Non-allergic Chronic Rhinosinusitis Research Articles

Interleukin-5 Levels in Chronic Rhinosinusitis Patients With and Without Allergy

<b>Introduction:</b> Chronic rhinosinusitis (CRS) is an inflammation of the nasal mucosa and paranasal sinuses that is present for more than 12 weeks. The pathogenesis of allergic CRS includes mucosal edema and causes sinus ostial obstruction, which. It leads to the infection of the paranasal sinuses. Interleukin- 5 (<i>IL-5</i>) is a cytokine and acts in eosinophil and basophil biology. It is the main effector unit of allergic reactions. </br></br> <b>Aim:</b> This study aimed to determine <i>IL-5</i> levels in allergic and nonallergic chronic rhinosinusitis patients. </br></br> <b>Material and methods:</b> A comparative analytic cross-sectional study was used. A total of 10 allergic chronic and 10 nonallergic chronic rhinosinusitis patients took part in this study. The real-time polymerase chain reaction (RT-PCR) method was used to determine gene expression. Data were analyzed with SPSS. A p-value below 0.05 was considered statistically significant. </br></br> <b>Results:</b> <i>IL-5</i> gene expression in non-allergic chronic rhinosinusitis was higher than in allergic chronic rhinosinusitis. <i>IL-5</i> gene expression was not significant between chronic non-allergic and allergic chronic rhinosinusitis (p > 0.05). There was an elevated <i>IL-5</i> gene expression in non-allergic chronic rhinosinusitis, but it was not significant compared to chronic allergic rhinosinusitis.

Type 2 Inflammatory Shift in Chronic Rhinosinusitis During 2007-2018 in Belgium.

Chronic rhinosinusitis (CRS) is a heterogenic disease with different inflammatory patterns depending on the presence (CRSwNP) or absence (CRSsNP) of polyps and geographical location. A shift toward type 2 endotype has been seen in Asia. We aim to investigate whether there has been type 2 shift in Belgium and to further endotype CRS based on clinical markers. Prospective descriptive study. Four hundred and thirty eight patients with CRS undergoing sinus surgery at Ghent University Hospital between 2007 and 2018 were included and stratified based on phenotype, comorbidities, inflammatory markers in tissue, and two different time points of surgery. Tissue samples from surgery were analyzed for type 2 markers. In a subgroup of CRSwNP blood eosinophils (EBC) was available. There was an increase in type 2 inflammatory markers in the latter group versus the earlier, in non-asthmatic, non-allergic CRS patients regardless of phenotype. The proportion of IL-5+ patients was elevated in the latter group in CRSwNP. Inflammatory markers and comorbidities differ between IL-5+ CRSsNP and CRSwNP subjects, no difference was seen in IL-5- CRS. EBC can together with information on comorbidities help identify type 2 CRSwNP in a clinical setting. There is a shift toward type 2 inflammation within the CRS population over recent 8 years also in Belgium. This shift implies that we expect to see more cases of severe and difficult to treat CRS in the future. Polyp formation is not directly linked to the presence or concentrations of type 2 inflammatory markers. Clinical parameters and EBC > 300 cells/μL can be used to identify type 2 CRSwNP. 3. Laryngoscope, 131:E1408-E1414, 2021.

Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

Arginase Isoform Expression in Chronic Rhinosinusitis.

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

Dynamics of Interleukin-10 Levels in Chronic Rhinosinusitis with/without Allergy

BACKGROUND: Rhinosinusitis occurs when the lining of the nasal and sinuses gets inflamed, infected or irritated, become swollen, and create extra mucus, the swollen lining may also interfere with drainage of mucus. Chronic rhinosinusitis (CRS) is a more persistent problem that requires a specific treatment approach. Aim of this study was to determine changes in interleukin (IL)-10 as an anti-inflammatory cytokines in allergic and non-allergic CRS at Makassar. METHODS: A prospective cohort study was designed to assess the level of IL-10 for three times during two weeks of therapy. Medication of Cefadroxil 500 mg 2x1, Pseudoephedrine 30 mg 2x1, Terfenadine 40 mg 2x1 and Methylprednisolone 4 mg 3x1, was conducted during two weeks for 13 subjects in allergic CRS group and 12 subjects in non-allergic CRS group. Results were statistically analyzed with student t-test and paired t-test.RESULTS: The changes in levels of IL-10 in allergic CRS group were increased, but not significant (5.293 to 5.769, p=0.058), and in non-allergic CRS group were decreased, but not significant (6.125 to 5.475, p=0.103). CONCLUSION: The serum levels of IL-10 were not significant increased in allergic CRS group and not significant decreased in non-allergic CRS group. KEYWORDS: interleukin-10, chronic rhinosinusitis, allergy, cefadroxil, pseudoephedrine, terfenadine, methylprednisolone

Osteitis in chronic rhinosinusitis: a histopathological study of human ethmoid bone remodeling in allergic versus non-allergic chronic rhinosinusitis

Background : Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the mucosa lining the paranasal sinuses; however, recent evidence also indicates the involvement of the sinus bones in the inflammatory process. CRS is a disease with different phenotypes; nonetheless, the characterization of osteitis in the different CRS phenotypes is poorly characterized. Herein, we report on osteitis in two main phenotypes of CRS: a group allergic to aeroallergens who suffers from long-lasting upper airway allergy, and the CRS group with no upper airway allergy. Patients and methodology : A total of 51 patients (23 females and 28 males, with a mean age of 39.03±13.4) who underwent surgery in our university hospital contributed to this study by providing bone samples from the ethmoid bone. They were divided into three groups: group I is patients who underwent septoplasty with or without partial inferior turbinectomy, and they acted as the control group; group II is patients who underwent operation for non-allergic CRS (NACRS); and group III is patients who underwent operation for allergic CRS (ACRS). Sections of the decalcified ethmoid bone were stained with hematoxylin and eosin for histological evaluation for osteitis (periosteal thickening and remodeling, osteoblastic and osteoclastic activity, and osteomyelitis and bone destruction) that was graded from 0 to IV, where grade 0 is normal histology and grade IV is frank osteomyelitis and bone destruction. Results : Descriptive histology of the ethmoid bone analysis demonstrated osteitis of different grades in patients suffering from CRS with or without upper airway allergy. In the ACRS group, 80% demonstrated grade I osteitis, and 20% grade II. However, 11.11% of the NACRS group demonstrated normal bone histology, and 88.88% demonstrated osteitis: 33.33% demonstrated grade I, 50% grade II, and 5.5% grade III. The control group showed normal bone histology in 90.47% and grade I osteitis in 9.52%. The mucosal disease was higher in the grade of inflammation than the osteitis in both CRS groups (II and III). There was no correlation between the mucosal and bone grade of inflammation in both CRS groups. Conclusion : Herein, we show evidence of osteitis in ACRS and confirm the presence of a higher grade osteitis in the NACRS patients. This sinus bone remodeling may contribute to the chronicity of the disease and carries special consideration in the treatment of CRS. Keywords: allergic rhinitis; sinusitis; ethmoid osteitis; periosteal thickening; osteoclasts; osteoblasts (Published: 8 January 2014) Citation: Advances in Cellular and Molecular Otolaryngology 2014, 2 : 23504 - http://dx.doi.org/10.3402/acmo.v2.23504

Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue

Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway.

Improving the Detection of Fungi in Eosinophilic Mucin

To investigate the improvement in histologic detection of fungi with Gomori methenamine silver (GMS) stain by trypsin predigestion in the mucus of patients with chronic rhinosinusitis (CRS). Prospective, single group, descriptive analysis. Multi-institutional. Thirty-four sinus specimens from 12 surgical patients with CRS were stained with hematoxylin and eosin, GMS stain, GMS with trypsin digestion, immunofluorescence stains for chitinase, and anti-Alternaria. All patients received skin testing, total IgE serology, and radioallergosorbent tests (RAST) for 23 fungal-specific IgE antibodies. The conventional GMS stain detected fungi in only 9 of 34 (27%) specimens. Predigesting the specimen with trypsin dramatically improved the visualization of fungi (31/34, 91%). The chitinase immunofluorescence visualized fungi in 32 of 34 (94%), and anti-Alternaria visualized 33 of 34 specimens (97%). Only 8 of 12 (75%) patients had detectable allergies. This report describes a simple modification of the conventional GMS stain that can significantly improve the visualization of fungi on histology and explains the lack of detection in previous studies. These novel, more sensitive histologic methods reveal the presence of fungi within the eosinophilic mucin in allergic and also nonallergic CRS patients, further questioning a crucial role of an IgE-mediated pathophysiology.

Smoking and chronic rhinitis: effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water: A prospective, randomized, double-blind study

PurposeSmoking is a self-destructive behavior that is known to induce remodeling of the lower airways, leading to squamous metaplasia, but little is known about its effects on the nose and paranasal sinuses. Nasal irrigations are often mentioned as measures for treating sinonasal inflammations. The purpose of our study was to compare the effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution in smokers with nonallergic chronic rhinosinusitis, based on clinical and olfactory evidence. Materials and methodsThe present study was a prospective, randomized, double-blind study performed in a tertiary academic referral center. Seventy smokers with nonallergic chronic rhinitis were enrolled. Nasal endoscopy, rhinomanometry, nasal cytology, and odor threshold measurements were performed in subjects randomized to daily nasal irrigations with either thermal water or isotonic sodium chloride solution for 1 month. ResultsImmediately after the treatment, the thermal water irrigations revealed a positive pharmacologic action, judging from a tendency toward lower nasal resistances (P = .07) and larger numbers of ciliated cells in the patients treated (P = .003). Endoscopic findings in the thermal water group were still better than in the control group a further 2 months later (P = .03). ConclusionsOur results indicate that nasal irrigations with thermal water had a good effect on endoscopic objective signs, nasal resistances, and epithelial trophism.

Immunologic response to fungus is not universally associated with chronic rhinosinusitis

In the December 2009 issue of this journal, Orlandi et al presented a study in which peripheral blood mononuclear cells (PBMCs) from chronic rhinosinusitis (CRS) patients (5 from Texas, 5 from Utah) and seven nonhealthy controls were stimulated with fungal extracts. Despite the small numbers, they confirmed important aspects of previous studies: 1) CRS patients' PBMCs react to certain fungal stimuli by producing significantly (P < 0.05) higher amounts of interleukin (IL)-5 and IL-13 when compared to controls; 2) CRS patients have an enhanced humoral response (significantly elevated immunoglobulin [Ig] G levels to Alternaria); and 3) CRS patients react independently from an IgE-mediated allergy, as evidenced by that fact that nonallergic CRS patients also produced IL-5 in response to fungal stimuli. Unfortunately, the authors chose not to highlight their positive results. They emphasized what they failed to demonstrate, specifically an immune response to fungi above a certain threshold in some patients (Utah) with milder CRS. However, these results are potentially explained by the different methods used, and care should be applied when interpreting their results.

Effects of sulfurous, salty, bromic, iodic thermal water nasal irrigations in nonallergic chronic rhinosinusitis: a prospective, randomized, double-blind, clinical, and cytological study

Objectives Nasal irrigations are mentioned among the adjunctive measures for treating several sinonasal conditions. Hyperchromatic supranuclear stria (HSS) in the ciliated cells (CCs) has recently been suggested as a potential cytological marker of the anatomofunctional integrity of nasal mucosa. The aim of this study was to compare the effects of nasal irrigations with sulfurous, salty, bromic, iodic (SSBI) thermal water or isotonic sodium chloride solution (ISCS) in patients with nonallergic chronic rhinosinusitis, considering the endoscopic, functional, microbiological, and cytological evidence (including the ratio of HSS-positive CCs to total CCs [the HSS+ rate]). Methods In a prospective, randomized, double-blind setting, 80 patients were recruited for nasal irrigations with SSBI water or ISCS for 1 month. Results An endoscopically assessed significant clinical improvement was seen after both SSBI thermal water and ISCS irrigations. Before treatment, Staphylococcus aureus was isolated in 5 patients in the SSBI thermal water group and 4 in the ISCS group. After the nasal irrigations, there was no sign of the bacteria in either group. Only the SSBI water irrigations significantly reduced total nasal resistance, as determined by rhinomanometry. Mild nasal irritation (6 cases) and episodes of extremely limited epistaxis (5 cases) were only reported after SSBI thermal water irrigations. Neither type of nasal irrigation significantly increased the mean HSS+ rate at cytological control after 1 month. Conclusions Both types of nasal irrigation improved the endoscopic and microbiological features of patients with nonallergic chronic rhinosinusitis, whereas only SSBI irrigations significantly reduced total nasal resistance. Further investigations are needed based on longer treatments and follow-up periods to establish whether the HSS+ rate is useful for monitoring clinical improvements in chronic rhinosinusitis treated with nasal irrigations.

Mucosal Expression of Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Chronic Rhinosinusitis

Allergic rhinitis (AR) is characterized in part by hyperresponsiveness to nonspecific stimuli, a phenomenon that reflects the fundamental role of nasal neural pathways in chronic airway inflammation. Neurotrophins may serve pivotal roles in mediating hyperresponsiveness in allergic airway disease, although the role of such neurogenic mediators in chronic rhinosinusitis (CRS) is not well understood. This study was designed to examine the expression of two potent neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in CRS. Inferior turbinate and sinus mucosa were obtained from CRS patients with and without nasal polyps (NPs) and from nonallergic controls. Enzyme-linked immunosorbent assay was used for quantitative determination of tissue concentrations of NGF and BDNF. Ninety-four tissue samples from 48 patients were included. Mean concentration of NGF in sinus mucosa was significantly higher in CRS than controls. CRS without NPs was associated with a 60% increase in sinus NGF over controls (p < 0.05), and CRS with NPs was associated with a 140% increase (p < 0.05). Mean sinus NGF concentration was significantly elevated in allergic subjects compared with controls (p < 0.01). A similar trend was noted in subjects with nonallergic CRS, although this did not reach significance. Mean BDNF concentration was decreased in CRS compared with controls, with the most significant decrease in patients with polyps (p < 0.05). Mean turbinate concentration of both NGF and BDNF were similar in controls and CRS. Increased expression of NGF may contribute to neural hyperresponsiveness in CRS sinus mucosa, particularly those patients with NP and/or allergies. BDNF expression is decreased in CRS sinus mucosa. Alterations in neurogenic inflammation may contribute to the pathophysiology of CRS and provide alternative therapeutic targets.

Impact of Allergy on the Prognosis of Functional Endoscopic Sinus Surgery

Purpose Functional endoscopic sinus surgery (FESS) is currently the standard surgical treatment for chronic rhinosinusitis (CRS) refractory to medical therapy. Many studies have reported that patients treated with FESS had excellent objective and subjective outcomes. However, only a few reports have discussed the influence of allergy on the outcome of FESS. The purpose of this study was to understand the impact of allergy on the short-term outcome of FESS. Methods A total of 116 patients with CRS who underwent FESS from June 2000 to February 2003 were enrolled in this study. Patients underwent an intradermal skin test, coronal sinus computed tomography (CT) scan and a questionnaire assessment before FESS was performed. The questionnaire was a 10-item scale developed by the authors to assess rhinosinusitis symptoms. Five items were allergy-related (nasal obstruction, rhinorrhea, sneezing, nasal itching and wheezing) and the remaining five were nonallergy-related (post nasal drip, olfactory disorder, headache or facial pain, ear blockage and cough). All patients in this study received similar medication after operation. Rhinosinusitis symptoms were reevaluated by questionnaires 6 months postoperatively. The questionnaire scores before and after FESS were compared between allergic and non-allergic patients and analyzed by the Mann-Whitney Utest. Results. There were no significant differences in preoperative rhinosinusitis scores between allergic and non-allergic patients. There were no significant differences in the total and nonallergy-related rhinosinusitis scores between the two groups postoperatively. However, the postoperative allergy-related rhinosinusitis scores were significantly higher in allergic patients. conclusions. The short-term outcome of FESS was similar in allergic and non-allergic CRS patients when allergic patients received adequate pharmacotherapy to control allergy symptoms.

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Neutral endopeptidase activity and concentration of sensory neuropeptide in the human nasal mucosa.

Human nasal mucosa biopsy samples were studied by biochemical and histological methods to determine whether the concentration of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) as a marker of sensory nerves was dependent on the activity of neutral endopeptidase-like enzyme (NEP-LE). Mucosal samples from the middle turbinate were obtained from 32 patients undergoing functional endoscopic nasal surgery for non-allergic chronic rhinosinusitis. The degree of symptoms related to nasal obstruction, rhinorrhea and headaches was recorded. The number of inflammatory cells in each biopsy sample was evaluated by conventional histopathological examination. CGRP-LI was measured by radioimmunoassay. The activity of NEP-LE was evaluated in vitro using [3H] Leu5-enkephalin as substrate. A good correlation was observed between increased concentrations of CGRP, abundant inflammatory cells and the intensity of symptoms (R2 = 0.80). A low activity of NEP-LE was associated with a high concentration of both inflammatory cells and CGRP, suggesting that NEP-LE activity was reduced during inflammation. These observations further support the hypothesis that reduced degradation of sensory neuropeptides could be involved in the pathophysiological mechanisms of non-specific chronic rhinosinusitis.