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Notes: Langerhans cells (LC) are very potent antigen-presenting cells. In atopic disorders such as allergic rhinitis and atopic dermatitis LC are known to bear IgE surface molecules. IgE-positive LC can bind allergen and present it to T lymphocytes to induce an allergen-specific T-cell response and IgE synthesis. Therefore, IgE-bearing LC might play an important role in the triggering of the immune system to maintain ongoing IgE synthesis. The importance of the IgE-bearing LC in atopy has not been assessed but deserves further investigation to find out more about the part played by these cells, not only in the atopic disorders described here but also in others such as gastrointestinal allergy and allergic asthma.

Notes: Background Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials.Objective This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS.Patients and methods The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 μg b.i.d., FPANS 800 μg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS.Results A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery.Conclusion This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.

Notes: Background Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma.Objective The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma.Methods Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system.Results In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P 〈 0.05) and controls (P ≤ 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P 〈 0.05) and controls (P 〈 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P 〈 0.001), but also in atopics without asthma and rhinitis (P = 0.02).Conclusions This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.

Notes: Allergic sensitization of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa is the adenoid.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectivesThe objective of this study was to find evidence for our hypothesis that allergic sensitization can occur in the adenoid. Of special interest, in this context are cell types involved in antigen-allergen presentation (e.g. Langerhans cells) and effector cells of allergic disease.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsIn this study cellular infiltrates in adenoids of 16 allergic patients and 16 age-and gender-matched controls were evaluated. The number of cells positive for CD1a, CD4, CD8, CD-68, chymase, tryptase, IgE, MBP and cells positive for interleukin (IL)-4 were determined using immunohistochemical staining techniques. The epithelium, follicles and the interfollicular spaces were evaluated separately.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsWhen comparing the two groups a significant increase in cells positive for CD1a was found in interfollicular spaces of the allergic group (P = 0.008). CD1a+ cells in the follicular space and eosinophils in the interfollicular space showed a trend to be more numerous in the allergic group (P = 0.02 and P = 0.05, respectively). The other cell types investigated did not show significant differences between the groups.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionsThe results of this study show for the first time that cells involved in allergic sensitization and allergic disease differ in the adenoid of allergic children compared with controls. These findings support our hypothesis that allergic sensitization takes place in the adenoid. Furthermore, this study confirms that CD1a+ (Langerhans) cells are involved in allergic disease.

Notes: 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 Langcrhans 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 (CDla-Langerhans cells). Ki-M6 (CD68 macrophages), L25 (dendritic cells), anti-IgE, HLA-DR and HLA-DQ (Major Histoeompatibihty Complex Class II - antigen presenting eells), 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.

Notes: 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.This study can explain the seemingly conflicting reports in the literature on mast cell dynamics and degranulation and shows that the reported differences are due to differences in the techniques used and the time of evaluation.

Notes: Background Epidemiological studies in the past have focused on meteorological conditions, pollution and pollen and their relationship with symptoms of bronchial hyper-reactivity, however, there are no epidemiological studies which examine a wide range of such factors and determine their role in nasal hyper-reactivity.Objective To investigate whether environmental factors can influence symptomatology in non-allergic non-infectious perennial rhinitis (NANIPER) patients, who suffer primarily from nasal hyper-reactivity symptoms.Methods We studied 16 non-smoking NANIPER patients and seven non-smoking controls during a 218-day study period (March–October) by means of daily symptom scores and visual analogue scales for the subsets patency, secretions and sneezing, and compared them to seven primary factors which affected ‘symptoms’ and 10 secondary factors which affected primary factors only.Results The mean symptom scores in the NANIPER and control groups were 2.17 and 0.13, respectively. In NANIPER, the highest correlations of primary factors with symptomatology were found for symptom scores and sneezing with minimum daytime temperature (r = −0.62 and −0.45, respectively), ozone and NO concentrations. Patency and secretions were associated with minimum daytime temperature (r = −0.39 and 0.32, respectively). Time series analysis, however, correcting for several confounders such as autocorrelated symptomatology, showed that minimum daytime temperature and daytime relative humidity made an independent contribution to symptoms. In the control group, correlations were much lower, though present. Time series analysis was not possible.Conclusions We conclude that in a mild climate with relatively low levels of pollution, minor pollution and meteorological disturbances result in substantial changes in nasal reactivity symptoms in NANIPER patients, but not controls, irrespective of other factors such as allergy or infection.

Notes: The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.〈section xml:id="abs1-2"〉〈title type="main"〉MethodsThis single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ, RANTES and TNFα) were counted in the biopsies.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsPreventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL-5 and IL-6. After allergen provocation, levels of most of the measured cytokines (IL-3, IL-5, IL-6, IL-13, IFNγ, RANTES and TNFα) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL-3, IL-6 and IL-8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL-3, IL-10 and IL-13).〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionThese results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.

Notes: To compare the safety and efficacy of fluticasone propionate aqueous nasal spray (FPANS) and oral ketotifen in children aged 2–4 years with perennial rhinitis. A randomized, multicentre, double-blind, double dummy, placebo-controlled study. Paediatric patients between the ages of 2–4 years with perennial rhinitis. Rhinitis symptoms score (parent-rated), clinical evaluation of symptoms (investigator-rated) and adverse event profiles during the treatment period. Patients treated with FPANS had a significant reduction in both the total night-time rhinitis symptom assessment for weeks 4–6 (p-value 0.036), and the total daytime rhinitis symptom score over the same period (p-value 0.049). Generally, except for nasal itching/rubbing over weeks 1–3, the patients taking FPANS had lower recorded symptom scores for all individual symptoms measured. Nasal blockage, in particular, was significantly reduced over the 4–6 week period (p-value 0.027). The overall investigator-rated clinical evaluation showed substantial improvement or improvement in nine of 12 of the children taking FPANS compared with four of 14 taking ketotifen. Finally, there were no reports of serious adverse events, the incidence of drug-related adverse events was low and there was no statistical difference between the groups. FPANS may be an appropriate treatment to control the symptoms of rhinitis in children between 2 and 4 years old.