To investigate soluble IL-2 receptor (sIL-2R) levels in nasal allergy, the sera and nasal secretions from patients with nasal allergy and from healthy subjects were subjected to a double-epitope enzyme-linked immunosorbent assay. Significant elevation of sIL-2R concentrations in the sera and nasal secretions was observed in the allergy patients (n = 26) compared with those of healthy subjects (n = 9). IL-2R-positive (CD25+) cells were observed in the crust formed in an allergic nasal mucosa. The concentration of sIL-2R in the sera correlated neither with the eosinophil count of the peripheral blood count nor with clinical severity. The concentration of sIL-2R in the nasal secretions was significantly higher compared with that in the sera from allergic patients (p < 0.01), whereas no significant difference was observed between sIL-2R levels in the sera and nasal sections from normal subjects. These findings indicate that sIL-2R plays an essential role in allergic processes by regulating IL-2R-positive cells recruited into the nasal mucosa.
1). To be able to recognize allergic fungal sinusitis (AFS), a common and underdiagnosed condition.
A 28 years old man presented with yet another flare up of chronic sinusitis (he also had a history of allergic rhinitis), complaining of impaired taste and smell, itching in ears, and minimal epistaxis—mainly on the right side—after blowing his nose. The physical exam revealed a hyperemic nasal mucosa smeared with bright red blood and covered with yellowish crusts. The right inferior turbinate was pink and swollen. Investigations: skin prick test for Curvularia lunata was positive, white blood cell count was 7.700, with 9% eosinophils (with an absolute eosinophil count of 704), radio-allergo-sorbent test for Curvularia lunata was positive, total serum immunoglobulin E was 1926 IU/ml, serum eosinophilic cationic protein was 80 micrograms/l. A CT scan of the sinuses revealed pansinusitis and a soft tissue process (with multiple areas of calcification) in the right maxillary sinus eroding through the supero-medial wall into the right orbit. The patient was treated surgically. Analysis of debrided tissue revealed on histology large amounts of eosinophil-rich mucoid material, necrosis and bone remodeling. The bacterial smears and tissue cultures were negative. The silver impregnation stain revealed fungal short hyphal elements. Tissue fungal cultures grew Curvularia lunata.
Although responsible for many cases of chronic rhino-sinusitis, AFS is heavily underdiagnosed. We present a case with some unusual features. Our patient had AFS, which tends to affect patients with significant immune deficiencies (our patient was immunocompetent).
The invasion into orbit (usually a disastrous complication) was discovered only as accidental finding on a CT scan.
Positive radioallergosorbent test (RAST) results, skin test results, or presence of serum precipitins for fungal allergens, in combination with fungal culture results that match that particular fungal species, are crucial in making a diagnosis of allergic fungal sinusitis.
Some believe that allergic fungal sinusitis may be a trigger of chronic rhinosinusitis in up to 93% of cases. Taking into consideration the lack of specificity of nasal eosinophilia, and the ubiquicity of fungal colonization of the nose, it has been proposed to apply the term AFS only to those patients with chronic rhinosinusitis that fulfill the above criteria. Therapy is surgical.
Objective and design
This study is aimed at exploring the role of neurokinin-1 receptor (NK-1R) in the development of allergic rhinitis (AR) in rats.
Sprague–Dawley rats were sensitized and challenged with ovalbumin to induce AR. The rats were treated intranasally with saline, control, or NK-1R-specific small interfering RNA (siRNA) before and during the challenge period. The numbers of sneezes and nose rubs and amount of nasal secretion in individual rats were measured. The levels of NK-1R expression in the nasal mucosal tissues after the last challenge were determined. The numbers of eosinophils in the collected nasal lavage fluid and the levels of serum interleukin (IL)-5 in individual rats were determined.
The levels of NK-1R expression in the nasal mucosal tissues of the AR rats that had been treated with saline or control siRNA were significantly higher than those in the healthy controls and the rats treated with NK-1R-specific siRNA, demonstrating NK-1R silencing. Furthermore, knockdown of NK-1R expression significantly reduced the amounts of sneezing, nose rubbing, and nasal secretions in AR rats. Knockdown of NK-1R expression also significantly eliminated eosinophil infiltration in the nasal tissues and reduced the levels of serum IL-5 in rats.
Knockdown of NK-1R expression decreased allergic inflammation in nasal mucosal tissues and alleviated the allergic rhinitis symptoms, suggesting that NK-1R may be a critical mediator of the development of AR.
Allergic rhinitis; NK-1R; siRNA; Rats
Nasal congestion is a common symptom in rhinitis (both allergic and nonallergic), rhinosinusitis and nasal polyposis. Congestion can also be caused by physical obstruction of nasal passages and/or modulation of sensory perception. Mucosal inflammation underlies many of the specific and interrelated factors that contribute to nasal congestion, as well as other symptoms of both allergic rhinitis and rhinosinusitis. A wide range of biologically active agents (eg, histamine, tumor necrosis factor-α, interleukins, cell adhesion molecules) and cell types contribute to inflammation, which can manifest as venous engorgement, increased nasal secretions and tissue swelling/edema, ultimately leading to impaired airflow and the sensation of nasal congestion. Inflammation-induced changes in the properties of sensory afferents (eg, expression of peptides and receptors) that innervate the nose can also contribute to altered sensory perception, which may result in a subjective feeling of congestion. Increased understanding of the mechanisms underlying inflammation can facilitate improved treatment selection and the development of new therapies for congestion.
allergic rhinitis; congestion; obstruction; pathophysiology; rhinosinusitis
In the allergic mucosa, there is a significant increase in numbers of CD25+ cells and activated eosinophils. To determine whether a link exists between the activated T-lymphocytes and tissue eosinophils in nasal allergy, we studied CD25+ cells in the nasal mucosa and compared the levels of soluble IL-2 receptor (sIL-2R) both in the serum and the nasal secretions, and further investigated expression of CD11b on eosinophils in the nasal lavage fluids and peripheral blood of patients with nasal allergy. We also examined the effects of the culture supernatant of Con A- and IL-2-activated T-lymphocytes on CD11b expression on eosinophils in the present study. The concentration of sIL-2R in the nasal secretions from patients with Japanese cedar pollinosis (JCP) was significantly higher than that from normal subjects (p < 0.01). The sIL-2R level was significantly higher in the nasal secretions than in the sera in patients (p < 0.01), and CD11b expression on eosinophils from nasal hvage fluid was significandy higher than that of eosinophils from peripheral blood of the same individuals (p < 0.01). The activated T-lymphocytes promoted eosinophil activation with upregulation of CD11b in vitro, and eosinophils in the nasal secretions from patients significantly expressed more CD11b in vivo. These results indicate that activation of T-lymphocytes is linked to eosinophil activation in nasal allergy.
Capsaicin is the spice component of red pepper. It can be easily inhaled, inducing a reproducible cough and provokes a secretory response from the human nasal mucosa. To date, there has been no report of occupational rhinitis (OR) caused by capsaicin. We report the case of a 44-year-old female mill worker who developed occupational rhinitis after 4 years of exposure to capsaicin. She developed nasal congestion, rhinorrhea, and itchy nose, which were all aggravated upon exposure at the workplace. The patient had negative responses to all common inhalant allergens, including capsaicin, by skin prick tests. The nasal provocation test with capsaicin showed that the nasal symptom score and eosinophil count increased 10 minutes after the provocation and decreased after 1 to 3 hours; no significant response was noted to house dust mite allergen. The patient's work-related rhinitis improved 1 month after she relocated and started pharmacological treatment. To our knowledge, this is the first case of OR caused by capsaicin exposure in the workplace. We provide evidence suggesting that OR may be mediated by a non-immunological mechanism.
Occupational rhinitis; capsaicin
Treatment with beclomethasone dipropionate aerosol (BDA), 50 mug four times daily in each nostril, was compared with placebo therapy in a double-blind non-crossover trial of 30 matched patients with allergic rhinitis induced by ragweed pollen. The trial was started at the beginning of the ragweed season and continued for 42 days. Response to treatment was assessed from information on daily diary cards, weekly objective measurements of nasal patency and measurement of total eosinophil count (TEC) before treatment and at week 4. Patients in the BDA group had significantly less (P less than 0.05) sneezing, rhinorrhea and nasal stuffiness at 36 days, cough at 10 days and antihistamine consumption at 17 days. There was no significant difference between the groups in eye symptoms, nasal airway inspiratory resistance, maximum inspiratory nasal flow or TEC. Overall comparison with previous pollen seasons by the patients indicated moderate to great improvement in 86% of the BDA group and in 13% of the placebo group (P less than 0.01). Minor side effects were noted by two patients in each group.
Eosinophilic inflammation is a hallmark of chronic rhinosinusitis with nasal polyps. To model this disease process experimentally, nasal sensitization of mice with ovalbumin or aspergillus has been described. Here, we describe a genetically mutant mouse that develops robust spontaneous nasal eosinophilic inflammation. These mice lack the enzyme SHP-1 that down-regulates the IL-4Rα/stat6 signaling pathway. We compared nasal inflammation and inflammatory mediators in SHP-1 deficient mice (mev) and an ovalbumin-induced nasal allergy model.
A novel technique of trans-pharyngeal nasal lavage was developed to obtain samples of inflammatory cells from the nasal passages of allergic and mev mice. Total and differential cell counts were performed on cytospin preparations. Expression of tissue mRNA for IL-4, IL-13, and mouse beta-defensin-1 (MBD-1) was determined by quantitative PCR. Eotaxin in the lavage fluid was assessed by ELISA.
Allergic and mev mice had increased total cells and eosinophils compared with controls. Expression of IL-4 was similarly increased in both allergic and mev mice, but expression of IL-13 and eotaxin was significantly greater in the allergic mice than mev mice. Eotaxin was significantly up-regulated in both allergic rhinitis and mev mice. In both models of eosinophilic inflammation, down-regulation of the innate immune marker MBD-1 was observed.
The mev mice display spontaneous chronic nasal eosinophilic inflammation with potential utility for chronic rhinosinusitis with nasal polyps research. The eosinophilic infiltrate is more robust in the mev mice than allergic mice, but Th2 cytokine expression is not as pronounced. Decreased MBD-1 expression in both models supports the concept that Th2-cytokines down-regulate sinonasal innate immunity in humans, and suggests a role for mouse models in investigating the interaction between adaptive and innate immunity in the sinonasal mucosa.
The evolution of nasal inflammation during a common cold in patients with nasal polyposis under topical steroid treatment is not clearly defined in the literature. Objective of this study was to analyse nasal inflammation during a common cold in patients with nasal polyposis under topical steroid treatment in comparison with control subjects. Two groups of subjects (35 consecutive patients with nasal polyposis receiving medical treatment, and 17 control subjects without any symptoms of chronic rhino-sinusitis) were studied: 10 patients with nasal polyposis and 11 controls had a common cold during a one-year follow-up period. Nasal lavage was performed at baseline and during the common cold. Soluble inflammatory mediators and permeability markers were determined in the nasal lavage fluid, as well as total and differential counts of the cells present. At baseline, no significant difference between controls and patients was observed, except for eosinophils. Paired comparisons between baseline and cold in controls revealed that all measured parameters, except for eosinophils, increased in the second nasal lavage. In nasal polyposis patients, the total cell neutrophil counts tended to increase. However, most of the concentrations of soluble parameters did not vary significantly in the second lavage, except for interleukin-6. In conclusion nasal inflammation markers appear to be similar in patients with and without nasal polyposis during a common cold when nasal polyposis patients are under topical steroid treatment.
Nose; Common cold; Nasal polyposis; Therapy
Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps.
Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control.
Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone.
These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone.
Previous studies of inflammation in allergic rhinitis using nasal irrigation have been unsatisfactory because of 1) poor reproducibility; 2) the tendency of irrigation to overdilute mediators; and 3) the failure of this technique to evaluate interstitial concentrations of relevant mediators. For this study we used filter paper as a matrix to collect nasal secretions in patients undergoing nasal antigen challenge.
To evaluate inflammatory mediators of allergen-induced rhinitis during a clinical trial of fexofenadine.
Subjects evaluated at a referral medical center were placed on traditional dosing of fexofenadine at 60 mg, twice daily, or placebo in a double-blind, crossover fashion for 1 week before the nasal challenge. Nasal challenge was performed with nasal insufflation of either 1,000 AU timothy or 0.1 mL ragweed (1:100 wt/vol) extract outside the pollen season. Nasal secretions were collected at baseline and then at 2, 4, and 6 hours after nasal challenge. Secretions were evaluated for expression of the cellular adhesion molecule-1, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, macrophage inflammatory protein (MIP)-1α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using commercially available enzyme-linked immunoadsorbent assay kits. Patients’ symptom scores were evaluated during the nasal challenge.
Significantly (P < 0.05) increased peak levels of TNF-α, IL-4, IL-10, and MIP-1α were detected after antigen challenge as compared with baseline levels. There was a nonsignificant trend toward an increase in GM-CSF after antigen challenge (P = 0.07). There was no difference in the peak levels of TNF-α, IL-4, IL-10, MIP-1α, or GM-CSF measured when patients were on fexofenadine versus placebo. Finally, there were no significant differences in patients’ symptom scores during antigen challenge when subjects were on fexofenadine versus placebo.
Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.
Nasal eosinophilia is one of the potential tests for substantiating the diagnosis of allergic rhinitis.
The aim was to establish the validity of nasal eosinophilia in allergic rhinitis, to study it's various clinical correlates and interpret it in context of skin sensitivity pattern.
Prospective cased study.
The patients were selected on the basis of history and clinical examination and were from the Himalayan region.
The patients and the equal number of controls, were subjected to nasal smear for eosinophilia and intra-dermal skin tests to various allergeus.
Overall, eighty percent of nasal smears were positive in various degrees among the cases. Around eighty-eight percent of cases showed both smear and skin test positivity, thereby signifying a high degree of harmony among them and further validating and confirming the diagnosis of allergic rhinitis.
Nasal eosinophilia was found to be a useful diagnostic test in allergic rhinitis, with a moderately high sensitivity and a high specificity.
Allergic rhinitis; Nasal eosinophilia; Nasal smear
TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge.
Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α2-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.
Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α2-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.
TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.
Tumour necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay and eosinophil cationic protein (ECP) by radio-immunoassay to evaluate TNF-α in nasal allergy. There was no significant difference either between the mean concentrations of TNF-α in nasal secretions from the patients with perennial nasal allergy and those of normal subjects, or between the TNF-α and ECP concentrations. However, reverse transcription polymerase chain reaction showed a specific increase of TNF-α mRNA and IFN-γ mRNA in allergic nasal mucosa after allergen challenge in vitro. These findings suggest a possibility that T cell-derived IFN-γ up-regulates macrophages to elaborate TNF-α, which may play a role in amplifying allergic inflammation in the nose through the cytokine network.
provocation with adenosine 5'-monophosphate (AMP) elicits nasal
symptoms in subjects with rhinitis. Histamine released from mast cells
may play a part in AMP induced nasal responses.
rhinitis were recorded and histamine release in the fluid obtained by
nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo
instillations was measured in nine subjects with allergic rhinitis and
nine non-allergic controls in a double blind, randomised, placebo
RESULTS—No symptoms or
significant increases in histamine were observed after GMP and placebo
challenge. Significantly higher levels of histamine were seen in the
nasal lavage fluids of allergic subjects following AMP challenge than
in non-allergic controls, the median (range) histamine concentration
increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels
was seen in the non-allergic subjects in whom the median histamine
concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge.
elicits an immediate rise in histamine levels in the nasal lavage fluid
of allergic subjects compared with non-allergic individuals. These
findings indicate that the exaggerated nasal response to adenosine may
reflect mast cell priming in vivo, thus supporting its application as a
potential new marker of allergic inflammation.
Aim of the study was to evaluate the effect of a 2-year course of subcutaneous specific immunotherapy or continuous oral antihistamine treatment on the eosinophilic inflammation in nasal secretions of patients with severe persistent allergic rhinitis caused by house dust-mites. After informed consent, 31 rhinitis patients, sensitive to dust-mite antigens, were enrolled: 12 were randomly assigned to specific immunotherapy (group A), 11 to continuous oral antihistamine (cetirizine) treatment (group B), and 8 to an oral antihistamine (cetirizine) on demand (group C). Nasal scrapings were performed with a cotton-tipped swab and cells counted before and after 24 months of therapy. Intercellular adhesion molecule-1 and eosinophil cationic protein expression in cytological smears were assessed by immunohistochemistry. All patients completed the study. The percentage of inflammatory cell types was comparable in the 3 groups at the beginning of the study. Eosinophils, identified as cells expressing eosinophil cationic protein, significantly decreased dropping to zero after 2 years of treatment in groups A and B, while no change was observed in group C. Expression of intercellular adhesion molecule-1 also decreased significantly in groups A and B, but not in group C. This decrease was associated with a significant reduction in epithelial shedding. In the 2-year period studied, specific subcutaneous immunotherapy and continuous oral antihistamine treatment were found to be effective in reducing eosinophilic infiltration and adhesion molecule expression in the nasal mucosa of patients with persistent allergic rhinitis. Furthermore, immunotherapy was more effective in controlling epithelial disruption while antihistamines appeared to be more active in controlling nasal inflammation. Both treatments induced a significant decrease in intercellular adhesion molecule-1 expression in epithelial cells and also a dramatic reduction of eosinophil cationic protein positive staining. These parameters can be considered useful means for controlling the state of persistent inflammation which is typical of persistent respiratory allergy. Nasal scraping was demonstrated to be a simple and safe procedure for monitoring some nasal inflammation parameters.
Allergic rhinitis; Medical treatment; Immunotherapy; Eosinophilic infiltration
Nasal cytology is a very useful diagnostic tool in nasal disorders, being able to detect both the cellular modifications of the nasal epithelium caused by either allergen exposure or irritative stimuli (that may be physical or chemical, acute or chronic), or inflammation. Over these past few years, nasal cytology has allowed to identify new disorders, such as the non-allergic rhinitis with eosinophils (NARES), the non-allergic rhinitis with mast cells (NARMA), the non-allergic rhinitis with neutrophils (NARNE), and the non-allergic rhinitis with eosinophils and mast cells (NARESMA). The rhinocytogram is actually able to distinguish the different forms of allergic rhinitis and to suggest the appropriate treatment, such as antinflammatory drugs or allergen immunotherapy. The technique is easy to perform and nasal cytology is therefore particularly suitable even for children. Such a consideration suggests the utility of a systematic use of nasal cytology in the diagnostic work-up of nasal disorders in children, in order to reach a proper defined diagnosis and to set a rational therapeutic approach: in facts, these two elements are fundamental in order to prevent from complications and to improve the patient’s quality of life.
Nasal cytology; Allergic rhinitis; Non-allergic rhinitis; Classification; Allergen immunotherapy
Botanical products are frequently used for treatment of nasal allergy. Three of these substances, Cinnamomum zeylanicum, Malpighia glabra, and Bidens pilosa, have been shown to have a number of anti-allergic properties in-vitro. The current study was conducted to determine the effects of these combined ingredients upon the nasal response to allergen challenge in patients with seasonal allergic rhinitis.
Twenty subjects were randomized to receive the combination botanical product, (CBP) 2 tablets three times a day, loratadine, 10 mg once a day in the morning, or placebo, using a randomized, double-blinded crossover design. Following 2 days of each treatment and during the third day of treatment, subjects underwent a nasal allergen challenge (NAC), in which nasal symptoms were assessed after each challenge dose and every 2 hours for 8 hours. Nasal lavage fluid was assessed for tryptase, prostaglandin D2, and leukotriene E4 concentrations and inflammatory cells.
Loratadine significantly reduced the total nasal symptom score during the NAC compared with placebo (P = 0.04) while the CBP did not. During the 8 hour period following NAC, loratadine and the CBP both reduced NSS compared with placebo (P = 0.034 and P = 0.029, respectively). Analysis of nasal lavage fluid demonstrated that the CBP prevented the increase in prostaglandin D2 release following NAC, while neither loratadine nor placebo had this effect. None of the treatments significantly affected tryptase or leukotriene E4 release or inflammatory cell infiltration.
The CBP significantly reduced NSS during the 8 hours following NAC and marginally inhibited the release of prostaglandin D2 into nasal lavage fluid, suggesting potential clinical utility in patients with allergic rhinitis.
BACKGROUND: It has been suggested that inhaled frusemide protects subjects with asthma against bronchoconstriction by enhancing the synthesis of prostaglandin E2 (PGE2). To evaluate this hypothesis the effect of frusemide on PGE2 production from nasal mucosa was studied. METHODS: Two main arachidonic acid metabolites produced by epithelial cells, PGE2 and 15-hydroxy 5,8,11,13-eicosatetraenoic acid (15-HETE), were measured by radioimmunoassay in nasal secretions obtained by nasal lavages with saline. Eleven healthy volunteers were randomly assigned to two study days, one week apart, in a double blind crossover study. Nasal instillation with three increasing doses of frusemide (5, 10, and 20 mg) or placebo was carried out at intervals of 15 minutes. Nasal lavages were performed immediately before nasal instillations and 15, 30, and 60 minutes after the last instillation. RESULTS: Baseline concentrations of 15-HETE were at least six times higher than PGE2. No differences between frusemide and placebo were detected either on PGE2 or 15-HETE release. CONCLUSIONS: The findings do not support the hypothesis that the antiasthmatic effect of frusemide may be due to increased synthesis of PGE2 or release in the respiratory mucosa.
Upper airway inflammation could be reflected by nasal lavage cytology test, which is characterized by advantages of non-invasive, simple, objective and costless. However, reference values nasal lavage cytology was not established. To establish reference values and positive standard for nasal lavage cytology through screening normal healthy subjects and patients with allergic rhinitis according to strict inclusion criteria.
To establish reference values and positive standard for nasal lavage cytology through screening normal healthy subjects and patients with allergic rhinitis according to strict inclusion criteria.
There was no statistical significance in gender constitutional proportion, age, height and weight among each group. 95% CI of neutrophils, eosinophils was (0∼12.61)/×200 and (0∼1.70)/×200, respectively. The median (interquartile range) of neutrophils were 0(0.65)/×200 in AR group, which showed no statistical difference (P > 0.05) with that of normal group [0(0)/×200]. A significant difference was found in the median (interquartile range) of eosinophils [6.90(22.40)/×200] in AR group as compared with that of normal control group [0(0.10)/×200, P < 0.001].
Establishment of reference values of nasal lavage cytology test is helpful to discriminate normal individuals and patients with allergic rhinitis, but also a non-invasive tool for objective reflection on upper airway inflammation, which is of great value for scientific and clinical purposes.
Alpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation.
Forty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II.
At baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II.
The increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation.
Alpha1-antitrypsin; Allergic rhinitis; Eosinophil cationic protein; IgA; Nasal lavage fluid
About half of a series of 100 consecutive patients with disturbances of the eyes, ears, nose or throat complained of postnasal drip. When smears of the mucous discharge were examined it was found that in about a third of the cases in which there was complaint of drip, neither eosinophils nor neutrophils could be demonstrated. This indicates that causes of the drip other than allergic disease and infection must be considered.
Cytologic examination of the postnasal drip showed that about one-third of the patients with nasal disease or histories positive for allergic reaction had nasal eosinophilia. Nasal eosinophilia was noted occasionally in patients with normal-appearing nasal structures and in patients with no history of allergic disease.
BACKGROUND: In the lower airways an association has been found between early phase reaction (EPR), late phase reaction (LPR), and bronchial hyperreactivity. However, this association has not been shown for the upper airways in nasal pollen challenge studies. A study was undertaken to determine whether the EPR, LPR, and nasal hyperreactivity are related in perennial allergic rhinitis. METHODS: Twenty four patients with rhinitis who were allergic to house dust mite (HDM) were challenged with HDM extract. The nasal response was monitored by symptom scores and nasal lavages for up to 9.5 hours after challenge and concentrations of albumin, tryptase, and eosinophil cationic protein (ECP) in the lavage fluid were measured. Thirteen patients (defined as dual responders) had increased symptom scores between 3.5 and 9.5 hours compared with the baseline score. The other 11 patients (defined as early responders) showed an isolated EPR only. Nasal hyperreactivity was determined by nasal histamine challenge 24 hours later. RESULTS: Dual responders showed a significantly higher symptom score, albumin influx, and tryptase release during the EPR. During the late phase (3.5-9.5 hours) albumin influx was significantly increased at most time points and ECP release was significantly higher at 9.5 hours in the dual responder group. Dual responders showed a significantly stronger response to all doses of histamine. The area under the curve (AUC) of symptom scores during EPR and LPR and the AUC of the histamine dose response were significantly correlated (EPR-LPR: r = 0.49, p < 0.01; EPR-histamine: r = 0.75, p < 0.001; LPR-histamine: r = 0.66, p < 0.001). CONCLUSIONS: In patients with perennial allergic rhinitis the nasal responses to allergen and histamine are associated. Dual responders have an increased EPR, increased levels of mediators, and increased allergen-induced hyperreactivity.
Diesel exhaust particles (DEP) have been implicated in the increased incidence of allergic airway disorders. We investigated the effects of DEP on localized immunoglobulin production by performing nasal challenges with varying doses of DEP and analyzing the local immune response in nasal lavages obtained before and after. A significant rise in nasal IgE but not IgG, IgA, IgM, or albumin was observed in subjects 4 d after challenge with 0.30 mg DEP, equivalent to exposure on an average Los Angeles day. Direct evidence for DEP-enhanced local production of IgE was that challenge increased the number of IgE-secreting cells in lavage fluid from < 1 in 2,000,000 to > 1 in 100,000 but did not alter the number of IgA-secreting cells. There was a concomitant increase in epsilon mRNA production in the lavage cells. Additionally, DEP altered the relative amounts of five different epsilon mRNAs generated by alternative splicing, mRNAs that code for different IgE proteins. These results show that DEP exposure in vivo causes both quantitative and qualitative changes in local IgE production. The implication is that natural exposure to DEP may result in increased expression of respiratory allergic disease.
The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. It was reported that the nasal skin temperature after intranasal administration of histamine or grass pollen rose. In patients with AR, the levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) have increased in nasal fluids and mucosa.
The present study were to determine the temperature changes of the nose in rat allergic rhinitis model, and if olopatadine, an antiallergic agent with histamine H1 receptor antagonistic action, proved to be effective, were studied the productions of NGF and VEGF in nasal lavage fluids (NALF). In the present study, we used ovalbumin (OVA)-sensitized rats as an animal model of nasal allergy and examined the effects of olopatadine on the skin temperature of the nose area, and the productions of NGF and VEGF in NALF.
The temperature changes of the nose area were carried out with thermo tracer in rat passively sensitized with OVA antiserum. The numbers of sneezing episodes were counted and, NGF and VEGF levels in NALF were examined using the specific ELISA.
In OVA-sensitized rats, the number of sneezing episodes increase and the nasal skin temperature rise were provoked after OVA challenge. The levels of NGF and VEGF in NALF also were increased. Olopatadine reduced the increased frequency of sneezing and the nasal skin temperature rise. It also inhibited the increased NGF and VEGF productions in NALF.
The nasal skin temperature after OVA challenge rose even in OVA-sensitized rats. These results suggest that the suppression of the increased NGF and VEGF levels might partially be involved in the improvement of allergy-like behavior (sneezing and nasal skin temperature rise) by the treatment of olopatadine.
Olopatadine; Antihistamine; Animal model; Rhinitis; Thermography