[The auxiliary diagnostic value of ECP and MPO expression in nasal secretions in different types of rhinitis].

Objective:To evaluate the expression of eosinophil cationic protein and myeloperoxidase in nasal secretions in different types of rhinitis, and to explore their values in the differential diagnosis of different types of rhinitis. Methods:Six hundred and eighty-four subjects were selected, including 62 subjects in the acute rhinitis group, 378 subjects in the allergic rhinitis group, 94 subjects in the vasomotor rhinitis group, 70 subjects in the eosinophilic non-allergic rhinitis group, and 80 subjects in the control group. Nasal secretion samples were collected from the five groups, and the percentages of inflammatory cells were counted by Rachel's staining, and the expression of ECP/MPO was detected by colloidal gold assay. The correlation between the clinical diagnosis, the inflammatory cells in the nasal secretions and the expression of ECP/MPO was analyzed. Results:Nasal cytological smears showed that compared with the control group, the percentage of eosinophils in the AR and NARES groups were significantly higher （P<0.05）, while the percentage of neutrophils was not different （P>0.05）; the percentage of neutrophils was significantly higher in the acute rhinitis group compared with the control group （P<0.05）, while the percentage of eosinophils was not statistically different （P>0.05）; in vasomotor rhinitis group, the eosinophils and neutrophils were not statistically different compared with the control group（P> 0.05）. The colloidal gold results showed that there were differences in the expression of ECP/MPO in different types of rhinitis, among which 49 cases （79.0%） in the acute rhinitis group expressed ECP+/MPO+; 267 cases （70.6%） in the AR group and 56 cases （75.7%） in the NARES group expressed ECP+/MPO-; 80 cases （85.1%） in the vasomotor rhinitis group and 69 cases （86.3%） in the control group expressed ECP-/MPO-. Conclusion:The differences in ECP and MPO expression between different types of rhinitis have certain reference value for the differential diagnosis of different types of rhinitis and the selection of treatment programs.

A Pilot Study Investigating Clinical Responses and Biological Pathways of Azelastine/Fluticasone in Nonallergic Vasomotor Rhinitis before and after Cold Dry Air Provocation.

BACKGROUND: Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers. METHODS: To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14°C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu (n = 20) or placebo (n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post-CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post-CDA challenge at each visit. RESULTS: The minimum cross-sectional area (p < 0.05), cough count (p < 0.05), and substance P (p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment. CONCLUSIONS: This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly.

[The disturbances of vegetative homeostasis in the children suffering from vasomotor rhinitis].

The objective of the present work was to study the state of the vegetative homeostasis in 157 children presenting with vasomotor rhinitis. It was shown that the children with this pathology suffer from vegetative dysfunction. The forms of this disorder are various which require the mulidisciplinary approach to their diagnostics and treatment.

Determination of oxidative stress and effect of erdosteine on rhinitis medicamentosa in a rat model.

We aimed to determine the presence of oxidative stress in rhinitis medicamentosa (RM) and to evaluate the effect of erdosteine (ED) on mucosal changes in a rat model. Twenty-four male rats were used in this experimental study. Three groups were created. Group 1 (n=8) was the control group. Two puffs of 0.05% oxymetazolin were sprayed into the nasal cavities of the remaining rats (n=16) three times daily for eight weeks. One of these 16 rats was scarified at the end of the eight weeks and examined to confirm the presence of RM. Seven of the remaining 16 rats were killed, and venous blood samples were taken (Group 2). Group 3 (n=8) received 10mg/kg of an ED suspension orally for seven days. All rats were put on formalin for light microscopy. The total antioxidant status (TAS) was similar in all groups (p=0.073). The total oxidative status (TOS) of the RM group was significantly higher than that of the control group and RM+ED group (Group 3) (p=0.003 and p=0.011, respectively). The pathological recovery of the nasal mucosa of the rats was similar in the RM+ED and control groups. The TOS was high in this RM rat model, and oxidative stress was associated with RM. ED significantly ameliorated nasal mucosal changes induced by RM, suggesting that oxidative stress may play an important role in the pathophysiology of this condition.

Pharmacological evaluation of selective α2c-adrenergic agonists in experimental animal models of nasal congestion.

Nasal congestion is one of the most troublesome symptoms of many upper airways diseases. We characterized the effect of selective α2c-adrenergic agonists in animal models of nasal congestion. In porcine mucosa tissue, compound A and compound B contracted nasal veins with only modest effects on arteries. In in vivo experiments, we examined the nasal decongestant dose-response characteristics, pharmacokinetic/pharmacodynamic relationship, duration of action, potential development of tolerance, and topical efficacy of α2c-adrenergic agonists. Acoustic rhinometry was used to determine nasal cavity dimensions following intranasal compound 48/80 (1%, 75 µl). In feline experiments, compound 48/80 decreased nasal cavity volume and minimum cross-sectional areas by 77% and 40%, respectively. Oral administration of compound A (0.1-3.0 mg/kg), compound B (0.3-5.0 mg/kg), and d-pseudoephedrine (0.3 and 1.0 mg/kg) produced dose-dependent decongestion. Unlike d-pseudoephedrine, compounds A and B did not alter systolic blood pressure. The plasma exposure of compound A to produce a robust decongestion (EC(80)) was 500 nM, which related well to the duration of action of approximately 4.0 hours. No tolerance to the decongestant effect of compound A (1.0 mg/kg p.o.) was observed. To study the topical efficacies of compounds A and B, the drugs were given topically 30 minutes after compound 48/80 (a therapeutic paradigm) where both agents reversed nasal congestion. Finally, nasal-decongestive activity was confirmed in the dog. We demonstrate that α2c-adrenergic agonists behave as nasal decongestants without cardiovascular actions in animal models of upper airway congestion.

[The roles of three peptides in the pathogenesis of vasomotor rhinitis].

OBJECTIVE: To explore the possible roles of three neuropeptides in the pathogenesis of vasomotor rhinitis by studying the expression and distribution of neuropeptides in the mucosa of vasomotor rhinitis, such as Substance P(SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide(VIP). METHOD: The mucosa specimens of thirty vasomotor rhinitis patients who had typical symptoms and signs were selected randomly as the experiment group and were divided into two subgroups depending on if received treatment or not. While the normal middle turbinate mucosa specimens of nine cases were selected as the control group. The expression and distribution of neuropeptides were examined by immunohistochemical SP method and computer image disposing and analyzing system. RESULT: The terminals of SP, CGRP and VIP in the treated experiment group wer and untreated experiment group were markedly increased in density of immunostaining compared to the control group,and the difference is significant (P < 0.01). CONCLUSION: Neuropeptides, such as SP, CGRP and VIP, may play important roles in the pathophysiological mechanism of vasomotor rhinitis.

Intrapharyngeal distribution of gastric acid refluxate.

OBJECTIVES/HYPOTHESIS: Determination of intrapharyngeal distribution of gastric acid refluxate is needed to better understand the pathogenesis of reflux-attributed aerodigestive tract disorders. The aims of the study were to determine intrapharyngeal distribution of gastric acid refluxate and to determine whether this distribution can better differentiate patients from control subjects compared with data obtained from a single hypopharyngeal site. METHODS: We prospectively studied 10 healthy volunteers, 12 patients with reflux laryngitis, and 15 patients with vasomotor rhinitis using a concurrent dual pharyngeal/dual esophageal pH recording technique. We determined the hypopharyngeal and oropharyngeal pH profile, including number, duration, and distribution of reflux events irrespective of and in correlation with intraesophageal pH profile using four different pH thresholds. RESULTS: Few drops in pharyngeal pH were found to be true reflux events based on their correlation with esophageal pH events. For the pharyngeal pH threshold criterion of a drop to 4.0 or less, 6 of 12 patients with reflux laryngitis, 5 of 15 patients with vasomotor rhinitis, and 2 of 10 normal control subjects exhibited a total of 25 (range, 1-5) distal pharyngeal acid reflux events. Overall, 34% of these events reached the oropharyngeal pH recording site. Between-group comparison for all levels of pH threshold criteria did not show any significant difference of reflux parameters in the hypopharyngeal or in the oropharyngeal sites among the studied groups. CONCLUSIONS: Reflux of gastric acid into the pharynx may extend to the region of the oropharynx in both patients and control subjects. Overall distribution of acid refluxate to the oropharynx is low but as groups is similar between healthy individuals and patients with reflux laryngitis and those with vasomotor rhinitis. Parameters of oropharyngeal acid reflux such as number and duration do not differentiate patients from control subjects.

Pathophysiological features of the nasal mucosa in patients with idiopathic rhinitis compared to allergic rhinitis.

BACKGROUND: The literature on abnormality of vasomotor responses of the nasal mucosa to cold stimulation of the skin in idiopathic rhinitis is conflicting. The objective of this study was to elucidate pathophysiological features of the nasal mucosa in idiopathic rhinitis compared to allergic rhinitis. METHODS: The following were studied in patients with idiopathic rhinitis and allergic rhinitis and in normal controls: (1) threshold of the nasal reaction to histamine; (2) inflammatory cells in nasal lavage and scraped nasal mucosal epithelium, and (3) nasal vasomotor response to cold stimulation of the feet evaluated by acoustic rhinometry. RESULTS: Inflammatory cells were not found to be involved in idiopathic rhinitis. Nasal reactivity to histamine was significantly enhanced in patients with idiopathic rhinitis compared to normal controls, but was significantly lower compared to those with allergic rhinitis. The most prominent finding in idiopathic rhinitis was nasal mucosal swelling induced by cold stimulation of the feet. While in normal controls, cold stimulation of the feet caused mucosal contraction due to sympathetic excitation, sympathetic nasal vasomotor response in idiopathic rhinitis patients was significantly inhibited and caused mucosal swelling and enhanced nasal secretion. Mucosal reactions observed in allergic rhinitis were between those observed in idiopathic rhinitis and in normal controls. Cold stimulation of the feet increased systolic blood pressure by 5-15 mm Hg, but the degree of increase observed in the 3 groups was almost equal. CONCLUSIONS: The above findings indicate that patients with idiopathic rhinitis have abnormalities that inhibit sympathetic reactions and enhance parasympathetic vasomotor response at peripheral levels, possibly in the nasal mucosa.

Alterations of muscarinic acetylcholine receptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals.

Cholinergic nasal hyperresponsiveness in nasal allergy may be due to changes of the characteristics in muscarinic cholinergic receptors. Radioligand receptor binding and in vitro autoradiographic studies of nasal mucosa in nonallergic (NA) and allergic patients were performed to investigate this hypothesis. The heterogeneous NA group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis. The 3H-(-)-Quinuclidinylbenzilate binding to muscarinic receptors in human nasal mucosa membranes was saturable and of high affinity in all groups. No significant differences could be demonstrated between the subgroups of the NA patients. In allergic patients the dissociation constants and receptor densities were significantly decreased in comparison with those of NA and with those of control individuals. No differences in agonist binding or coupling of the muscarinic receptor to the effector system via the G protein could be observed in allergic patients. In vitro autoradiographic experiments demonstrated specific 3H-(-)-Quinuclidinylbenzilate labeling of the glandular acini in NA and allergic patients. No specific labeling could be observed in the epithelium, blood vessels, or connective tissue. In conclusion, the increased sensitivity and decreased muscarinic receptor number may reflect the cholinergic-induced hypersecretion in nasal allergy but are probably too small to explain the complex allergic reaction.

Alterations of adrenoceptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals.

Nasal hyperreactivity in nasal allergy may be due to changes of the characteristics in adrenergic receptors. Radioligand receptor-binding studies with the antagonists, 3H-prazosin (alpha 1-adrenoceptor), 3H-rauwolscine (alpha 2-adrenoceptor), and 125I-(-)-Cyanopindolol (beta-adrenoceptor) were performed in homogenates of nasal mucosa of allergic and nonallergic (NA) patients to investigate this hypothesis. The heterogeneous NA group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis. No significant differences in affinities or densities of alpha 1- and alpha 2-adrenoceptors could be demonstrated in allergic patients in comparison with NA and control individuals. The beta-adrenoceptor density was significantly reduced in allergic patients in comparison with that of control individuals. Neither changes in agonist binding or in the effect of Gpp(NH)p on the agonist binding to beta-adrenoceptors could be observed in allergic patients. The subtype selective antagonist, LK203-030, demonstrated the presence of a homogeneous population of beta 2-adrenoceptors in human nasal mucosa of both NA and allergic patients. In vitro, autoradiography demonstrated specific 125I-(-)-Cyanopindolol labeling of the epithelium in NA and allergic patients. In conclusion, no changes in characteristics of alpha 1- or alpha 2-adrenoceptors in the nasal mucosa could be demonstrated in nasal allergy. However, a decreased number of beta-adrenoceptors may reflect a beta-adrenergic abnormality in nasal allergy.

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa.

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components. The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation. The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.

Histamine H1 receptors and affinity analyses in human nasal mucosa in cases of nasal allergy.

An increased number (density) or sensitivity (affinity) of histamine H1 receptors could cause an increase of allergic symptoms. Using the specific H1 receptor blocker 3H-mepyramine, we have demonstrated for the first time an H1 receptor number (Bmax) and a binding affinity (Kd) in guinea pig and human nasal mucosa. H1 antihistamines inhibited that 3H-mepyramine binding sites represent H1 receptors in nasal mucosa. Bmax and Kd values were not significantly different among the nonallergic sinusitis, vasomotor rhinitis, or the nasal allergy group, suggesting that H1 receptors do not change quantitatively and qualitatively in allergic nasal mucosa. There was no significant correlation between H1 receptor number and clinical data (IgE, peripheral eosinophils, RAST). These data suggest that H1 receptor number and affinity are not main etiological and pathophysiological factors in nasal allergy.