Long-term effects of corticosteroid nasal spray on nasal inflammatory cells in patients with perennial allergic rhinitis.

BACKGROUND: The effect of long-term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear. OBJECTIVES: To investigate the long-term effect of fluticasone propionate aqueous nasal spray (FPANS) on nasal mucosal inflammatory cells and efficacy in a 1-year study in patients with perennial allergic rhinitis. METHODS: In a 1-year, double-blind, placebo-controlled study of duration we investigated the influence of a topical corticosteroid (FPANS), on Langerhans' cells (CD1a+ cells), T cells, mast cells, eosinophils and macrophages in nasal mucosa in 42 patients with perennial allergic rhinitis. Efficacy was evaluated by nasal symptom score. RESULTS: The FPANS group experienced significantly less sneezing and nasal itching compared with the placebo group. The total symptom score in the FPANS group declined significantly in comparison with baseline (P = 0.007) and placebo group (P = 0.009). After 1 year of active treatment, a significant decrease was seen in the epithelium in numbers of Langerhans' cells, CD3+, CD4+, CD8+ cells, mast cells and eosinophils. In the lamina propria, there was a significant decrease in eosinophils. CONCLUSION: These findings show that FPANS treatment results in a decrease of nasal inflammatory cells. Furthermore, the efficacy of FPANS improves after prolonged treatment.

A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safety and biopsy study.

In a 1-year, placebo-controlled, double-blind, randomized study the long-term effect of Fluticasone Propionate Aqueous Nasal Spray (FPANS) in 42 patients with a perennial allergic rhinitis was studied with regard to safety and efficacy. Twenty-nine patients completed the entire treatment period. After 1 year of treatment no deleterious changes consequent on therapy were observed in nasal mucosal biopsies. The appearance of the epithelial layer, the degree of cellular infiltration, the extent to which the sinusoids were dilated and the degree of tissue oedema improved or remained unchanged in 93% of the patients of the FPANS group, versus 75% of the placebo group, and worsened in 7% of the FPANS group versus 25% of the placebo group. Assessment of the changes in haematological, biochemical, urinary, plasma cortisol levels, and in the findings during nasal examination revealed no significant differences between the two treatment groups. After 1 year of treatment symptom scores for sneezing, nasal itching, and total symptom score were significantly better in the FPANS treated group (P < 0.05, P < 0.05, P < 0.01). An initial reduction in total symptom score was found after 4 weeks FPANS treatment with a further reduction after 8 months of FPANS treatment. These findings suggest that the maximum efficacy of topical intranasal steroids is reached after long-term treatment, and thus advocates longer usage before treatment is stopped because of presumed inefficacy.

Local corticosteroid treatment: the effect on cells and cytokines in nasal allergic inflammation.

Regular and prophylactic use of topical corticosteroids is a well tolerated and effective treatment for allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of infiltrating inflammatory cells, releasing mediators, and cytokines. Corticosteroids can suppress many stages of the allergic inflammatory process. This may explain their potent effect on allergic symptomatology. The reduction in cell numbers and probably also cytokines by local corticosteroid therapy differs from cell to cell. Some cells, such as antigen presenting (Langerhans) cells and eosinophils, are highly sensitive to corticosteroid treatment. Others, like T cells, are only significantly reduced in exaggerated situations, for instance after provocation with a high allergen dose or after treatment with a high dose of corticosteroids. Some cells, like macrophages, are not influenced at all.

Allergen binding to specific IgE in the nasal mucosa of allergic patients.

BACKGROUND: Until now, it has not been possible to identify specific IgE locally in the airway mucosa. In this study we investigated the possibility of determining specific allergen binding locally in the nasal mucosa. METHODS: Nasal mucosal biopsy specimens were taken from 11 patients with symptoms of an isolated grass pollen allergy, 10 patients with symptoms of perennial allergic rhinitis in response to house dust mite allergen, and 10 nonallergic control subjects. Sections of these biopsy specimens were stained by using commercially available biotinylated allergens (AlaSTAT, Diagnostic Products Corp.). RESULTS: Staining with biotinylated grass pollen (GP1) demonstrated positive cells only in patients with grass pollen allergy. Biotinylated Dermatophagoides pteronyssinus (D1) only stained cells in patients with perennial allergy. Specific binding of allergen to cells of patients with allergy and the blocking experiments proved the method to be highly specific. Allergen-positive cells stained double with IgE, the high-affinity receptor for IgE (Fc epsilon RI), CD1, HLA-DR, tryptase, and chymase. Most allergen-positive cells proved to be mast cells. CONCLUSION: This immunohistochemical study shows the presence of specific IgE against grass pollen and house dust mite allergens locally on cells in the airway mucosa.

Allergic rhinitis and inflammation: the effect of nasal corticosteroid therapy.

Topical corticosteroids have proved to be effective in the treatment of allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of inflammatory cells and cytokine release and hence the efficacy of corticosteroids is associated with their anti-inflammatory action. New advances in allergic inflammation now suggest that not only mast cells and eosinophils but also T-lymphocytes and antigen-presenting dendritic cells, play an important role in the inflammatory reaction. The effect of topical fluticasone propionate on cellular infiltration in the nasal mucosa is examined, with an emphasis on two studies performed in Rotterdam, The Netherlands. The cells influenced most by corticosteroid therapy were Langerhans' cells (antigen-presenting cells), which were almost completely eradicated, possibly resulting in diminished antigen presentation, and eosinophils. There was a reduction in the number of epithelial mast cells, but the number of T-lymphocytes only decreased following high doses of corticosteroid therapy or long-term treatment. However, T-lymphocyte function was influenced, as shown by the reduction in the T-helper2 (TH2)-related cytokines, interleukin (IL)-4 and IL-5. Topical corticosteroid therapy had no effect on the accumulation of macrophages. The reduction in antigen presentation, and the decrease in T-lymphocyte stimulation and cytokine production, may cause a reduced influx of eosinophils and other inflammatory cells, resulting in diminished symptomatology.

The effect of nasal steroid aqueous spray on nasal complaint scores and cellular infiltrates in the nasal mucosa of patients with nonallergic, noninfectious perennial rhinitis.

Topical corticosteroids are the therapy of choice for nonallergic, noninfectious perennial rhinitis (NANIPER). However, the efficacy of steroid therapy in NANIPER is controversial, as is its mode of action. To our surprise, of 300 patients initially diagnosed as having NANIPER, only 65 reached threshold nasal symptom scores. Patients were randomized into four different treatment regimens: placebo administered twice daily (BD) for 8 weeks, fluticasone propionate aqueous nasal spray (FPANS) (200 microg) once daily (OD) and placebo OD for 8 weeks, FPANS (200 microg) OD and placebo OD for 4 weeks followed by FPANS (200 microg) BD for 4 weeks, and FPANS (200 microg) BD for 8 weeks. A small decrease in nasal symptoms was found, which only reached significance for sneezing in the FPANS 200 microg BD group. A significant dose-dependent decrease in immunocompetent cells was found in nasal biopsy specimens obtained before, after 4 weeks, and after 8 weeks of treatment. We conclude that FPANS did not significantly reduce nasal symptoms in this group of selected NANIPER patients, even though a significant effect on cells in the nasal mucosa was seen.

Fixation with Carnoy's fluid reduces the number of chymase-positive mast cells: not all chymase-positive mast cells are also positive for tryptase.

Mast cells in the nasal mucosa can be studied by means of monoclonal antibodies (mAb) against tryptase (T+MC) and chymase (C+MC). Fixation with acetone gives more positive cells than does fixation with Carnoy's fluid. In frozen biopsy specimens of allergic nasal mucosa fixed with acetone, the number of T+MC equals that of C+MC. When fixed with Carnoy's fluid, however, the number of T+MC is larger than the number of C+MC. The decrease in both T+MC and C+MC resulting from fixation with Carnoy's fluid is time-related and depends on the type of mAb used. Carnoy fixation time gives a decrease in the number of C+MC within 1 min, whereas the number of T+MC decreases only after 10 min. Within 1 min, the number of C+MC decreases to a level where continued fixation no longer gives further decreases in the number of cells. Two populations of mast cells can be distinguished here: one sensitive and the other insensitive to Carnoy's fluid. When double-staining is used, fixation with acetone gives three populations of mast cells: one positive for tryptase (T+C-MC), another positive for tryptase and chymase (T+C+MC), and a third one positive for chymase (T-C+MC). These three populations were found in lymph node, spleen, thymus, dermis, lung parenchyma, small intestinal submucosa, and nasal mucosa.

Antigen presenting cells in the nasal mucosa of patients with allergic rhinitis during allergen provocation.

BACKGROUND: The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis. OBJECTIVES: The aim of the study was to investigate the presence and dynamics of APC with special emphasis on Langerhans cells (LC) in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season. METHODS: Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with allergen during a 2-week period in the winter. Biopsy specimens were obtained once before, six times during and once after the provocation period. Biopsy sections were stained with monoclonal antibodies: OKT6 (CD1a-Langerhans cells), Ki-M6 (CD68-macrophages), L25 (dendritic cells), anti-IgE, HLA-DR and HLA-DQ (Major Histocompatibility Complex Class II-antigen presenting cells), as well as staining with acid phosphatase. RESULTS: APC with different characteristics are present in the epithelium and lamina propria of the nasal mucosa. The number of LC increased significantly in epithelium and lamina propria. IgE(+)-LC were present in the nasal mucosa and increase during provocation. HLA-DR+ cells with dendritic and lymphocytic morphology and HLA-DQ+ cells were found. The number of these cells increased during provocation in epithelium and lamina propria. The number of HLA-DR+ epithelial cells did not change. A significant increase in the number of Ki-M6+ cells (macrophages) was found in the lamina propria. However, Ki-M6+ cells increased to the same extent in the lamina propria in the control group. CONCLUSION: APC are influenced by allergen provocation. This study supports the hypothesis that (IgE+) LC are involved in allergic rhinitis. The role macrophages play remains doubtful.

Dynamics of nasal eosinophils in response to a nonnatural allergen challenge in patients with allergic rhinitis and control subjects: a biopsy and brush study.

BACKGROUND: Eosinophils are thought to play an important role in the symptomatology and pathophysiology of allergic rhinitis. Most quantitative studies on eosinophils in nasal mucosa have focused on the dynamics of eosinophils in the acute and late phases of the allergic reaction by using different cell sampling techniques. Little is known about the dynamics of eosinophils during a more prolonged period of allergen exposure and the activation of eosinophils induced by allergen challenge. OBJECTIVE: The aim of this study was to investigate the dynamics and activation of the eosinophils in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season. METHODS: Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with the allergen during a 2-week period in the winter. Nasal brush specimens were obtained before provocation and each day during the provocation period. Biopsy specimens were obtained once before, six times during, and once after the provocation period. Preparations made of nasal brush and nasal biopsy specimens were stained with the monoclonal antibody BMK 13 and Giemsa stain as paneosinophil markers and with the monoclonal antibody EG2 to identify activated eosinophils. RESULTS: We found significant increases in the total number of eosinophils and the number of activated eosinophils in the epithelium and lamina propria. These increases were most explicit in the second week. BMK 13 was found to be a paneosinophil marker superior to Giemsa staining. CONCLUSION: Eosinophils are not only involved in the acute and late phases of the allergic reaction but are probably even more involved in the chronic phase.

Effect of 3 months' nasal steroid therapy on nasal T cells and Langerhans cells in patients suffering from allergic rhinitis.

The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double-blind, placebo-controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a+ cells), HLA-DR+ cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CD1a+ cells and HLA-DR+ cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.

The effect of fluticasone propionate aqueous nasal spray on nasal mucosal inflammation in perennial allergic rhinitis.

Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans' cells and T-cells play an important role. Langerhans' cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T-cells by the IgE-positive Langerhans' cells. The T-cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T-cells is not usually influenced by corticosteroid treatment; however, the function of the T-cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans' cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T-cell stimulation may result in a reduction of the reactions that are dependent on T-cell-derived mediators.

Mast cells, eosinophils and IgE-positive cells in the nasal mucosa of patients with vasomotor rhinitis. An immunohistochemical study.

Vasomotor rhinitis (VMR) is a disorder of unknown pathogenesis. Forty patients with VMR were carefully selected on the basis of inclusion and exclusion criteria proposed by Mygind and Weeke. Nasal biopsy specimens were taken in the patient group as well as in a group of ten controls. Brush cytology was also taken in the VMR group. Inflammatory cells were identified and counted in the nasal mucosa, with the use of immunohistochemical techniques and a panel of monoclonal antibodies. Eosinophils were studied with the use of BMK13, EG2, and Giemsa. Mast cells were studied with anti-chymase (B7), anti-tryptase (G3) and toluidine blue. Sections were stained with IgE as well. There was no significant difference in the number of eosinophils, mast cells and IgE-positive cells between the two groups. Additionally, in contrast with other reports, in sections that were double-stained with anti-chymase and anti-tryptase, single chymase-positive cells were found.

Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non-allergic controls: a biopsy study.

Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti-IgE and toluidine blue staining of biopsy specimens. In allergic patients anti-IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated. The study was composed of two parts done in different patient groups. In the first part of the study biopsies were performed in 23 patients with isolated grass-pollen allergy, once during natural provocation in the summer and once in the winter. Biopsies were also performed in 12 controls. Non-allergic controls were found to have the same number of mast cells in the lamina propria as asymptomatic allergic patients. The controls seldom have mast cells in the epithelium. The patients with isolated grass-pollen allergy showed an increase in the numbers of mast cells in the lamina propria during natural provocation and the same seemed to occur in the epithelium as well. During natural provocation almost all of the mast cells in the epithelium and half of those in the lamina propria were degranulated. In the second part of the study 17 patients with isolated grass-pollen allergy and four controls were challenged daily with allergen extract during a 2-week period in the winter. During this period biopsies were performed at eight different occasions, i.e. once before, six occasions during and once after the provocation period. The results of this part of the study showed that during provocation mast cells migrate to the surface of the nasal mucosa, where they become degranulated, and that the pool of mast cells in the lamina propria was apparently replenished by migration of mast cells from the vessels in the lamina propria. The total number of mast cells in the lamina propria remained approximately the same while the mast cells residing in an increasingly thick layer measured from the basal membrane into the lamina propria became degranulated. After 2 weeks, 82% of the mast cells in the lamina propria was degranulated and it was only in the deepest layers that some toluidine blue positive cells were found.(ABSTRACT TRUNCATED AT 400 WORDS)