Rolf Haye

Experimentally Induced Recruitment of Plasmacytoid (CD123high) Dendritic Cells in Human Nasal Allergy

Recent evidence suggests that the previously enigmatic cell type designated plasmacytoid monocytes can function as dendritic cells and contribute substantially to both innate and adaptive immunity. This cell type has previously been described only in bone marrow, blood, and organized lymphoid tissue, but not at effector sites with direct Ag exposure such as the mucosae. Plasmacytoid dendritic cells (P-DCs) matured in vitro can induce T cells to produce allergy-promoting Th2 cytokines; therefore, their possible occurrence in nasal mucosa during experimentally elicited allergic rhinitis was examined. Patients with silent nasal allergy were challenged topically with relevant allergen daily for 7 days. Biopsy specimens as well as blood samples were obtained before and during such provocation, and P-DCs were identified by their high expression of CD123 (IL-3R α-chain), together with CD45RA. Our results showed that P-DCs were present in low and variable numbers in normal nasal mucosa but increased dramatically during the allergic reaction. This accumulation concurred with the expression of the L-selectin ligand peripheral lymph node addressin on the mucosal vascular endothelium. The latter observation was particularly interesting in view of the high levels of L-selectin on circulating P-DC precursors and of previous reports suggesting that these cells can enter organized lymphoid tissue via high endothelial venules (which express peripheral lymph node addressin constitutively). Together, our findings suggested that P-DCs are involved in the triggering of airway allergy and that they are directed to allergic lesions by adhesion molecules that normally mediate leukocyte extravasation in organized lymphoid tissue.

The effect of cetirizine on symptoms and signs of nasal polyposis.

Forty-five patients with residual or recurrent nasal polyposis after ethmoidectomy were treated with either cetirizine at twice the daily recommended (20 mg) dose or placebo for three months. The number and size of polyps remained unchanged during the study period. Cetirizine was found to reduce nasal sneezing and rhinorrhoea effectively. The drug also had a beneficial effect on nasal obstruction in the latter part of the study. The side effects of 20 mg (double the recommended daily adult dose) of cetirizine were few and comparable to placebo.

Nasal septal perforation 1981–2005: Changes in etiology, gender and size

BackgroundSeptal perforation is an uncommon but very bothersome illness and treatment is difficult particularly with large perforations. We wanted to establish the etiology and size of nasal septal perforations in an attempt to implement preventive measures.MethodsThis is an open, prospective clinical study of patients seen at our hospital from 1981 to 2005. The clinical data of size, gender and etiology have been recorded consecutively.ResultsOne hundred and ninety seven patients (100 male, 97 female) were evaluated. Between 1981 and 1995 nasal septal perforation was caused by surgery in 40 of 102 (39.2 %). In the period 1995 to and inclusive of 2005 this percentage decreased as septal resection has been replaced by septo/septorhinoplasty. The latter was the cause for septal perforation in 14.7% in the last period. Nasal steroid and decongestive sprays have emerged as an important cause (28.4 %) during the last ten years particularly in females. In the first period 44 (43.1 %) and in the last 53 (55.7 %) patients were females. There was a noticeable reduction in the number of septal perforations 15 mm or larger in the last period.ConclusionNasal steroid and decongestive sprays are now important causes for septal perforation. Information about this complication should be given with an advice to immediately report increasing and bothersome crusting and bleeding. Warning of the simultaneous use of nasal steroid and decongestive sprays should be addressed particularly to females. All patients with symptoms of septal perforation should promptly be referred to otolaryngologists for treatment.

Vascular reactions to horseradish peroxidase in the guinea pig.

SummaryAlbino guinea pigs were given intradermal injections of the protein tracer horseradish peroxidase. In a 0.1 mM concentration the tracer did not increase vascular permeability to Evans blue-labelled plasma proteins. In a 1 mM concentration, however, the peroxidase induced a local vascular leakage. This leakage was almost totally inhibited by pretreating the animals with acetylsalicylic acid, while antihistamine had only a weak inhibitory effect. We therefore believe that prostaglandins are important mediators in this HRP-induced vascular reaction.

Morning versus evening dosing of desloratadine in seasonal allergic rhinitis: a randomized controlled study [ISRCTN23032971].

BackgroundA circadian rhythm of symptoms has been reported in allergic rhinitis and some studies have shown the dosing time of antihistamines to be of importance for optimizing symptom relief in this disease. The objective of this study was to examine the efficacy of morning vs. evening dosing of the antihistamine desloratadine at different time points during the day.MethodsPatients ≥ 18 years, with seasonal allergic rhinitis received desloratadine 5 mg orally once daily in the morning (AM-group) or evening (PM-group) for two weeks. Rhinorrhea, nasal congestion, sneezing and eye symptoms were scored morning and evening. Wilcoxon rank sum and 2-way ANOVA test were used.ResultsSix-hundred and sixty-three patients were randomized; 336 in the AM-group; 327 in the PM-group. No statistically significant differences were seen between the AM and PM group at any time points. In the sub-groups with higher morning or evening total symptom score no difference in treatment efficacy was seen whether the dose was taken 12 or 24 hours before the higher score time. There was a circadian variation in baseline total symptom score; highest during daytime and lowest at night. The circadian variation in symptoms was reduced during treatment. This reduction was highest for daytime symptoms.ConclusionsA circadian rhythm was seen for most symptoms being more pronounced during daytime. This was less apparent after treatment with desloratadine. No statistically significant difference in efficacy was seen whether desloratadine was given in the morning or in the evening. This gives the patients more flexibility in choosing dosing time.

Resorption of horseradish peroxidase from the middle ear cavity of guinea pigs

SummaryHorseradish peroxidase was injected into the middle ear and bulla of guinea pigs. In less than 5 minutes the peroxidase had reached the basement membrane, mainly through the epithelial intercellular spaces, and after 20 minutes it was observed in the lamina propria.

The epithelium of the middle ear in the guinea pig

SummaryAn electron microscopic study of aldehyde and osmium fixed normal guinea pig middle ear epithelium was made. Numerous branching microvilli occur between the cilia of the ciliated cells. The granules of the secretory cells are always surrounded by a membrane, and they vary in their content of electron dense substance. Half desmosomes are frequent in basal cells. The squamous epithelial cells of the bulla contain few microvilli and pinocytoric invaginations. In the basal part of the squamous epithelium dilations of the intercellular clefts often occur. The luminal part of the intercellular clefts are closed by multiple tight junctions.

Evaluation of the Nasal Surgical Questionnaire for Monitoring Results of Septoplasty.

Monitoring the results of surgery is important. The otorhinolaryngology department of our hospital currently uses preoperative and postoperative versions of the Nasal Surgical Questionnaire (NSQ) for continuous evaluation of nasal septoplasty. In this study, 55 patients undergoing septoplasty answered the preoperative version twice to assess the NSQs test-retest precision, and 75 patients answered the preoperative questionnaire before and the postoperative one 6 months after surgery to evaluate the NSQs ability to detect change in symptoms following surgery. Both the pre- and postoperative versions of the NSQ use separate visual analogue scales (VAS) to assess nasal obstruction during the day, at night, and during exercise. Other nasal symptoms are graded as secondary outcomes using 4-point Likert scales. The mean VAS scores for the two preoperative obstruction ratings were not significantly different. The scores were significantly higher than in a normal population. There were also significant differences between preoperative and postoperative ratings. The mean pre- and postoperative scores at night for those who reported complete improvement were 66.1 and 8.4, substantial improvement 74.5 and 24.2, and no improvement 83.3 and 76.4. The NSQ reliably assesses nasal symptoms in patients and may be useful for both short and long term prospective studies of septoplasty.

The capillaries of the middle ear mucosa in the guinea pig

SummaryThe middle ear capillaries of the guinea pig have fenestrated endothelium, and the intercellular clefts are closed by tight junctions. Intracardially injected horseradish peroxidase penetrates the fenestrae of the endothelium and gains access to the extra-cellular space beneath the epithelium, and the intercellular clefts of the epithelium.

Insect sting allergy. A study from 1980 to 2003 of patients who started treatment with venom immunotherapy between 1980 and 1998

BackgroundPreviously we treated patients with insect sting allergy with venom immunotherapy (IT) using whole body insect extracts. From 1980 we changed to insect venoms. The purpose of this study was to analyse data from the patients in order to improve our treatment.MethodsThis is an open, single centre study on patients treated with venom IT 14 years or older with a history of a systemic allergic reaction to an insect sting, a positive skin prick test (SPT) or a positive RAST and willingness to comply with five years of IT. Clinical and laboratory data were registered prospectively at the start of IT and after five years of treatment until 2003 on patients who started IT between 1980 and 1998. Questionnaires were answered in 1989, 1993 and 2003. Statistical analysis was done with Pearsons chi square, Fishers exact or the t-test.ResultsOf 315 patients treated, 44 were given bee, 248 common wasp and 23 both venoms. Of the common wasp sting incidents 5.5 % resulted in a severe allergic reaction (SAR) during adequate IT and 22% after cessation. Seventy-one per cent of the patients carried epinephrine. Precautionary steps were taken by 77% of the patients during or after inadequate IT. On or after adequate IT 83% felt completely or substantially safe. Surprisingly 29 % of those inadequately treated felt safer and 50% were satisfied with having had the opportunity to be treated. The SPT became negative in 68% of the wasp allergic patients after five years of adequate IT. Increased risk of experiencing SAR to a future sting in wasp allergic patients after cessation of adequate IT was significantly associated with a SAR due to IT during the rush regimen. SAR due to IT occurred very rarely during maintenance dosing.ConclusionAdequate venom IT is very effective while ongoing but somewhat less effective after cessation, while inadequate treatment gives poor results. More of our patients should complete five years of IT and some should continue IT. The type of reaction to IT during incremental dosing may be of help in deciding who should continue beyond five years. Maintenance IT may be taken over by the general physician.