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Biomedical subjects

H Mosbech

Publications and source records attributed to H Mosbech.

At least 55 records · Page 3Linked to original sources
PubMed1990

Who will benefit from hyposensitization? Predictive parameters in house dust mite allergic asthmatics.

The aim of this study was to assess the ability of various data collected before treatment to predict the therapeutic benefits of hyposensitization. Thirty-one asthmatics were hyposensitized with extract from the house dust mite Dermatophagoides pteronyssinus (Dp) for 2 years, 15 comparable patients served as controls. The treatment extract was either modified by coupling to monomethoxypolyethylene glycol (mPEG) or administered in a diluent containing Al(OH)3. Improvement would be either a greater than or equal to 10-fold increase in bronchial tolerance to Dp or an overall clinical effect judged from questionnaires plus diary cards. Patients improving in bronchial Dp-sensitivity after 1 year had been more sensitive to DP pre-treatment in bronchi and in basophils, and had a lower FEV1 compared with the patients not improving (P less than 0.05). Occurrence of late-phase bronchospasm to pre-treatment Dp-challenge increased the chance of clinical improvement approximately 3-fold (P less than 0.05). A certain mite exposure seems to be a condition of an improvement in symptoms/medication. In patients improving, the median allergen concentration on mattresses was equivalent to 1,000 mites/g compared with less than 250 mites/g in patients showing no clinical improvement (P = 0.1). Information on Dp-specific IgE, IgG, IgG subclasses, Dp-sensitivity in skin, nose and eyes, age, and duration of symptoms did not permit any prediction of therapeutic effect.

Animals↗
PubMed1989

A comparison of two RAST methods and skin prick testing in the diagnosis of wasp venom allergy.

With the aim of evaluating the correlation between skin prick test and two radioallergosorbent tests (RAST) using paper (P-RAST) and Al(OH)3 (Al-RAST) as sorbent materials, 45 consecutive patients known to have been stung by wasp within 6 months were examined. Four patients had a normal reaction, four a large local reaction and 37 a systemic reaction. We found a good correlation between a systemic reaction and a positive P-RAST. Fifty-one per cent of patients with a systemic reaction had a negative Al-RAST, whereas only 8% had a negative P-RAST. Eight per cent of patients with a systemic reaction had a negative SPT. In the eight patients without a systemic reaction, the same patient reacted positively in Al-RAST and P-RAST.

Adolescent↗
PubMed1989

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. I. Clinical effect evaluated by diary cards and a retrospective assessment.

Forty-six asthmatics with verified allergy to the house dust mite, D. pteronyssinus (Dp), participated in a double-blind study comparing the effect of 2 years' hyposensitization with two different Dp extracts. Two groups received either monomethoxypolyethylene glycol modified (mPEG) Dp extract or the corresponding non-modified extract, and a third group acted as controls receiving no injections. Medicine consumption, symptom scores, and peak expiratory flow (PEF) were recorded daily from September to December prior to and after 6 and 18 months of treatment. Changes were calculated choosing changes greater than or equal to 10% as relevant. In addition, patients were asked to give their direct assessment of the clinical effect at the end of the study. After 6 months, there was an improvement in symptoms + medication in 11/14 of Dp-treated, 6/17 of the mPEG-Dp group (P greater than 0.05) and 3/15 of openly treated controls. Few patients had changed in PEF. During the second year, several Dp-treated relapsed and some controls improved. At the end of the study the same improvement rate was seen in all groups. Similarly, the retrospective questionnaire data did not disclose any significant differences between groups after 2 years. In conclusion, hyposensitization with unmodified Dp extract seemed to have a favourable short-term effect on bronchial symptoms + medication in the majority of patients. When mainly on maintenance dose, the beneficial effect was reduced. The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses. Changes in medicine and symptom scores only partly correlated to retrospective assessment, thus stressing the problems in this kind of evaluation.

Animals↗
PubMed1989

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. II. Effect evaluated by challenges with allergen and histamine.

In a 2-year study, 46 asthmatics with verified allergy to the house dust mite D. pteronyssinus (Dp) were included either as controls (Ctls) or receiving hyposensitization (HS) with unmodified or monomethoxypolyethylene glycol (mPEG) modified Dp-extract. Patients were monitored by annual challenges with histamine in bronchi, and Dp allergen in bronchi, nose and conjunctiva. mPEG-modified extract was not inferior to unmodified Dp-extract; both were to some extent able to improve tolerance to Dp and histamine in bronchi and to Dp in nose and eyes. During the 1st year, the bronchial sensitivity to Dp decreased significantly in the HS groups but not in the Ctls. During the 2nd year, improvement was more pronounced in the Ctl group. The relative increase in Dp or histamine tolerance did not differ significantly between groups after either 1 or 2 years; the only exception was conjunctival sensitivity, which in the Ctl group was unchanged, and a 10-fold increase in tolerance in the HS groups. No direct benefit was seen on late-phase bronchial reactions. In patients with improved pulmonary symptoms a tendency was seen towards reduced sensitivity to histamine and Dp. Variation within groups was extensive.

Animals↗
PubMed1988

Control of house dust mites by electrical heating blankets.

The contents of house dust mites, Dermatophagoides (D), in 10 beds supplied with electrical heating blankets (EHBs) and in 10 control beds were followed for 1 year. All beds were in regular use during the study period. Dust from mattresses and EHBs was collected monthly and analyzed for D by microscopy. Blankets were turned on during daytime and were washed every 3 months. For each bed the median concentration of D during the entire period was related to initial value. In the beds supplied with blankets, the overall median was 52% compared to 122% in the control beds (p less than 0.05). The difference between the two groups of beds was observed within the first month. Major antigens from D were reduced to 32% in the beds supplied with blankets and increased to 120% in the control beds (p less than 0.05). Climatic conditions were measured beneath the blanket in a spare bed. When beds were covered by eiderdown, temperature was increased by 26 degrees C, and the relative humidity was decreased by 24% within 3 hours. In conclusion, EHBs appear capable of reducing relative humidity and concentration of house dust mites on mattress surfaces.

Allergens↗
PubMed1988

Cell-mediated immunity assessed by skin testing (Multitest). II: Correlation between responses from arm and back.

In 60 healthy adult volunteers and 58 patients with gastrointestinal disease a test system (Multitest) consisting of a plastic disposable multiple-puncture device capable of simultaneously applying seven delayed-type hypersensitivity antigens and a glycerin/saline diluent (negative control) was assessed. The Multitest device was applied on both the inner side of the forearm and on the back for assessment of cell-mediated immunity (CMI). The antigens used were two toxoids, tetanus and diphtheria, three bacterial antigens, Streptococcus, tuberculin and Proteus and two fungal antigens, Candida and Trichophyton. A scoring system based on both number and size of positive response revealed a median "score" on arm and back of 19 mm and 14 mm respectively, in the healthy volunteers and a median "score" of 12 mm and 8 mm respectively in patients with gastrointestinal disease. In both groups a significant difference was found between back and arm (P less than 0.01). The coefficient of determination (r2) shows that only 64% of the variability in scores on the back is explained by the regression line. Therefore, scores obtained from tests on the back cannot be interpreted with reference to normal values originating from tests applied to the inner side of the forearm.

Adult↗
PubMed1988

Does the effect of immunotherapy last after termination of treatment? Follow-up study in patients with grass pollen rhinitis.

In a previous study, 39 adults with grass pollen allergy were hyposensitized for approximately 2 1/2 years. Treatment was performed in a double-blind fashion with extract made from timothy grass--either Alutard SQ 20-component extract or a purified 2-component extract, including only the two major allergens Phl p V and VI. Standardized symptom + medicine scores and challenge tests demonstrated a clinical effect, most markedly in the group receiving 20-component extract. Six years after termination of treatment, 38 patients could be approached and 16 in each group were examined and repeated symptoms scoring during the subsequent season. When adjustment for variations in pollen counts were made, medicine + symptom scores stayed low during the follow-up period. Specific IgE-antibodies against timothy showed an increase to initial values during the same period, whereas total IgE antibodies remained low. Skin prick test reactions with timothy allergen tended to increase but were still smaller than before treatment. Retrospectively, the patients reported symptoms to have stabilized or even further decreased after termination of treatment, with no significant difference between groups. In conclusion, the clinical effect was still present more than 6 years after termination of treatment. Some in vitro parameters tended to return to pretreatment level. The spontaneous course of the disease in non-hyposensitized patients was not investigated.

Adolescent↗
PubMed1988

Modification of house dust mite allergens by monomethoxypolyethylene glycol. Allergenicity measured by in vitro and in vivo methods.

In animal models, allergen modification by coupling to monomethoxypolyethylene glycol (mPEG) molecules can reduce allergenicity of the extract and makes the allergen capable of suppressing boosted IgE response. To investigate in a human system the degree of attenuation implied by a mPEG modification of a house dust mite (Dermatophagoides pteronyssinus) extract, 55 adults with asthma caused by house dust mites were tested by skin prick test (SPT) and histamine release assay (HR). RAST inhibition was performed on sera from 6 additional patients. Modified extract containing 0.42 mmol mPEG/g protein was used for the analyses. In order to get the same response of the two extracts when assessed by HR and SPT, a median increase in concentration of 10-fold of the mPEG-modified extract compared to the unmodified extract was needed. Interindividual variation was limited. Sixty-four to 72% needed a dose increase within +/- half a decade from this value. In 42-49% of the patients, results from SPT and HR deviated less than half a decade. The relative potency of the modified extract as measured by RAST inhibition was reduced to 17-78% (mean 39%). Reduced allergenicity would by itself mean less side effects in immunotherapy. When planning such therapy it is important to know that mPEG modification reduces the allergenicity to a similar extent in a majority of patients.

Allergens↗
PubMed1988

Interleukin-1 production by monocytes from patients with allergic asthma after stimulation in vitro with lipopolysaccharide and Dermatophagoides pteronyssinus mite allergen.

Monocytes from 6 patients with asthma and positive bronchial challenge with extract from the house dust mite Dermatophagoides pteronyssinus (Dp) were stimulated with lipopolysaccharide (LPS) and allergen extract from Dp. In order to neutralize putative endotoxin contamination of the allergen extract, some cultures were incubated in the presence of polymyxin B. Interleukin-1 (IL-1) activity was assayed by the comitogenic activity of the crude monocyte supernatants on phytohemagglutinin-stimulated murine thymocytes. Our results suggest that, upon stimulation with LPS and allergen, monocytes from atopic patients possess a normal capacity to produce IL-1. Like monocytes from healthy controls, patient monocytes do not produce IL-1 spontaneously. The specificity of the allergen stimulus is not well-defined, and further characterization of the IL-1-inducing property awaits the availability of endotoxin-free allergen preparations.

Adult↗
PubMed1988

Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors.

Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leucocytes from normal individuals. At first, the system was optimized with regard to donor cells and anti-IgG4 antibody: among 3 normal individuals with cells showing high, medium and low responses to anti-IgE, only the high responder showed a reproducible, but low response to anti-IgG4. This response was consistent when testing anti-IgG4 from different sources, and could be potentiated by a phorbol ester TPA, although not up to the level of anti-IgE. The cells from the high responding donor and a monoclonal anti-IgG4 were selected for further studies. Serum pools from patients allergic to house dust mite (Dermatophagoides pteronyssinus) were used for passive sensitization. The pools contained allergen-specific IgE with or without concomitant IgG4 of the same specificity. The sensitized basophils reacted to anti-IgE and allergen, but to anti-IgG4 only to a small extent. However, when these serum pools were fractionated by affinity chromatography, only the IgE fractions and not the IgG4 fractions made the cells reactive towards specific allergen. It was still possible to elicit a reaction by triggering IgE with anti-IgE, whereas only a small reaction was seen, when IgG4-sensitized basophils were provoked with anti-IgG4. We conclude that IgG4 does not sensitize normal basophils.

Basophils↗
PubMed1987

Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology.

Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 micrograms usually protects from life-threatening reactions. However, in some patients 200 micrograms are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.

Adult↗
PubMed1987

High dose grass pollen tablets used for hyposensitization in hay fever patients. A one-year double blind placebo-controlled study.

Previous, placebo-controlled clinical trials with oral hyposensitization in grass pollinosis have been disappointing. Since the results possibly could be explained by too low doses of ingested allergens, the present study was initiated to evaluate the effect of high doses of allergens. Forty-two adults with symptoms in the grass pollen season and with grass pollen sensitivity demonstrated by skin prick test and conjunctival provocation test were included. Enterosoluble tablets were administered daily for 1 year. Twenty-two patients, who completed the study, received placebo and 17 mixed grass pollen allergens from rye grass, timothy grass, cultivated rye and velvet grass. Evaluated either by self-assessment or by symptom and medicine score before and after treatment, the group receiving pollens did not improve clinically compared the controls. During the study, conjunctival sensitivity decreased equally in the two groups, and changes in specific IgE, allergen-induced histamine release from blood cells and skin prick test were insignificant and with no difference between groups. Five patients, who received pollen allergens, had episodes of urticaria or angioedema, and a further three patients on the same treatment had slight gastrointestinal side effects. In conclusion, enterosoluble grass pollen allergens in contrast to birch pollens did not have any therapeutic effect, even in doses more than 4,000 times higher than those used for subcutaneous hypersensitization. The reason may be degradation of allergens before the immune system is reached.

Adolescent↗
PubMed1987

House dust mite asthma. Correlation between allergen sensitivity in various organs.

Fifty asthmatics, candidates for hyposensitization with the house dust mite Dermatophagoides pteronyssinus (Dp), went through a series of allergy tests to evaluate the sensitivity of different organs to Dp. All patients were exposed to bronchial challenge with histamine and bronchial, nasal and conjunctival challenge with Dp, skin prick test (SPT) with Dp, analyses for Dp-specific histamine release from blood cells (HR) and for anti-Dp-IgE in serum (RAST). Results from 40 patients reacting positively in all tests were further analysed. Sensitivity to Dp in the various organs did not parallel, but a fair correlation was demonstrated between pulmonary allergen sensitivity and HR (r = 0.65, P less than 0.001), and between pulmonary sensitivity to allergen and to histamine (r = 0.47, P less than 0.001). Combined variations in HR and in (unspecific) bronchial sensitivity to histamine explained 53% of the variation in bronchial sensitivity to the allergen. This parameter showed less correlation to RAST and SPT (r = 0.31 and r = 0.35, P greater than 0.05). The results indicate that bronchial allergen challenge cannot be replaced by similar challenge of other organs, since the sensitivity of the mucosa in different organs of the same patient seems unrelated. Diagnosis should therefore be based on challenge of the organ with dominating clinical importance. In our selected group of patients, however, it was indicated that a substitution of the result of bronchial allergen challenge by measurement of unspecific bronchial reactivity, together with information on the general allergen sensitivity on a cellular level, might be possible. The unpleasant symptoms of the immediate and late bronchial reactions to allergen challenge could thereby be avoided.

Allergens↗
PubMed1987

House dust mite-induced histamine release from washed blood cells. Evaluation of effect parameters.

In a selected group of 60 house dust mite allergic asthmatics, the correlation between the bronchial sensitivity to house dust mite and effect parameters of mite-induced histamine release from washed blood cells was evaluated. Using a sensitive glass microfibre-based method, a significant positive correlation (r = 0.60; P less than 0.001) was found between bronchial allergen sensitivity and basophil cell sensitivity expressed as the house dust mite concentration necessary to give half the maximum histamine release. No correlation was found between bronchial sensitivity and other parameters of the histamine release response. This way of determining the histamine release from washed blood cells is a simple and valuable alternative to bronchial allergen challenge.

Animals↗
PubMed1987

Cell-mediated immunity assessed by skin testing (Multitest). I. Normal values in healthy Danish adults.

The Multitest CMI system consists of a disposable multiple puncture device that simultaneously applies seven standardized recall antigens for assessment of cell-mediated immunity (CMI). The seven antigens included were toxoid from Clostridium tetani and Corynebacterium diphtheriae, tuberculin, plus antigens from streptococcus (group C), Candida albicans, Trichophyton mentagrophytes, and Proteus mirabilis. A population of 352 healthy Danish adults, aged between 17 and 90 years, was tested to determine the incidence and size of delayed-type hypersensitivity (DTH) responses. All but six healthy adults (98%) responded to one or more antigens, the median number of positive responses being four in males and three in females. The incidence of positive responses ranged from 91% for tuberculin to 11% for trichophyton. The number of positive responses declined with age, being somewhat faster in females than males. Six of the seven antigen response rates were significantly lower in the over 65-years-olds, the only exception being trichophyton, and for four of the seven antigens significantly lower in females compared to males. When correlated to age and sex no major differences were found with regard to the size of response to the seven antigens except that the tuberculin response was larger in males. A scoring system based on both number and size of positive responses revealed significant age and sex related differences. The median "score" in 17-65-year-old males and females were, respectively, 17 mm and 14 mm compared to 13 mm and 8 mm in those over 65 years old (P less than 0.001 for both comparisons).

Adolescent↗