[Immunology and immunopathology of the nasal mucosa].
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Antibody Formation↗
Biomedical subjects
C Bachert
Publications and source records attributed to C Bachert.
Experimental studies on the relationship between maxillary sinus ventilation and various obstructions of the nose and nasopharynx.
The relationship of the nasal and the antral ventilation was studied with a plastinated model of a human nose. The effects of adenoidal hyperplasia and septal deviations on the antral ventilation were measured. It could be demonstrated that the aerodynamic effect of an obstruction within the nasal cavity largely depends on the localisation of the stenosis (anterior or posterior to the maxillary ostium). Additionally, the influence of an ostial obstruction on the antral ventilation was examined in dependence on the nasal ventilation. We were able to demonstrate that the antral pressure variations not only reflect the ostial function but as well the total aerodynamics of the upper respiratory tract. From this point of view we discuss diagnostic and therapeutic conclusions.
Airway Obstruction↗
Localization of IgE synthesis in immediate-type allergy of the upper respiratory tract.
The localization of allergen-specific IgE synthesis in allergic diseases of the upper respiratory tract is so far unknown. It has been suggested that the IgE production takes place in the nasal mucosa itself. The present immunohistochemical studies with anti-IgE and monoclonal markers for B lymphocytes, plasma cells, antigens of the major histocompatibility complex, T helper and T suppressor cells indicate that there are no IgE-producing plasma cells in the nasal mucosa of patients with seasonal allergic rhinitis. The IgE-associated cells have been defined as two different types of mast cells. Furthermore we found IgE-associated lymphoid follicles in palatine as well as in nasopharyngeal tonsils and in cervical lymph nodes from allergic patients. IgE-specific activated B lymphocytes and plasma cells were identified in direct contact with migratory mast cells in these lymphoid tissues. We therefore suggest that IgE synthesis takes place in the lymphoid tissues of Waldeyer's ring and in downstream cervical lymph nodes and that migratory mast cells transport specific IgE back to the nasal mucosa to mediate the allergic reaction.
B-Lymphocytes↗
[Computer-assisted rhinomanometry (CAR)].
We developed a software program for computer-aided rhinomanometry (CAR) to assess the nasal resistance curve before calculating the rhinomanometrical parameters. This program forms the basis for correct processing of data in diseases associated with nasal obstruction. We were able to demonstrate the superiority of CAR over the conventional averaging of the resistance curves in 246 measurements. Thus computer-aided rhinomanometry opens up a wide range of diagnostic possibilities.
Airway Obstruction↗
[Sensitivity and specificity of intranasal provocation].
As a result of the development of a number of modern biochemical and immunological in-vitro techniques together with in-vivo skin tests, it has been possible to purify, characterise and standardise allergen extracts for diagnosis and therapy. Despite the diagnostic value of the NPT for daily clinical practice, no standardisation has been achieved to establish the correct allergen concentration for that test. In 43 patients allergic to grass we determined the nasal threshold by means of allergen titrations with increasing concentrations from 1000 BE/ml to 170,000 BE/ml (1000 BE/ml = 1 HEP). For evaluation we used rhinomanometry and symptom scores. 10 normal subjects served as control. In order to achieve the best sensitivity and specificity of the NPT, allergen concentrations of 100,000-150,000 BE/ml had to be used. For research purposes an allergen titration is recommended as standard. Much work remains to be done in respect of technique and evaluation criteria to establish a standardised and reliable NPT.
Airway Resistance↗
[Critical remarks on chemotherapy of malignant tumors of the head and neck].
Chemotherapy of head and neck carcinomas has been the subject of 111 relevant publications reporting on more than 4,500 patients in the international literature of the past five years. Results of similar treatment protocols have been grouped together and tumour remission and survival time determined. Chemotherapy did not result in cure or increased survival times, neither alone nor in combination with irradiation nor when applied as adjuvant treatment. Inductive chemotherapy may result in producing a favourable effect on the prognosis of advanced carcinomas. The beneficial character of palliative chemotherapy is a generally accepted fact. Improvement of treatment results will be achieved only via centrally coordinated, randomised and prospective studies as well as by intensive fundamental research.
Antineoplastic Combined Chemotherapy Protocols↗
[Demonstration of IgE associated cells in atopic nasal mucosa using the immunoperoxidase method].
IgE-associated cells in the specimens of 25 allergic and non-allergic subjects were stained by the peroxidase technique with the use of a polyclonal antiserum. The technique is described and its advantages over the immunofluorescence procedures are shown. In each allergic subject IgE-associated cells could be stained, whereas no cells could be found in non-atopic subjects after suppressing non-specific background staining (Fig. 4). Therefore, this method allows to distinguish between IgE-mediated allergic diseases of the nasal mucosa and diseases of other pathomechanisms. The stained cells formed a specific distribution pattern with a typical accumulation in the subepithelial and epithelial layer (Fig. 2), whereas only few cells were found in the mucosal glands.
Eosinophils↗
[Reproducibility of the intranasal provocation test].
Perennial allergic diseases of the upper respiratory tract are becoming more and more frequent. Treatment is difficult and indicated only if there is clear evidence that the suspected allergen definitely causes the symptoms. To date the intranasal allergen provocation test (INT) is the only possibility to prove the actuality of an allergen at the shock organ (e.g. the nasal mucosa). However, the validity of the INT is diminished because the test is handled differently by various authors. In this study we therefore examined the extraseasonal reproducibility of INT in 21 patients allergic to graminaceae. After determination of an individual allergen concentration for every subject the INT was repeated five times under standardised conditions (allergen lyophilised and standardised in biological units, application of the allergen solution to the inferior concha, rhinomanometrical measurement of the nasal flow before and 15 min. after the provocation). Using a flow reduction of 30 per cent as borderline value we found a high reproducibility of the INT. The nasal reaction was not diminished after repeating the test within 24 hours. The essential and so far unsolved problem of the INT is not due to the technical device but to the concentration of the allergen solution which must correspond to the natural exposition of the patient.
Adolescent↗
[Respiratory volume flow controlled total occlusion method, a new principle for measuring bronchial resistance].
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Adolescent↗
[Experimental studies of the effect of nasal respiratory obstruction on ventilation of the maxillary sinus].
The connection between obstruction in the nasal cavity and the antral ventilation is not completely understood. To investigate this problem, experiments with a tube model and a plastinated model of a human nose have been performed (see Fig. 1). It was possible to take the septum off that model to replace it by different septal deviations or to imitate adenoidal hyperplasia. Furthermore, the antral ostium was replaced by cannules of different sizes (0.38-7.06 mm2). Thus, we were able to record the resistance of the nose, the pressure in front of the ostium and the pressure in the sinus synchronously. We were able to show that the antral pressure depends on the depth of breath and its frequency, the choanal pressure, the resistance of the total nose, the localisation of septal deviations in the cavity of the nose and the size of the ostium (see table 1). Proximal obstructions in the nasal cavity--such as adenoidal hyperplasia--caused a diminishing antral pressure amplitude during respiration, distal obstructions caused an increase of the antral pressure (see Fig. 3). Accordingly, the isthmus nasi is a physiological distal obstruction which causes an amelioration of the sinus ventilation. If the ostial surface is reduced to below 1 mm2, there is a time delay of the pressure in front of and behind (i.e. in the sinus) the ostium (see Fig. 2). This means a reduction of the antral pressure amplitude depending on the frequency of respiration.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Obstruction↗
[A special case of multiple hemangiomas in the head and neck area: a variation of the Maffucci syndrome?].
A 21-year-old patient with multiple hemangiomas in the mouth and in the skin of the neck and a simultaneous enchondromatosis in the hands is described. This congenital mesodermal dysplasia cannot be classified under known syndromes. It is named after Angelo Maffucci and is a combination of an enchondromatosis and multiple haemangiomatosis. Maffucci described this syndrome in 1881. After the presentation of the syndrome and differential diagnostic considerations of other diseases belonging to the neurocutaneous group of dysplasia, the author attempts to classify the patient described.
Adult↗
[Quantitative evaluation of rhinomanometric curves. A new simple method].
With the use of a new evaluation method, the rhinomanometric curve is quantified with only two measurements, both in the laminar and in the turbulent part of the curve. 1) The volume flow measured at a constant delta p of 15 mm of water defines the volume flow increase in the initial, more laminar part of the curve, and is in most cases a sufficient measure of the conductivity of the nose. The rule that governs the addition of parallel resistances is not broken when determining the bilateral breathing resistance. 2) The per cent volume increase (delta V) upon doubling the pressure difference (from 15 to 30 mm of water or, where conductivity is high, from 7.5 to 15 mm of water) quantifies the further increase of the curve and allows to distinguish characteristic from abnormal shapes of the curve. delta V gives an indication of the amount of turbulence in higher flows. The smaller the per cent volume increase the greater the turbulence. An increase by less than 41% indicates total turbulence, and under 25% delta V indicates a one-way stenosis by additional factors that cause narrowing of the lumen. The per cent volume increase (delta V) upon doubling delta p is a simple and easily understandable measurement. It is therefore superior in its simplicity to formula values such as resistance quotient, coefficient of resistance and increase of angle. The use of constant values of delta p (7.5, 15, 30 mm of water) ensures the comparability of the results. This procedure is applicable in both high and low air conductivity of the nose and is therefore suitable for statistical analysis. Furthermore, there is the possibility of an automatic evaluation of the rhinomanometric curve.
Airway Resistance↗
Regulation of proinflammatory cytokines in seasonal allergic rhinitis.
BACKGROUND: Mediators and cytokines have been demonstrated to be released due to nasal allergen exposure in sensitized subjects, but little is known about the release of cytokines and their antagonists under natural conditions. METHODS: Mediators - histamine, eosinophilic cationic protein (ECP), leukotrienes (LT) C4/ D4/E4 - and cytokines - interleukin (IL)-1beta, IL-8, IL-1 receptor antagonist (ra) - were measured in nasal secretions throughout the grass pollen season (6 visits) and for 6 weeks thereafter (3 visits) in patients with seasonal allergic rhinitis (n = 13) and compared to controls (n = 12). A second study was performed comparing nasal secretions of 13 subjects allergic to house dust mite to 8 controls. RESULTS: Compared to controls, leukotrienes and ECP were significantly elevated at nearly all time points in and postseason in the allergic group. Whereas IL-1beta was significantly elevated throughout the study period, IL-1ra was significantly decreased from visit 1 to 3. IL-8 showed no increase compared to controls. Data from subjects with perennial allergic rhinitis supported these findings and additionally demonstrated decreased concentrations of IL-8 and myeloperoxidase in secretions compared to controls. CONCLUSION: Allergic rhinitis represents a persistent inflammation in terms of an activation of eosinophils and constant upregulation of the proinflammatory cytokine IL-1beta in the pollen season and thereafter. We additionally could demonstrate a dysfunction of the anti-inflammatory capacity, i.e. IL-1ra, a naturally occurring antagonist. Persistent inflammation may furthermore lead to the dysregulation of local cellular immunity by reducing the number and activity of neutrophils on the mucosal surface.
Adult↗
Proinflammatory cytokines: measurement in nasal secretion and induction of adhesion receptor expression.
We recently demonstrated that interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6 and IL-8 can be found in nasal secretions from allergic rhinitis patients under artificial and natural conditions. By ELISA measurements, significantly elevated baseline levels for IL-1 beta, IL-6 and IL-8 were found in seasonal allergic compared to control subjects. Within the first 2 h after nasal allergen challenge, IL-1 beta and TNF are secreted, whereas IL-6 and IL-8 showed a slow increase over 6-8 h. All cytokine levels returned to baseline within 24 h after exposure. Repeated measurements at 4-week intervals in perennial allergic rhinitis subjects (n = 27) showed significant correlations between IL-1 and IL-8, IL-6 and IL-8 and IL-6 and the symptom score (visual analogue scale). The IL-1 receptor antagonist IL-1ra was found in great molar excess in the secretions and correlated significantly with IL-8, but not IL-1 beta. In an in vitro assay using fresh nasal mucosa of grass-pollen-allergic subjects, we were able to demonstrate a strong and rapid induction of E-selectin adhesion receptor expression on endothelial cells by allergen, IL-1 beta and TNF. The adhesion receptor expression was markedly inhibited by soluble IL-1 receptors, sTNF-R and IL-1ra. These data indicate a key role for inflammatory cytokines in the regulation of allergic inflammation.
Allergens↗
The common cold at the turn of the millennium.
Upper respiratory tract infections are one of the most common infectious diseases in man and are characterized by transient, relatively mild symptoms. Human rhinoviruses are known to be the major causative agent in adult common colds and their relative importance has further increased with the use of the sensitive RT-PCR technique. Characteristic for a common cold is the selective neutrophil recruitment and time-limited increase in mediator, cytokine, and chemokine concentrations that orchestrate chemotaxis, transmigration, and activation of inflammatory and immunocompetent cells. Common cold symptoms are found to correlate to rhinovirus-induced IL-8 elaboration and neutrophil activation. Treatment of rhinoviral upper respiratory tract infections consists of an inhibition of viral infection by antiviral agents and/or a reduction of symptoms by damping the host inflammatory response.
Adult↗
Nasal polyposis: from cytokines to growth.
Nasal polyposis (NP) is a chronic inflammatory condition that is mostly characterized by an infiltration of eosinophils. How this eosinophilic inflammation leads to polyp formation remains largely unclear. In order to identify the most important factors in polyp growth, first we report the histologic features of two early stage manifestations of eosinophilic nasal polyps compared to their surrounding normal mucosa and mature polyps from the same patients. Histomorphologic analysis of these early stage manifestations of NP showed the presence of eosinophils, forming a subepithelial cap over a pseudocyst area that was filled with albumin. In mature NP, a large pseudocyst area containing albumin was surrounded by subepithelial eosinophilia. Second, in an approach to quantify and to study possible relations between eosinophilic inflammation and changes in extracellular tissue components we measured interleukin-5 (IL-5), eotaxin, eosinophil cationic protein (ECP), leukotrienes (LTC4/D4/E4), transforming growth factor-beta 1 (TGF-beta 1), fibronectin, hyaluronic acid, and albumin in nasal tissue homogenates of 31 subjects. Nasal polyp samples (n = 16) were obtained during routine endonasal sinus surgery, whereas control non-polyp samples (n = 15) from subjects with (6) and without (9) allergic rhinitis were obtained from the inferior turbinate during septum surgery. In the group of polyp patients 11 received no treatment, whereas 5 were treated with oral glucocorticoids (GCS) within 4 weeks before surgery. IL-5 was measurable in 8 of 11 untreated NP, whereas IL-5 could not be detected in all 15 controls nor in 4 of 5 oral corticoid-treated polyps. The comparison between the untreated polyp group and controls showed significantly higher concentrations of IL-5, eotaxin, ECP, and albumin in polyp supernatants, whereas TGF-beta 1 was significantly lower. In the oral GCS-treated group, ECP and albumin were significantly reduced compared to untreated nasal polyps. The same tendency, but not reaching significance, was seen for eotaxin and fibronectin, while no difference was found for LTC4/D4/E4 and hyaluronic acid between the groups. Our observations suggest a deposition of albumin (and possibly other plasma proteins) and extracellular matrix proteins, which may be regulated by the subepithelial eosinophilic inflammation, as a possible pathogenic principle of polyp formation and growth. IL-5 and eotaxin are found to be key factors for eosinophilic accumulation and activation in NP. Oral corticoid treatment may lead to the shrinkage of NP by downregulation of the eosinophilic inflammation and reduction of the extravasation and deposition of albumin in NP.
Albumins↗
Cytokines in nasal polyposis, acute and chronic sinusitis.
Cytokines are potent biologic factors involved in the regulation of inflammation, immune defense, and wound healing. Recently, growing interest has developed in the role of cytokines in chronic sinusitis and nasal polyposis. In the present study, we investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a specific form of rhinosinusitis is associated with the expression of a certain cytokine profile. Sinus mucosa from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8) and controls of turbinate mucosa (n = 7) were sampled. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, interferon-gamma) of tissue homogenates was measured using ELISA technique. In acute sinusitis, the synthesis of proinflammatory cytokines and of the neutrophil chemokine IL-8 and IL-3 appeared to be upregulated. Chronic sinusitis mucosa demonstrated no significantly increased concentrations of the measured cytokines. In bilateral nasal polyposis, but not in antrochoanal polyps, the eosinophil related cytokine IL-5 was strongly upregulated. From these findings, it appears that specific cytokine patterns are found in different forms of sinusitis, and that IL-5 may represent the most important cytokine responsible for tissue eosinophilia in nasal polyposis.
Acute Disease↗
Cytokines and adhesion molecules in allergic rhinitis.
This review summarizes our current knowledge of nasal allergic inflammation based on studies of cytokines, chemokines, and adhesion molecules in allergic rhinitis. The article also includes some aspects of viral rhinitis. Due to artificial or natural allergen exposure, an increase in the number of eosinophils and basophils, mast cells, IgE-positive cells, macrophages, monocyte-like cells, Langerhans cells, and activated T-cells can be observed within the mucosa and on the mucosal surface. Mediators are known to be released in response to allergens, but do not seem to be adequate to initiate the cell recruitment. After antigen challenge, the release of proinflammatory and regulatory cytokines could be demonstrated, and TH2-type cytokine mRNA upregulation in allergic mucosa has been shown. Proinflammatory cytokines initiate an adhesion cascade and activate T-cells that create an "atopic" cytokine environment within the tissue, which also may be linked to the long-term selective recruitment of eosinophils. However, the acute selective migration of eosinophils after allergen challenge is not fully understood, nor is the role of chemokines in allergic and viral rhinitis. Allergic rhinitis clearly represents an inflammatory reaction.
Allergens↗