Inferior turbinate goblet cell secretion in patients with perennial allergic and nonallergic rhinitis

Perennial rhinitis is clinically associated with a significant increase in nasal mucus secretion. Moreover, it has already been established that the number of goblet cells, in the inferior turbinates of patients with perennial allergic and nonallergic rhinitis, does not differ from that of normal subjects. Thus a question is raised, whether the above-mentioned phenomenon is ascribed exclusively to submucosal glandular activity, or may also be a result of a nonhyperplastic increase of goblet cell functional activity. This study was conducted to assess inferior turbinate goblet cell mucus secretion in a cohort of patients with perennial allergic and nonallergic rhinitis compared with normal controls. A semiquantitative morphometric method was used to examine goblet cell mucus secretion in sections stained with Alcian blue and periodic acid Schiff. Mucus secretion in each section was established in terms of secretory ratio, calculated as the number of secreting goblet cells divided by the number of nonsecreting ones. The mean secretory ratio of patients with perennial allergic (n = 11) and nonallergic rhinitis (n = 23) was 0.89 and 0.57, respectively, compared to controls (n = 10) 0.25. Statistical analysis confirmed that the secretory ratio of patients with perennial allergic rhinitis was significantly higher than that of the control group. No significant difference prevailed between patients with perennial nonallergic rhinitis and controls, as well as between allergic and nonallergic patients. Based on the results of the study, a basal state of nasal goblet cell mucus secretion in nonstimulated healthy people was established. Furthermore, it was concluded that the enhancement in mucus discharge, from the inferior turbinate goblet cells of patients with perennial allergic rhinitis, was attributed to a nonhyperplastic increase of nasal goblet cell functional activity.     

Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in the nasal mucosa of patients with rhinitis

Since nitric oxide (NO) can be involved in multiple physiological and pathological functions, we evaluated its possible involvement and that of peroxynitrite in the pathogenesis of rhinitis. Inferior nasal turbinates were obtained from allergic rhinitis and nonallergic rhinitis patients during corrective nasal surgery. The expressions of the inducible form of nitric oxide synthase (iNOS) and the production of peroxynitrite and its metabolite 3-nitrotyrosine were examined by immunohistochemistry in consecutive tissue sections. Each section (or tissue compartment) was given a score of 0–4 according to the labeling intensity seen, with the highest number representing the highest labeling intensity. The results showed that iNOS expression was present mainly in the mucosal epithelium, vascular endothelium, and submucosal glands. A significant difference was only observed in the labeling scores of glandular tissues of the allergic group, which had a higher iNOS labeling score. We also found that sections with a higher iNOS level did not necessarily exhibit a higher 3-nitrotyrosine labeling intensity. These data suggest that iNOS-derived NO may have a role in the pathophysiology of rhinitis, especially the glandular function of allergic nasal mucosa. Moreover, our findings suggest that the production of peroxynitrite in rhinitis patients is not dependent on the level of iNOS alone. Received: 23 September 1999 / Accepted: 4 November 1999     

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.     

Nasal hyperreactivity to methacholine measured by acoustic rhinometry in asymptomatic allergic and perennial nonallergic rhinitis

This study was carried out to assess nasal response to different doses of methacholine and to evaluate the diagnostic possibilities of this test. Thirty-seven patients with allergic rhinitis induced by pollen (out of season), 16 with nonallergic rhinitis, and 25 normal subjects were evaluated. After provocation with saline, increasing doses of methacholine, ranging from 0.5 to 16 mg/mL, were applied. Nasal obstruction was assessed by acoustic rhinometry 10 minutes after each dose, the minimum cross-sectional area and the nasal volume in both fossae were obtained. Ipratropium bromide was applied after the last dose of methacholine to evaluate reversibility. After methacholine challenge with 0.5, 1, 2, and 4 mg/mL there was a statistically significant decrease (p < 0.05) in nasal area and volume in a dose-dependent manner in patients with allergic and nonallergic rhinitis in comparison with controls. A ROC (receiver-operating characteristic) analysis showed that a decrease in nasal volume > or = 20% at methacholine concentration of 2 mg/mL is able to predict the presence of rhinitis (positive predicted value 93%, negative predicted value 79%) in 75% of subjects. The clinical relevance of this finding suggests that patients with symptomatic nonallergic rhinitis or even asymptomatic patients with allergic rhinitis out of pollen season present a nasal hyperreactivity to methacholine, and that a decrease of nasal volume > 20% by acoustic rhinometry after challenge with methacholine at 2 mg/mL is able to discriminate these patients from normal subjects. This method seems to be a suitable tool in the diagnosis of rhinitis.     

Localisation of heme oxygenase isoforms in allergic human nasal mucosa

Carbon monoxide (CO) is an endogenously produced gas mediator produced by heme oxygenase (HO). Like nitric oxide (NO), CO is produced in the nasal mucosa. Given that induced NO synthase (iNOS) expression in nasal mucosa has been found to be up-regulated in allergic rhinitis, the current study investigated the expression of HO isoforms in allergic human nasal mucosa. Immunohistochemical staining for type 1 and 2 HO isoforms were carried out in nasal inferior turbinate mucosa from six patients with persistent allergic rhinitis, and compared with six control patients without nasal allergy. Focal and weak expression of HO-1 was observed in seromucous glands, with no difference between allergic and control specimens. Vascular endothelium, erythrocytes, smooth muscle and inflammatory cells (except macrophages) in the allergic group exhibited stronger HO-1 immunoreactivity compared to the control. Minimal expression was found in the respiratory epithelium in either group. Intravascular HO-1 expression was found in the allergic mucosa only. Intense HO-2 immunoreactivity was observed in the respiratory epithelium, vascular endothelium and seromucous glands in both allergic and control groups with no differences in intensity. In conclusion, unlike iNOS, HO-1 is minimally expressed in the nasal respiratory epithelium of either group. However, our findings suggest that it may be involved in the inflammatory process of allergic rhinitis at the submucosal level.     

Reduced TLR2 gene expression is a feature of chronic rhinitic mucosa supporting the hygiene hypothesis

Objective. Pathogenic induction of the immunomodulators toll like receptors (TLRs) and beta‐defensins (HBD) can steer the developing immune system toward a Th1 nonallergic pathway and might explain why farmer's children show reduced frequency of allergy. We hypothesised that chronic allergic and nonallergic rhinitis might be associated with reduced mucosal levels of TLRs and HBDs. Method. The gene expression levels of TLR2 & 4 and HBD1‐4 was determined by real‐time polymerase chain reaction in sections of nasal turbinate tissue from adults with persistent allergic and idiopathic rhinitis, healthy nasal mucosa and tonsil tissue. Immunohistochemistry was used to study the localisation and distribution of proteins for TLR2, HBD2, α‐defensins (1‐3) and neutrophil elastase Results. A significant reduction in TLR2 mRNA expression was identified in allergic mucosa compared to control mucosa, with generally reduced expression for TLR4 and HBDs. While not significant, the nonallergic group also showed reduced expression for TLRs and HBDs. With the exception of HBD4, increased gene levels were seen in tonsil tissue. HBD2 and TLR2 protein expression was localised in lining and submucosal glandular epithelium but insignificant differences were seen for HBDs, TLRs, neutrophils and α‐defensin between the rhinitic and control patient groups. Conclusion. Chronic rhinitic mucosa shows reduced levels of TLR and HBD gene expression. The significant reduction in TLR2 gene expression in adult allergics support the concept that increased TLR2 is protective against the development of allergy.     

The relationship between allergy and rhinosinusitis

BACKGROUND: IgE-mediated hypersensitivity is considered by some to be a predisposing factor for developing rhinosinusitis, although the theory is still controversial. The purpose of this study was to evaluate the relationship between allergy and rhinosinusitis. DESIGN: A cross-sectional study. METHODS: 198 rhinitis patients were enrolled. An allergy skin prick test was done and the subjects categorized as allergic or nonallergic. Nasal endoscopy and sinus radiography were performed. The criteria for diagnosis of rhinosinusitis were rhinitis symptoms and positive nasal endoscopy (discharge from middle and/or superior meatus) and/or abnormal sinus radiography. RESULTS: Allergic patients were significantly more likely to have abnormal findings on sinus radiography than non-allergic patients (p < 0.001) and would therefore fulfill the criteria on which rhinosinusitis may be diagnosed, but the two groups were not significantly different in positive nasal endoscopy results (p = 0.553). Among the patients with abnormal sinus radiography, the allergic patients were significantly less likely to have a positive nasal endoscopy compared to the nonallergic patients (p = 0.006). CONCLUSIONS: Allergic rhinitis subjects were significantly more likely to have abnormal findings on sinus radiography compared with nonallergic subjects potentially leading to a diagnosis of rhinosinusitis. However, they were also significantly more likely to have abnormal sinus radiography with negative nasal endoscopy than the nonallergic subject. These findings could suggest an association between allergic rhinitis and rhinosinusitis via IgE mediated hypersensitivity.     

Immunoelectron microscopic findings in patients with allergic rhinitis

BACKGROUND: In middle Europe the prevalence of allergic rhinitis is up to 15 % to 25 %. Allergic rhinitis is characterised by an inflammation of the nasal mucosa induced by different allergens. The patients suffer from symptoms like sneezing, rhinorrhea and nasal airway obstruction caused by morphological changes of the nasal mucosa. This symptomatology is considered to be a result of accumulation and activation of inflammatory cells. Further some neuropeptides like Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) play an additional role in pathophysiology of allergic rhinitis. PATIENTS AND METHODS: Tissue samples from 28 human turbinates of patients with perennial rhinitis were taken during nasal surgery and preserved in phosphate-buffered glutaraldehyde or paraformaldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. After polymerization an immunocytochemical staining-technique using a gold-labeled antibody was carried out. Immunostained structures were photodocumented by using a transmission electron microscope. RESULTS: In the lamina propria mucosae an extensive edema and several inflammatory cells like lymphocytes, plasma cells, eosinophiles and macrophages was found. The capillaries showed an activated endothelium. Immunoreactive nerve fibers were found in the periglandular tissue around the acini, ducts and in the glandular connective tissue. Neuroglandular synapses with dense core vesicles and positive immunoreactions to CGRP and SP could be detected. Neuropeptidergic axons were often observed near to plasma cells. CONCLUSIONS: In the edematous nasal mucosa an infiltration with different inflammatory cells was found. Using electron microscopical techniques nerve structures near the submucosal glands could be demonstrated. Immunoreactions to the neuropeptides CGRP and SP were detected in the periglandular nerves and in neuroglandular synapses. These findings demonstrate the direct nerve control of glandular functions in allergic rhinitis. CGRP is generally known to have a vasodilatatory effect and to stimulate the secretion of nasal seromucous glands. In addition, SP as a short-acting vasodilatator may induce vascular permeability and glandular secretion. These immunoelectron microscopical findings further elucidate pathomorphological mechanisms in allergic rhinitis.     

Glycoconjugate expression in perennial allergic rhinitis: a lectin histopathological study

CONCLUSIONS: The data show that differences in the concentrations of glycoconjugates of patients with perennial allergic rhinitis (PAR) and normal controls are modest, thus indicating that the composition of the mucus in allergic patients largely resembles that of healthy individuals. The findings may point to the need for volume reduction methods controlling mucus production in patients with PAR. OBJECTIVES: We aimed to study the composition and concentration of inferior turbinate glycoconjugates of patients with PAR. MATERIALS AND METHODS: Six specific oligosaccharides found in the inferior turbinate mucosa were stained with a battery of 10 lectins. The samples recruited for study were 15 sections from patients with PAR and 17 from healthy individuals who had no nasal disease and underwent rhinoplasty surgery for cosmetic reasons. Both groups were matched for age (p = 0.208). Results. No significant difference in the concentration of galactose, fucose, sialic acid, N-acetylglucosamine, and N-acetylgalactosamine in the epithelium and submucosal glands of the inferior turbinate was found between the groups. Likewise, neuraminidase digestion of peripheral sialic acid revealed similar concentration of the penultimate galactose residue. The only significant difference was a higher concentration of mannose in submucosal serous glands of patients with PAR compared with normal controls (p = 0.04).     

A characteristic protein in nasal discharge differentiating non-allergic chronic rhinosinusitis from allergic rhinitis

To differentiate non-allergic chronic rhinosinusitis (vasomotor rhinitis) from allergic rhinitis, a characteristic protein in the nasal discharge was studied. The subjects consisted of 10 patients with perennial allergic rhinitis to house dust, 10 patients without perennial rhinitis without antigen (clinically defined as non-allergic chronic rhinosinusitis) and 5 normal volunteers without nasal disease as a control group. The total protein in the nasal discharge was determined by Lowry's method and analysis of the protein components was made by SDS-PAGE. It was found that the nasal discharge obtained from the case with perennial allergic rhinitis contained a high concentration of albumin (25.9 micrograms/ml) and a characteristic protein band with an estimated molecular weight of 26 kilo-Daltons (kD) on a SDS-PAGE, in a concentration of 15.8 micrograms/ml. In contrast, the nasal discharge from non-allergic chronic rhinosonusitis patients contained a lower concentration of albumin (12.9 micrograms/ml) than that of the allergic rhinitis patients, and the concentration of the characteristic protein 26 kD was only 2.3 micrograms/ml. The 26 kD protein was considered to originate from the nasal glands, since its secretion could be provoked by stimulation of the nasal glands of the normal volunteers with a 1% pilocarpine spray. The low concentration of albumin and the characteristic protein 26 kD in the nasal discharge thus appeared to differentiate patients with non-allergic chronic rhinosinusitis from those with perennial allergic rhinitis.     

细胞黏附分子及一氧化氮合酶在变应性鼻炎鼻黏膜中的表达

目的:对细胞黏附分子(CAM)及一氧化氮合酶(NOS)进行原位观察,探讨它们在变应性鼻炎(AR)发病中的作用。方法:采用链霉卵白素-生物素复合体(SABC)法,对AR患者及对照组手术切除的下鼻甲黏膜内细胞间黏附分子-1(ICAM-1)、血管CAM-1(VCAM-1)和淋巴细胞功能相关抗原-1(LFA-1),以及神经型NOS(nNOS)、诱导型NOS(iNOS)和内皮细胞型NOS(eNOS)进行原位检测。结果:AR下鼻甲黏膜内3种CAM表达的阳性细胞数ICAM-1为[(14.4±2.2)个/HP(×400),以下同],LFA-1为(17.2±3.3)个/HP,VCAM-1为(11.5±2.7)个/HP;对照组下鼻甲黏膜内3种CAM表达的阳性细胞数ICAM-1为(8.7±1.8)个/HP,LFA-1为(10.3±2.1)个/HP,VCAM-1为(6.9±1.8)个/HP。t值分别是11.57,10.02和8.07(均P<0.01)。AR及对照组下鼻甲黏膜内nNOS表达的阳性细胞数分别为(9.4±1.7)个/HP和(4.7±1.3)个/HP,t值为12.62,(P<0.01);iNOS表达的阳性细胞数分别为(27.5±3.2)个/HP和(4.3±1.7)个/HP,t值为36.03(P<0.01)。eNOS表达的阳性细胞数分别为(6.5±2.1)个/HP,(6.2±1.9)个/HP,t值为0.62(P>0.05)。结论:CAM在黏膜上皮、腺上皮、血管内皮以及黏膜下的各种炎性细胞等的表达,说明CAM参与AR的发生、发展。nNOS和iNOS在AR的发病过程中可能起重要作用。     

Vascular endothelial growth factor produced in nasal glands of perennial allergic rhinitis

BACKGROUND: Vascular endothelial growth factor (VEGF), a pleiotropic polypeptide that mediates endothelial cell-specific responses such as induction of angiogenesis and vascular leakage, is hyperproduced in a variety of inflammatory disorders. In asthma, VEGF hyperproduction promotes mucosal edema by enhancing vascular leakage. However, in allergic rhinitis, details of the pathophysiological importance remain unclear. This study was designed to investigate and discuss the pathophysiological significance of VEGF in nasal secretions from perennial allergic rhinitis sufferers. METHODS: Seven allergic rhinitis patients sensitized with house-dust mites and 12 chronic rhinosinusitis patients were enrolled. Nasal secretion VEGF was quantified and compared between groups. In allergic rhinitis cases, nasal lavage VEGF was estimated before and after the antigen provocation. Nasal gland VEGF was immunohistochemically investigated. VEGF messenger RNA (mRNA) levels in serous and mucous acini were analyzed by laser microdissection and light cycler-polymerase chain reaction. RESULTS: VEGF levels in nasal secretions and nasal lavage from allergic rhinitis were higher than in nonallergic rhinosinusitis, after rather than before antigen provocation. VEGF mRNA expression was higher in serous versus mucous acini. These results are consistent with the immunohistochemistry results. CONCLUSION: In allergic rhinitis, there was significant VEGF production in serous acini, which was hypersecreted after antigen provocation. VEGF may play an important role in pathophysiology of allergic rhinitis.     

Functional inferior turbinosurgery (FITS) for the treatment of resistant chronic rhinitis

CONCLUSIONS: Modified vidian neurectomy combined with inferior turbinoplasty provided an optimal surgical outcome as a treatment for intractable chronic rhinitis as evidenced by a relatively long-term follow-up. OBJECTIVE: The study was designed to determine the efficacy of submucosal reduction of the inferior turbinate and resection of the posterior nasal nerve for the treatment of resistant chronic rhinitis. PATIENTS AND METHODS: Fifty-six consecutive patients (37 males and 19 females; mean+/-SD age, 26+/-11 years) with resistant allergic rhinitis or nonallergic rhinitis with eosinophilia syndrome despite medical treatment. Symptomatic improvement including nasal obstruction, nasal discharge, sneezing, smell perception, and quality of life and objective evaluation of nasal airway resistance and nasal provocation test before and after surgery were investigated. RESULTS: The patients showed a remarkable improvement of > or = 80%, with the exception of two patients who had an approximately 50% reduction of the total symptomatic scores. Four of eight patients with anosmia subjectively improved whereas the other four patients felt unchanged. All patients who underwent rhinomanometry (n=15) and nasal provocation testing (n = 15) both before and after surgery showed a significant improvement. There were no intraoperative complications. Postoperative epistaxis occurred in one patient. One patient complained of a transient hypesthesia of the soft palate and dry eye. Nasal mucosal tears were observed in approximately 30% of the patients who otherwise showed no severe synechia or persistent crusting.     

Distribution of specific binding sites for cysteinyl leukotriene 1 receptor antagonist in human nasal mucosa

CONCLUSION: The high density of [3H]-pranlukast binding sites on the local leukocytes in human nasal mucosa suggests that CysLT1 receptor antagonists may directly modulate cellular function of the local leukocytes through binding to CysLT1 receptor on allergic nasal mucosa. OBJECTIVES: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that two classes of receptors named CysLT1 and CysLT2 receptor exist. The former is sensitive to the CysLT1 receptor antagonist currently used to treat asthma and allergic rhinitis. To confirm the binding sites of CysLT1 receptor antagonist in human nasal mucosa, the autoradiographic distribution of CysLT1 receptor was studied in human nasal inferior turbinates. MATERIALS AND METHODS: Cryostat sections were incubated with [3H]-pranlukast for autoradiography. Nonspecific binding was determined by adding unlabelled pranlukast. RESULTS: Autoradiograms indicated [3H]-pranlukast densely labeled on the interstitial cells. Blood vessels were sparsely labeled. There was no specific labeling in the submucosal glands or epithelium. These results support our previous report from in situ hybridization and immunohistochemistry of CysLT1 receptor.     

Histopathological verification of clinical indications to partial inferior turbinectomy.

Surgical treatment in cases where disturbances of the nasal patency causes changes in the nasal inferior turbinates is controversial. The authors performed light- and electron microscopy and morphometric examinations of the mucous membrane of the nasal inferior turbinates obtained after partial inferior turbinectomy in patients with vasomotor and perennial allergic rhinitis and compensation hypertrophy of the nasal inferior turbinate accompanied by nasal deviation of the septum. In specimens obtained from patients with vasomotor rhinitis, a small number of glands and fibrosis of the lamina propria was observed. In specimens obtained from perennial allergic rhinitis patients, plenty of glands and large oedema was observed. In the group with compensatory hypertrophy of the inferior turbinate, normal glands and fibred areas around the vessels were observed. The largest histopathological changes of degeneration and hypertrophy of the nasal mucosa were observed in vasomotor rhinitis patients. Histopathological examination of nasal mucosa slides confirmed the usefulness of a partial inferior turbinectomy, but only in vasomotor rhinitis patients.