Mono-allergic and poly-allergic rhinitis patients have comparable numbers of mucosal Foxp3+CD4+ T lymphocytes.

BACKGROUND: We previously found that allergic rhinitis patients with an isolated pollen sensitization responded more strongly to a nasal provocation with grass pollen (GP) than patients who had an additional house dust mite (HDM) sensitization. To elucidate this phenomenon, we investigated the dynamics of Foxp3+CD4+ T lymphocytes in allergic rhinitis patients with distinct allergen sensitizations. METHODS: Three groups of allergic rhinitis patients with skin prick test confirmed allergic sensitizations were investigated and compared to 14 healthy controls: 14 subjects with an isolated grass pollen sensitization (Mono-GP); 9 subjects with isolated housedust mite sensitization (Mono-HDM); 29 subjects with grass pollen and house dust mite sensitization (poly-sensitized). Subjects in the Mono-GP group were challenged with grass pollen extract, subjects in the Mono-HDM group were challenged with house dust mite extract, subjects in the poly-sensitized group and the healthy controls were randomly challenged with either grass pollen or house dust mite. Nasal biopsies were taken before and after nasal provocation. We compared the distribution of FoxP3+CD4+ cells in nasal biopsies before and after nasal provocation using immunohistochemistry. RESULTS: There was no difference in the number of FoxP3+CD4+ cells between healthy and the three allergic groups at baseline.Nasal provocation did result in an increase in eosinophils in the three allergic groups, but did not result in a change in the number of FoxP3+CD4+ cells in any of the groups or induced differences between any of the groups. CONCLUSION: Clinical differences in the response between mono-GP and multiple-sensitized allergic individuals are not related to differences in the number of regulatory T cells in the nasal mucosa.

Predictors of post-operative response to treatment: a double blind placebo controlled study in chronic rhinosinusitis patients.

BACKGROUND: In the majority of CRS patients suffering from primary or recurrent CRS, topical glucocorticoids are highly effective. A subset of CRS patients, however, does not respond to (topical) glucocorticoids and requires surgical intervention. Although surgery is highly effective in those individuals, recurrence of disease is observed in some. In this study we describe our search for one or more predictors predicting the response to surgery in combination with peri-operative oral glucocorticoids in CRS patients. METHODS: Thirty-five inferior turbinate specimens were randomly selected from a larger group of CRS patients requiring FESS for persistent disease that either responded favorably or demonstrated recurrent disease. Tissue biopsies were taken at the time of surgery and compared for inflammatory markers, endothelial cell markers, and various leukocyte subsets using immunohistochemistry. RESULTS: Compared to non-responders, the baseline level of lamina propria activated eosinophils is significantly increased in CRS patients responding to surgery in combination with peri-operative oral glucocorticoids treated or not treated post-operatively with topical glucocorticoids. No significant differences were observed for all other studied parameters. Post-operative treatment with FPANS 100 µg q.i.d. was significantly associated with response to treatment. A trend towards association was observed for increased numbers of eosinophils at baseline. CONCLUSION: Our data suggest that CRS patients with higher levels of eosinophils are less likely to suffer from post-operative recurrent sinonasal disease when treated post-operatively with FPANS 100 µg q.i.d.

Nasal endothelial interleukin-10 expression is negatively correlated with nasal symptoms after allergen provocation.

BACKGROUND: Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms. METHODS: In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores. RESULTS: At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment. CONCLUSIONS: There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms.

Topical glucocorticoids downregulate COX-1 positive cells in nasal polyps.

BACKGROUND: Influx of inflammatory cells is one of the hallmarks of nasal polyposis. As glucocorticoids (GC) are known to exhibit strong anti-inflammatory effects, these drugs are frequently used in the treatment of the disease. Part of the anti-inflammatory effects of GC is attributed to their interference with prostanoid synthesis. As cyclooxygenases (COX) are key enzymes in the synthesis of both pro- (COX-1, COX-2) and anti-inflammatory prostanoids (COX-2), we investigated the role of topical GC on COX-1, COX-2 and inflammatory markers in nasal polyps (NP). METHODS: Immunohistochemical analysis of inflammatory markers (CD68, CD117, MBP, elastase, IgE, BB-1, IL-4, IL-5 and IL-6), COX-1 and COX-2 was performed on normal nasal mucosa (NM) (n = 18), non-GC treated NP (n = 27) and topical GC treated NP (n = 12). NP groups were matched for allergy, asthma and ASA intolerance. RESULTS: Increased numbers of eosinophils, IL-5+ cells and IgE+ cells and decreased numbers of mastcells are striking features of NP inflammation (P < 0.05). In addition, increased numbers of COX-1+ cells are observed in NP epithelium compared to NM (P < 0.05). CONCLUSION: Topical GC significantly reduce the number of COX-1+ NP cells (P < 0.05), but have no significant effect on COX-2+ NP cells. No significant reduction in the number of eosinophils is observed for GC treated NP. The number of IL-5+ cells is however increased significantly upon GC treatment (P < 0.05).

Nasal epithelial cells express IL-10 at levels that negatively correlate with clinical symptoms in patients with house dust mite allergy.

BACKGROUND: Despite constant exposure to micro-organisms and other immunogenic environmental factors, relatively very few immunological responses are initiated in the nasal mucosa. Although several mechanisms could play a role in maintaining this immune suppressive milieu, none of them have been validated. Previous data from our group suggested that locally produced interleukin (IL)-10 could be involved in maintaining local homeostasis. METHODS: To investigate the role of epithelial IL-10 expression in the manifestation of allergic symptoms, we used immunohistochemistry to study the expression of IL-10 in the nasal epithelium of healthy individuals and house dust mite allergic patients. In the allergic patients, we determined potential correlations of epithelial expression with allergic symptoms, both at baseline and after allergen provocation. RESULTS: IL-10 is expressed in the basal and differentiated epithelial cells of both healthy individuals and allergic rhinitis patients. In the allergic individuals, there is a strong negative correlation at baseline between the epithelial expression level of IL-10 and rhinorrhoea and sneezing, but not between that expression level and nasal blockage or peak nasal inspiratory flow (PNIF). This correlation disappears with steroid treatment or after allergen provocation, although the expression at baseline seems to predict PNIF scores after provocation. CONCLUSIONS: Our data not only reveals IL-10 expression by human nasal epithelial cells, but also suggests that nasal epithelial IL-10 regulates allergic symptoms. Targeting the regulation mechanisms affecting IL-10 or targeting the regulation mechanism affected by IL-10 could constitute new options for the treatment of allergic disease.

Evaluation of an intranasal house dust mite provocation model as a tool in clinical research.

BACKGROUND: As a result of the all-year-round exposure to house dust mite (HDM), perennial rhinitis patients never have a clear symptom-free period. In this study, we investigated whether, despite these symptoms, we can still use nasal HDM provocations to study perennial allergic rhinitis and the effects of treatment. METHODS: In a parallel-group study, after 1 week treatment with either fluticasone propionate aqueous nasal spray (FPANS) or placebo, 20 patients, allergic to HDM, registered symptoms (nasal obstruction, rhinorrhoea, sneezing, pruritus and eye symptoms) using three different scoring methods [Lebel, categorical and visual analogue scale (VAS)] and peak nasal inspiratory flow (PNIF) after HDM provocations. Provocations were performed with 1000 biological units/ml and 24 h later with 10,000 biological units/ml of HDM. Before and after the provocations, nasal mucosa biopsies were taken for immunohistochemical staining to determine the number of eosinophils. RESULTS: House dust mite provocations resulted in an increase in symptoms and a decrease in PNIF. Even at high-dose provocation, the FPANS group registered significantly lower symptoms than the placebo group for nasal blockage, sneezing, eye symptoms, and PNIF in both early and late phases. FPANS also suppressed rhinorrhoea during the late phase and the influx of eosinophils in the lamina propria. CONCLUSION: Despite the high background of symptoms, allergic responses can be induced in this perennial rhinitis model. The VAS score seems most suited to detect these changes and the suppression of symptoms by 7 days of FPANS treatment. Epithelial eosinophilia at baseline was correlated positively with the severity of the reaction after the first provocation.