies have shown these agents to be effective [25, 26].

It is unclear whether intranasal corticosteroids reduce patient-reported disease severity in non- allergic rhinitis patients compared with placebo when measured at up to 3 months. There is a lack of evidence comparing intranasal corticosteroids with other pharmacological treatments [23, 27].

It is unclear which is the best intranasal corticosteroid to use with respect to type, concentration, vehicle and how often to use it [25, 27].

5.1.2 Combination of intranasal corticosteroids antihistamines

Combination therapy of fluticasone propionate and azelastine hydrocholoride (AZE) – first-line therapies in seasonal allergic rhinitis – has been shown to be more effective compared against monotherapy with either class or placebo in seasonal allergic rhinitis [25, 27].

Combination therapy can be achieved either by using 2 separate nasal sprays or a combination product [27].

5.1.2.1 Topical antihistamine

Unclear mechanism(s) of action in since this is a non immunoglobulin E pathophysiology.

To diminish eosinophil activation and adhesion molecule expression and suppression of inflammatory cytokine generation [27].

Two topical antihistamine sprays have been studied in NAR, azelastine and olopatadine [23, 27].

Olopatadine and azelastine (0.1%) were compared for the treatment of NAR in a multicenter, randomized, both reduced congestion, rhinorrhea, postnasal drip, and sneezing; There were no statistically significant differences between their effects [23, 27].

In the review by Khoueir et al., all studies used Azelastine Hydrochloride (HCl) (137 mcg/aerosol) vs. olopatadine HCl 0.6% (665 mcg/spray). Both groups showed an importance decrease in TNSS after 14 days of treatment (p < 0.001) [23].

A statistically significant adverse effect reported was the sensation of bitter taste in patients who used azelastine. Another adverse effect reported in 3 studies was minor nasal bleeding [23].

5.1.2.2 Ipratropium bromide

The ipratropium bromide is the only topical anticholinergic approved in the treatment of NAR [24, 26]. In a study of 253 patients with perennial NAR the ipratropium nasal spray significantly reduced rhinorrhea versus placebo [16, 19]; dryness and epistaxis were uncommon [25].

5.1.2.3 Topical capsaicin

Reduced the density of the innervation of the nasal mucosa and the TRPV1-SP signaling pathway, without affecting the integrity and function of nasal epithelial cells or mast cells [24].

5.1.2.4 Oral decongestants

There is a lack of good evidence of effect, but theoretically it may be helpful for nasal stuffiness only [25].

5.1.2.5 Oral antihistamines

Limited data suggest that the newer nonsedating H1 antihistamines are not as effective in NAR, compared with allergic rhinitis.

5.1.2.6 Nasal saline lavage

The role is undefined. A 2007 Cochrane database review noted that nasal saline alone has not been demonstrated to be beneficial in CRS or more effective than an intranasal corticosteroid [26].

Intranasal saline sprays have been found effective in relieving postnasal drip, sneezing, and congestion [27].

5.2 Subgroups of NAR

• Senile rhinitis or rhinitis in elderly: ipratropium bromide is considered effective in reducing the severity and duration of the senile rhinitis (Figure 6) [24, 25, 27].

• Gustatory rhinitis: Ipratropium bromide is effective only for rhinorrhea.

Figure 6.

Therapeutic strategy of nonallergic rhinitis.

It is particular benefit in gustatory rhinitis [25, 27].

• Occupational rhinitis: The treatment is to avoid the trigger [27].

• Hormonal rhinitis: Nasal corticosteroids can be used to improve symptoms [27].

• Drug-induced rhinitis: Treatment is usually focused on cessation of the affecting agent, as well as support with intranasal corticosteroids [25].

• Smokers’ rhinitis: the mainstay of treatment is triggering avoidance [25, 26].

• Idiopathic rhinitis: Intranasal capsaicin (8-methyl-N- vanillyl-6-nonenamide), the active component of chili peppers, appears to have a therapeutic effect in idiopathic rhinitis with long-lasting relief of symptoms from 6 to 9 month in 80% of well-selected IR patients ranging, based on several randomized controlled trials (Figure 6) [24, 25].

5.3 Nonpharmacologic treatment

Surgical interventions are contemplated for patients with allergic rhinitis and non-allergic rhinitis (NAR) who do not respond adequately to medical therapy. A surgical procedure known for its favorable outcomes involves reducing the hypertrophy of the inferior turbinates. This intervention proves to be highly effective for individuals experiencing nasal obstruction that persists despite the clinical treatments described earlier [26].

The surgical techniques for inferior turbinate can be grouped into five groups [28]:

1. Turbinectomy is a procedure that removed turbinate: total, partial or by submucosal resection using cold steel instruments [SMR]

2. Microdebrider-assisted turbinoplasty [MAIT] which was defined by submucosal resection of the inferior turbinate with microdebrider.

3. Radiofrequency ablation [RFA] relying on the use of radio waves to create heat to cause tissue fibrosis and shrinkage.

4. Electrocautery techniques (monopolar/bipolar probe, diathermy electrode, straighttip electrode) which make use of an electrical current to destroy tissue.

5. Laser-assisted turbinoplasty (carbon dioxide, diode, potassium titanyl phosphate) that uses light energy to ablate tissue.

Irrespective of the method employed and the equipment utilized, the primary objectives remain to enhance air passage and minimize complications [29]. The selection of the most suitable technique depends on individual cases, taking into consideration factors such as the anatomy of the inferior turbinate (whether hypertrophy is more associated with bone or mucosa), the extent of hypertrophy (whether it is predominantly anterior or posterior), the availability of equipment, and the proficiency of the surgeon [29].

Another aspect to take into account is the preservation of nasal physiology. The fundamental physiological principles for this approach are [30]:

• The critical zone is the nasal valve region (inferior turbinate head);

• Small area increase = large increase in airflow (exponential correlation between area and airflow);

• Nasal sensation depends in part on the nasal mucosa of the inferior turbinate.

Hence, diminishing the volume of the inferior turbinate could result in a decrease in the quantity and/or activity of the responsive mucosa. This, in turn, could contribute to the amelioration of symptoms such as rhinorrhea, sneezing, and itching, all while maintaining the physiological functions of the mucosal epithelium [31]. Moreover, the alleviation of symptoms may be associated with the disruption of branches of the posterior nasal nerve, key in the mechanisms of sneezing and hypersecretion [31].

In a Systematic Review by Zhang et al. indicates that all techniques described above, significantly improved nasal obstruction post-operatively based on patient-reported outcome measures. No statistical significance was observed when stratifying outcomes by AR and NAR groups, improving is similar for both populations [28], RFA and MAIT improved rhinorrhea significantly compared to baseline [28]. A systematic review by Acevedo et al. assessing outcomes on VAS nasal obstruction found similar results when comparing RFA and MAIT [32], in contrast, Mirza et al. concluded that MAIT resulted better [33].

In relation to alternative techniques, RFA demonstrated comparable enhancements in nasal obstruction compared to electrocautery and turbinectomy/Septoplasty with Mucosal Reduction (SMR) [28]. Improvements in all physiological indicators of nasal patency, encompassing active anterior rhinomanometry (nasal resistance), acoustic rhinometry (nasal cavity volume), and nasal airflow, were observed with RFA, MAIT and laser interventions [28, 32, 33].

RFA and MAIT initially improved, but after 1-year, VAS obstruction scores worsened when compared to 3–6 months postoperatively [28], these results suggest that peak effect following inferior turbinate reduction is achieved within the first year; however patients are still significantly improved relative to baseline; with improvement a favor MAIT at 5 years.

An alternative technique outlined is the endoscopic vidian neurectomy (EVN) and posterior nasal neurectomy (PNN), involving both surgical (SPNN) and cryoablative (CPNN) methods. The systematic review indicates that EVN, SPNN, and CPNN serve as effective and safe surgical options for patients with non-allergic rhinitis (NAR) unresponsive to medical management. Notably, SPNN and CPNN are linked to lower rates of complications, including dry eye and palatal/cheek numbness, in comparison to EVN [34]. Another systematic review reveals that both selective vidian neurectomy (SVN) and PNN result in significantly reduced symptoms in both short-term and long-term postoperative periods when compared to the preoperative phase [35].

Another noteworthy aspect to emphasize pertains to the choice between septoplasty alone or septoplasty combined with turbinoplasty, it is observed that patients undergoing the combined procedure experience more pronounced symptomatic improvement [36].

In summary, the surgical treatment of inferior turbinate hypertrophy should be personalized based on the patient’s clinical condition, with a primary focus on enhancing air space and nasal function [29]. In this context, the importance of experience-based medicine appears to outweigh the reliance on evidence.

6. Conclusions

NAR is a diverse nasal condition characterized by a high global prevalence. Its etiology is related to neurogenic factors. NAR comprises seven subtypes with overlapping presentations. Treatment strategies should prioritize the avoidance of known triggers, and initial therapeutic approaches involve the use of intranasal corticosteroids, intranasal antihistamines and intranasal ipratropium. Combinations of these therapies may be considered if monotherapy fails to adequately manage symptoms. Surgical interventions are contemplated for patients resistant to medical therapy, with effective outcomes noted in procedures such as the reduction of inferior turbinate hypertrophy and selective neurectomy of the vidian branches.