The pathogenesis of allergic rhinitis : cellular aspects with special emphasis on Langerhans cells

Present ideas concerning the pathogenesis of allergic rhinitis are largely deduced from systemic investigations and extrapolated from studies in the skin and the lung. Studies on allergic rhinitis generally comprise clinical aspects and/or biochemical, humoral and cellular features of the epithelial surface and the nasal secretions. little is known about what happens in the nasal mucosa itself. The aim of the investigations, described in this thesis, was to investigate the cellular aspects of the pathogenesis of allergic rhinitis using immunohistochemical staining techniques in biopsy specimens of nasal mucosa. A biopsy method was developed, which can be repeated several times (chapter 4). Biopsy specimens of nasal mucosa of patients with allergic rhinitis and nonallergic controls were studied to broadly characterize and quantitate the cellular infiltrates (chapter 5 and 7). Mast cell dynamics and degranulation were studied in an allergen provocation study out of the grass-pollen season (chapter 6). Although mast cell degranulation has long time been considered to be the proper model to explain allergic rhinitis, the findings described in the first part of this thesis, suggest that other cell types, particularly antigen presenting cells and T cells, are involved as well. The antigen presenting cells were further characterized and their contact with other cell types was evaluated (chapter 8). The dynamics and the behaviour of these cells in the nasal mucosa of patients with isolated grass-pollen allergy were studied in biopsy specimens taken before, during and after natural provocation (chapter 9) and during allergen provocation studies outside the grass-pollen season (chapter 1 0 and 11). Finally the effect of treatment with the nasal corticosteroid spray Fluticasone on antigen-presenting cells, and especially the langerhans cell was studied (chapter 12)

Differences in nasal cellular infiltrates between allergic children and age-matched controls

Little is known about the cellular infiltrates in the nasal mucosa of children. This study was set up to compare the nasal cellular infiltrates in biopsy specimens from allergic children and controls. Atopic children were distinguished from controls on the basis of symptoms of allergic rhinitis and/or asthma, total serum immunoglobulin (Ig)E, family history and specific serum IgE to food and aeroallergens. Fifteen allergic patients (median age 4.3 yrs) and 15 age-matched nonallergic control subjects were evaluated. The number of cells positive for CD1a, CD4, CD8, CD19, CD68, chymase, tryptase, IgE and major basic protein was determined in the mucosa of the inferior turbinate. A significantly higher number of IgE-positive cells and mast cells was found in the epithelia of the allergic group. In the lamina propria, higher numbers of IgE-positive cells and eosinophils were found. Langerhans' cells positive for IgE were only seen in allergic children with specific serum IgE against aeroallergens. These children also had a higher number of IgE-positive mast cells compared to controls and atopic children without specific serum IgE. These results show that the nasal cellular infiltrates of allergic children differ from nonallergic control subjects. Prior to the detection of specific serum immunoglobulin E, cellular changes can be found in the nasal mucosa of atopic children

Intranasal cold dry air is superior to histamine challenge in determining the presence and degree of nasal hyperreactivity in nonallergic noninfectious perennial rhinitis

The objective of the study was to compare cold dry air (CDA) and histamine in differentiating patients with nonallergic noninfectious perennial rhinitis (NANIPER) from control subjects. Nasal reactivity (nasal patency, mucus production, and sneezing) in 16 symptomatic nonsmoking patients with NANIPER and seven nonsmoking control subjects was measured with standardized CDA and histamine provocation series in a randomized crossover study. Intranasal CDA resulted in increased mucus production and nasal blockage in a dose-dependent manner in patients with NANIPER but not in control subjects. Sneezing did not occur. The reproducibility of CDA for patency and mucus production was good. Sen

Quality of life and costs of Filgrastim® (G-CSF) treatment in patients with persistent chronic rhinosinusitis

This is the first report of the double blind randomized clinical trial, in which we investigated the influence of Filgrastim(r) on the quality of life and treatment costs of chronic sinusitis patients who did not respond to regular treatments. The quality of life of 56 patients was assessed 5 times during the 24-week trial with the EuroQol, the SF-36 and the McGill Pain questionnaire. We further controlled for "responsiveness", based on clinical impression. Direct medical and indirect non-medical costs per patient during the trial were analyzed, based on data from clinical record forms and the hospital information system. We further compared the direct medical costs to the costs of regular treatment. The quality of life scores were all below population norm scores. Quality of life scores of the Filgrastim(r) group suggested a better quality of life than the placebo group, although none of the differences were statistically significant. There were indications that controlling for responsiveness increased the power of the design. The difference in costs between the trial groups were driven by the Filgrastim(r) costs (Euro 4899). When Filgrastim(r) costs were neglected, no difference in costs remained. Except for Filgrastim(r), total direct costs summed up to Euro 2712 and the indirect costs to Euro 582. Total direct costs of a 24-week regular treatment were three times lower than the costs of the trial treatment. While significantly increasing treatment costs, Filgrastim(r) administration does not lead to a better quality of life of chronic sinusitis patients, although there were

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 see

Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients

Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T(0)) and 24 h (T(24)) after SBP. Nasal biopsies were obtained at T(0), 1 h after SBP (T(1)), and T(24). Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p = 0.03) of atopic subjects at T(24). We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epitheliu

Mast cells, eosinophils and IgE-positive cells in the nasal mucose 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

Why Rudolph's nose is red: Observational study

Objective: To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus's sleigh, is due to the presence of a highly dense and rich nasal microcirculation. Design: Observational study. Setting: Tromsø, Norway (near the North Pole), and Amsterdam, the Netherlands. Participants: Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. Main outcome measures: Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. Results: Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers' nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm2. Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. Conclusions: The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph's legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer's brain, factors essential for flying reindeer pulling Santa Claus's sleigh under extreme temperatures