Eosinophils and mast cells: a comparison of nasal mucosa histology and cytology to markers in nasal discharge in patients with chronic sino-nasal diseases

Allergic rhinitis (AR), nasal polyps (NP) as well as chronic rhinosinusitis (CRS) are all known to be associated with eosinophilic infiltration and elevated numbers of mast cells (MC) within the mucosa. Both cell types and their markers eosinophilic cationic protein (ECP) and tryptase are utilized in the diagnosis and management of chronic sino-nasal diseases. Mucosal cytology samples were gathered by cytobrush, histological samples were obtained from the inferior turbinate. In both sample sets, the number of eosinophils and MC was determined. Their corresponding markers ECP and tryptase were quantified from nasal discharge. Patients were grouped with reference to their main diagnosis: AR (n = 34), NP (n = 25), CRS (n = 27) and controls (n = 34). Eosinophil counts from cytobrush and ECP levels were significantly elevated in NP compared to all other groups—31- and 13-fold over control, respectively. However, histologic review did not reveal any difference in eosinophil count among groups. Tryptase was significantly elevated threefold in AR versus CRS and controls. No correlation to cytological and histological MC counts could be found. ECP levels in nasal discharge as well as eosinophil counts can provide useful information with regard to the diagnosis. Likewise, tryptase concentrations can do. The presented data show that the measurement of markers in nasal discharge is superior in differentiating among diagnosis groups. Given that the collection of nasal secretions is more comfortable for patients than the more invasive techniques, we recommend first line ECP and tryptase testing performed on nasal secretions.     

Effects of topical nasal steroids and diclofenac on the nasal mucosa during hyperbaric oxygen therapy: a double-blind experimental study

We aimed to evaluate nasal mucosal changes and efficiency of nasal steroids and diclofenac on nasal mucosa during hyperbaric oxygen (HBO) treatment. Forty adult Albino–Wistar rats were randomized into four groups. Group 1 (control group) (n = 10) not exposed to hyperbaric or enhanced oxygen concentrations; group 2 (HBO group) (n = 10) underwent only HBO treatment; group 3 (n = 10) received HBO and intranasal mometasone furoate (10 μl/day); group 4 (n = 10) treated with HBO and diclofenac sodium (10 mg/kg/day ip). Specimens of nasal mucosa were collected after sacrificing and dissection of animals. The specimens were processed for light microscopic evaluation, and then evaluated histopathologically for fibroblastic proliferation and inflammation. Regarding the scores of inflammation, the level of inflammation in the control group was significantly less severe than the other groups (p < 0.05). Evaluation of the fibrosis scores showed that the scores of both groups 2 and 4 were significantly increased (p < 0.05). There were no statistically significant differences between groups 2, 3, and 4 as for fibrosis and inflammation (p > 0.05). Chronic HBO treatment induced mild inflammation of the nasal mucosa. These effects cannot be prevented adequately by administration of nasal steroids and diclofenac.     

Identification of nasal bacterial flora profile and carriage rates of methicillin-resistant Staphylococcus aureus in patients with allergic rhinitis

The aim of the present study was to evaluate the effect of allergic rhinitis (AR) on the nasal flora and colonization rates of resistant microorganisms in comparison to healthy individuals. This colonization may be important in terms of AR-related disorders, the resistant microorganisms’ carriage, and its complications and co-morbidities. The study was performed with two groups. The study group was composed of 54 adult patients with AR. The control group was composed of 50 healthy individuals. None of the individuals in both groups have used any antibiotics, local or systemic steroid within the last month. Composition of bacterial nasal flora and carriage rates of methicillin-resistant Staphylococcus aureus (MRSA) were evaluated with conventional methods by taking nasal smears with a swab. In the study group, methicillin-sensitive coagulase-negative staphylococci (MRCNS) were detected in 30 %; whereas diphtheroids in 25 %, methicillin-resistant coagulase-negative staphylococci in 13 %, methicillin-sensitive S. aureus in 9 %, methicillin-resistant S. aureus in 3.7 %, and extended-spectrum beta lactamases-positive gram-negative bacilli (GR-ESBL+) in 3.7 % were detected. In the control group, methicillin-sensitive coagulase-negative staphylococci were detected in 54 %; whereas diphtheroids in 21 %, methicillin-resistant coagulase-negative staphylococci in 1.5 %, methicillin-sensitive S. aureus in 16 %, methicillin-resistant S. aureus in 1.5 %, Gr-ESBL(?) in 4 %, and viridians streptococci in 3 % were detected. It is found that the MRSA and MRCNS colonization is higher in patients with AR. This colonization may be important in terms of AR-related disorders, the resistant microorganisms’ carriage, and its complications and co-morbidities in comparison to healthy subjects.     

Simultaneous in vivo measurements of intranasal air and mucosal temperature

Nasal cavity volume and blood temperature along the nasal airways, reflecting the mucosal temperature, are considered to be the most important predictors of nasal air conditioning. The purpose of this study was to simultaneously in vivo measure intranasal air as well as mucosal temperature for the first time. Fifteen healthy subjects were enrolled into the study. Two combined miniaturized thermocouples were used for simultaneous recording of intranasal air and mucosal temperature within the anterior turbinate area close to the head of the middle turbinate without interruption of nasal breathing. The highest air and mucosal temperature values were detected at the end of expiration, the lowest values at the end of inspiration. The difference was statistically significant (P < 0.05). The mean mucosal temperature ranged from 30.2 ± 0.9 to 32.2 ± 0.8°C. The mean air temperature ranged from 28.5 ± 1.2 to 34.1 ± 0.7°C. The mean differences between air and mucosal temperature were 1.7 ± 0.5°C after inspiration and 1.9 ± 0.7°C after expiration. Simultaneous measurements of intranasal air and mucosal temperature are practicable. The detected temperature gradient between air and mucosa confirm a relevant heat exchange during inspiration and expiration. This gradient between air and mucosa is obligatory for heat and water exchange to ensure adequate nasal air conditioning.     

Expression of the cysteinyl leukotriene 1 receptor and glucocorticoid receptor-β in nasal polyps

The objective of this study was to analyze the expression of cysteinyl leukotriene 1 (CysLT1) receptor and glucocorticoid receptors (GRs) in nasal polyps, and to evaluate the relationship between the expression of CysLT1 receptors and that of GRs. Nasal polyps were taken from 32 patients of chronic rhinosinusitis with nasal polyposis. Samples of middle turbinate from seven healthy subjects were used as controls. Specimens were immunohistochemically stained for CysLT1 receptor, GR-α and GR-β receptor, and were quantified in the unit area of the tissues. Numbers of CysLT1 receptor-positive cells were much increased in nasal polyps than in middle turbinate (281 ± 67 vs. 157 ± 85 cells/mm², P = .01). There was no significant difference in the numbers of GR-α positive cells between nasal polyps and normal turbinate mucosa. GR-β positive cells were increased in nasal polyps as compared to normal turbinate mucosa (36 ± 8 vs. 19 ± 7 cells/mm², P = .03). A significant relationship was found between the expression of CysLT1 receptor and GR-β in nasal polyps (R = .525, P = .04), whereas there was no significant relationship between the expression of CysLT1 receptor and GR-α in nasal polyps. Our study shows that CysLT1 receptor expression predominates on GR-β over-expressed polyps. This may suggest the additional effect of CysLT1 receptor antagonist for the treatment of nasal polyposis resistant to steroid alone.     

Nasal and middle ear ciliary beat frequency in chronic suppurative otitis media

The middle ear mucociliary system has been shown to have an important function in the clearance of effusions. Little is known, however, about its role in chronic suppurative otitis media (CSOM). The ciliary beat frequencies of middle ear mucosal biopsies and nasal brushings of 27 patients with CSOM were analysed using a computerized photometric technique. The ciliary beat frequency in the middle ear mucosa was significantly less than that in nasal mucosa. Frequency in ears of smoking patients was significantly lower compared with non-smoking patients. Nasal brushings were taken from 27 otherwise healthy age and sex-matched non-smoking controls and the ciliary beat frequency was very similar to nasal samples from patients with CSOM. Ear controls were obtained from otosclerotic patients undergoing tympanotomy and the beat frequency was significantly higher than in the ear of patients with CSOM. It is concluded that middle ear ciliary function is significantly reduced in CSOM, particularly in patients who smoke.     

Acoustic rhinometry in the evaluation of nasal obstruction

Acoustic rhinometry (AR) is a recently developed objective technique for assessment of geometry of the nasal cavity. The technique is based on the analysis of sound waves reflected from the nasal cavities. It measures cross-sectional areas and nasal volume (NV). To obtain dependable assessments of nasal resistance by rhinomanometry or cross-sectional area measurements by AR, it is essential that the structural relations of the compliant vestibular region remain undisturbed by the measuring apparatus. The use of nozzles in making these measurements carries a great risk of direct distortion of the nasal valve. We used a nasal adapter that does not invade the nasal cavity and a chin support that stabilizes the head. In 51 healthy nasal cavities, the average minimum cross-sectional area (MCA) was 0.62 cm² at 2.35 cm from the nostril and 0.67 cm² at 2 cm from the nostril, respectively, before and after topical decongestion of the nasal mucosa. The MCA and NV findings in this group were significantly higher than MCA and NV (P<0.001) in people with structural or mucosal abnormalities before mucosal decongestion. After mucosal decongestion, the MCA and NV were significantly higher in healthy nasal cavities than in nasal cavities with structural abnormalities (P<0.001) but were not higher than nasal cavities with mucosal abnormalities (MCA, P = 0.05; NV, P = 0.06). A nozzle was applied in 20 healthy nasal cavities after mucosal decongestion, and a significantly higher MCA was found compared to measurements made with the nasal adapter (P = 0.02). We conclude that the nasal adapter, which does not invade the nasal cavities, avoids the distortion of the nasal valve and gives more accurate results.     

Pathomorphologische Veränderungen bei der allergischen und idiopathischen Rhinitis

Background

Nasal hyperreactivity is one of the most important underlying mechanisms in allergic rhinitis (AR) as well as idiopathic rhinitis (IR). The aim of the present study was to examine pathomorphological changes in nasal mucosa in these subgroups of rhinitis.

Patients and methods

Tissue samples of human inferior turbinates from 20 patients with AR and 16 patients with IR were taken during nasal surgery and preserved in glutaraldehyde or paraformaldehyde. Ultrathin sections of specimens from 15 patients without chronic inflammation of nasal mucosa were used as controls. Primary antibodies against substance P (SP), calcitonin-gene-related peptide (CGRP), and endothelial nitric oxide synthase (NOS III) were applied, and the immunocomplexes were visualized by an immunocytochemical staining technique using gold-labeled antibodies. Immunostained structures were photodocumented using light and transmission electron microscopy.

Results

The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. A strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation. Extensive edema and cellular infiltrations were found in AR. A decreased presence of eosinophils and nitric oxide was observed in IR.

Conclusions

On the ultrastructural level, AR and IR showed many similarities but also some differences. Based on these findings, anti-inflammatory therapy could be recommended for both types of rhinitis.     

Staphylococcal enterotoxin B induced expression of IL-17A in nasal epithelial cells and its association with pathogenesis of nasal polyposis

Interleukin (IL)-17A is a highly inflammatory cytokine and is known to be produced by Th17 cells. The importance of IL-17A expression in nasal epithelial cells is not well understood. The goal of this study is to explore the expression of IL-17A in nasal epithelial cells in vivo and in vitro. IL-17A and staphylococcal enterotoxin B (SEB) were detected by immunofluorescence (IF) in nasal epithelial cells of control mucosa (n = 10) and nasal polyps (n = 20). Expression of IL-17A, RORC, IL-6, and TGF-β1 was also measured by RT-PCR in the tissue of control nasal mucosa (n = 10) and nasal polyps (n = 20). IL-17A expression was evaluated in the human nasal epithelial cells after SEB stimulation. Finally, IL-17A expression was demonstrated by immunohistochemistry and IF following intranasal SEB instillation in mice. Expression of IL-17A in nasal epithelial cells was higher in nasal polyps compared to control mucosa. There was a significant correlation between IL-17A and SEB detection in nasal polyps using IF. SEB increased IL-17A expression in human nasal epithelial cells, and in epithelial cells of SEB instilled mice. In conclusion, SEB exposure of nasal epithelial cells induces the enhanced expression of IL-17A. SEB may be involved in pathogenesis of nasal polyps by enhancing IL-17A expression in epithelial cells in nasal polyps.     

The obstructive nasal septum. Effect of simulated deviations on nasal airflow resistance

Effects of simulated septal deviations on nasal airflow resistances were assessed by rhinomanometry in healthy human adults. Obstructions 5 x 15 mm protruding 1 to 5 mm into the nasal lumen were applied to the septum in untreated and decongested nasal cavities. The most resistive septal site was located opposite the caudal edge of the upper lateral cartilage where a 3-mm deviation increased resistance substantially in untreated noses, but produced no resistive effect when the mucosa was decongested, whereas a 4-mm deviation increased resistance severely at this site in untreated and decongested noses. Deviations at the caudal end of the septum that overlapped the upper lateral cartilage were markedly resistive also, while near the cavum they were less resistive. Decongestion reduced resistance and length of this anterior-resistive nasal segment. By contrast, within the cavum neither deviations of 5 mm nor mucosal status affected resistance. It is concluded that airflow resistance of the nasal cavum is unresponsive to septal deviations and mucosal status, but the anterior part of the nose is most susceptible and differences of 1 mm in lumen can be critical.     

Nasal mucosa reaction. A model for mucosal reaction during challenge.

Rhinological symptoms in aspects of hyperreactivity and allergy are increasing problems. Previous reports on this subject are based on studies of airway obstruction (rhinomanometry), secreted substances during challenge, and symptom scores. To be able to define and evaluate the pathological reactions in nasal hyperreactivity and allergy, it is necessary to find principles to describe and standardize the reactions of the healthy nasal mucosa. The aim of this study was to examine congestion of the nasal mucosa in healthy volunteers. Existing measuring methods, in this aspect, are either indirect or not accurate enough for this purpose. With the development of rhinostereometry, an optical measuring method, it is possible to record nasal mucosa congestion with high accuracy. A nasal challenge test was made in healthy volunteers with gradually raised concentrations of a histamine solution, which was applied to the inferior concha on the right side. Recordings of the mucosal congestion were made with rhinostereometry. We found that it is possible, with statistical significance, to standardize the reactions of the healthy nasal mucosa: There is no congestion more than 0.4 mm with a histamine concentration of less than 4 mg/ml (p less than 0.05); congestion of more than 0.4 mm is present at histamine concentrations of 16 mg/ml (p less than 0.05).     

Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo

OBJECTIVE: Benzalkonium chloride (BC) is a preservative commonly used in nasal decongestant sprays. It has been suggested that BC may be harmful to the nasal mucosa. The present study, involving healthy volunteers, examines effects of BC on nasal mucosal end-organ functions. METHODS: Isotonic saline and BC (0.1 mg/mL) were administered acutely to the nasal mucosa using a nasal pool device. Nasal symptoms were determined. Nasal lavage fluid levels of alpha2-macroglobulin and fucose were measured as indices of plasma exudation and glandular secretion, respectively. In addition, BC (0.1 mg/mL) was given as single actuations of 100 microL per nasal cavity three times daily for 10 days. The ability of histamine (0.4 mg/mL) to evoke nasal symptoms and plasma exudation responses was determined before and after the repeated BC administration series. RESULTS: BC produced immediate nasal smart or pain (P < .05), but tolerance to this response developed by repeated administrations. BC increased nasal mucosal output of fucose (P < .05), whereas nasal lavage fluid levels of alpha2-macroglobulin were unaffected. Histamine produced significant symptoms and mucosal exudation of alpha2-macroglobulin (P values < .01), equally before and after the 10 days of BC exposure. CONCLUSIONS: BC in dosages commonly used as preservative in nasal decongestant sprays produced short-term glandular secretion and nasal smart or pain. However, 10 days' frequent exposure to BC was not associated with untoward symptomatic effects, nor was a sensitive mucosal variable such as histamine-induced exudative responsiveness affected by this repeated exposure 1 BC.     

P物质在变应性鼻炎中对RANTES mRNA表达的影响及其意义

目的：探讨P物质（SP）在变应性鼻炎（AR）中对RANTESmRNA表达的影响及其意义,深入了解AR的发病机制。方法：以卵清蛋白（OVA）建立AR豚鼠模型（模型组）。然后用SP滴鼻激发AR各组,并与正常豚鼠对照（对照组）,观察其症状和鼻黏膜病理学变化,并对鼻腔灌洗液中的嗜酸粒细胞进行计数。采用RT—PCR方法,对各组动物鼻黏膜组织中RANTES mRNA的表达水平进行相对定量比较。结果：SP激发能诱发正常的豚鼠出现相似的AR症状,并能加重模型组豚鼠AR症状和鼻黏膜炎症。而且SP滴鼻使AR豚鼠鼻黏膜RANTES mRNA的表达显著增高（P〈0．05）,鼻灌洗液中嗜酸粒细胞数亦明显增高（P〈0．01）。结论：在AR的发病机制中,SP能诱导鼻黏膜表达RANTES,促进嗜酸粒细胞趋化与转运,引发和加重AR的炎症反应。     

Simulated septal deviations

Effects of simulated septal deviations on nasal airflow resistance were measured in two healthy young adults by computer-assisted rhinomanometry. Within the decongested bony cavum, simulated deviations, 30 x 5 x 5 mm perpendicular to the maxillary crest, elevated resistance only slightly, but severely when the mucosa was not decongested. Caval resistance was unaffected by simulated maxillary crest spurs, 30 x 5 x 5 mm, in either vascular state. Between inferior turbinate and anterior naris, 5-mm septal protrusions from floor to roof increased resistance severely, but when shortened by one third, their resistive effects were markedly decreased, especially when positioned near the roof. The cavum can accommodate large septal spurs, deviations, and congested mucosa with little effect on airflow resistance. By contrast, resistance of the anterior nasal airway beyond the inferior turbinate bone is acutely responsive to changes in mucosal congestion and to septal protrusions, especially when they are situated near the floor of the nose.     

A computed tomographic study of nasal mucosa: effects of vasoactive substances

Computed tomographic studies of mucosal responses to vasoactive substances (xylometazoline and histamine) in healthy nasal cavities of adult subjects demonstrate the distribution of erectile mucosa. Following artificial congestion of the mucosa by local application of histamine: (1) the middle turbinate and the body of the inferior turbinate limit the main nasal airway as it passes through the middle meatus; (2) an expanded mass of localized erectile tissue in the anterior septal region bars the entrance to middle meatus and intrudes medially into the narrow airway of the piriform aperture and nasal valve; (3) this critical segment of the airway is further limited by forward extension of the anterior tip of the inferior turbinate.     

Thresholds in nasal histamine challenge in patients with allergic rhinitis, patients with hyperreflectory rhinopathy, and healthy volunteers

BACKGROUND: Characteristic symptoms of hyperreflectory rhinopathy include recurrent sneezing, nasal obstruction, and nasal secretion without an allergic background. The diagnosis can only be made if all differential diagnoses have been excluded. So far no clinical test has been established to reliably diagnose hyperreactivity of the nasal mucosa. The present study aimed to investigate whether nasal provocation with histamine allows identification of patients with hyperreflectory rhinopathy. MATERIALS AND METHODS: One-sided nasal challenge with histamine was applied to 13 patients with allergic rhinitis, 13 patients with hyperreflectory rhinitis, and 12 healthy volunteers. Histamine concentrations used were 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL. Test results were quantified using a symptom score (positive at values above 3) and active anterior rhinomanometry (positive at a reduction of airflow of 40% or more in comparison to challenge with solvent). RESULTS: While there was a significant difference between controls and patients with allergic rhinitis or hyperreflectory rhinopathy, respectively, no significant difference was observed between the two groups of patients. Results indicated that one-sided nasal provocation with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. In terms of the differentiation between subjects with hyperreactivity of the nasal mucosa and healthy controls, the sensitivity of one-sided nasal histamine provocation with 1 mg/mL was found to be 100%; its specificity was 83% if it was evaluated by rhinomanometry and symptom score. CONCLUSION: The present results indicate that one-sided nasal challenge with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. However, the test does not differentiate between patients with allergic rhinitis and patients with hyperreflectory rhinitis.     

变应性鼻炎动物模型血一氧化氮和鼻黏膜一氧化氮合酶的动态检测

目的探讨在变应性鼻炎（allergic rhinitis,AR）发病及应用抗过敏药物治疗过程的不同阶段,变应性鼻炎动物模型血一氧化氮（Nitric Oxide,NO）水平和鼻黏膜一氧化氮合酶（Nitric-Oxide Synthase,NOS）表达的动态变化。方法选用健康SD大鼠50只,将其随机分为5组：正常指标组、实验1组、实验2组、实验3组、治疗组。在不同阶段分别取血和鼻黏膜;检测血浆中NO含量及鼻黏膜匀浆液NOS含量。结果实验1组和实验3组动物的血浆NO及鼻黏膜匀浆上清液NOS含量均显著升高,实验2组的NO及NOS含量均无显著变化;治疗组NO含量降至正常指标组水平,NOS亦有部分下降。血浆NO与鼻黏膜NOS含量之间存在显著的正相关关系（r=0．770,P=0．013）。结论血浆NO及鼻黏膜NOS水平在AR造模的不同阶段有明显的波动性变化,常规抗过敏药物能有效抑制患病机体NO的产生。血NO含量的变化能较好地反应鼻黏膜NOS活性的改变。     

射频消融术治疗慢性肥厚性鼻炎

目的：探讨射频消融治疗慢性肥厚性鼻炎所致鼻塞的效果及对鼻黏膜功能的影响。方法：采用射频消融术治疗慢性肥厚性鼻炎60例的双侧下鼻甲，术前及术后3个月应用视觉模拟评分表（visual analogue scale, VAS）评价鼻塞的主观感觉；应用糖精试验法测定术前及术后3个月的鼻腔黏膜纤毛输送率（mucociliary transport rate, MTR）。结果：术前鼻塞VAS评分左侧为（68.7±9.6）%，右侧为（72.5±10.2）%；术后3个月左侧为（35.0±9.0）%，右侧为（40.3±10.6）%，与术前相比，差异均有统计学意义（P＜0.01）。随访3个月，双侧下鼻甲与鼻中隔的最小距离从术前小于0.2?cm增加到术后大于0.3?cm。术前鼻黏膜纤毛MTR为（7.64±1.56）mm/min，术后3个月鼻黏膜纤毛MTR为（6.89±2.01）mm/min，与术前比较差异无统计学意义（P＞0.05）。结论：射频消融术是治疗慢性肥厚性鼻炎所致鼻塞的较好方法，对鼻黏膜纤毛无明显影响，未破坏鼻黏膜纤毛的正常生理功能     

Acoustic rhinometry in persons recruited from the general population and diagnosed with chronic rhinosinusitis according to EPOS

Chronic rhinosinusitis (CRS) is a disease related to the nose and the paranasal sinus as defined by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. The criteria include subjective symptoms, such as nasal obstruction, and objective findings by endoscopy. Acoustic rhinometry (AR) is an objective method to determine nasal cavity geometry. The technique is based on a sound pulse reflection analysis in the nasal cavity and determines cross-sectional areas as a function of distance as well as volume. AR measurements in persons recruited from the general population, with and without CRS based on the clinical EPOS criteria, were investigated. As part of a trans-European study, 362 persons, comprising 91 persons with CRS and 271 persons without CRS, were examined by an otolaryngologist including rhinoscopy. Minimum cross-sectional area, distance to minimum cross-sectional area, and volume in the nasal cavity were measured by acoustic rhinometry and all participants underwent Peak Nasal Inspiratory Flow (PNIF) and allergy test. A difference in AR was found before and after decongestion, but no difference was seen between CRS patients and controls. Positive correlation between AR and PNIF was found and AR was capable of identifying mucosal oedema and septum deviation visualised by rhinoscopy. In conclusion, AR, as a single instrument, was not capable of discriminating persons with CRS from persons without CRS in the general population. However, AR correlates well with PNIF and was capable of identifying septum deviation and mucosal oedema.