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Biomedical subjects

H J Malling

Publications and source records attributed to H J Malling.

At least 73 records · Page 4Linked to original sources
PubMed1990

Diagnosis of mold allergy by RAST and skin prick testing.

Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum.

Adult↗
PubMed1989

Maxisorp RAST. A sensitive method for detection of antigen-specific human IgE in culture fluids.

For determination of allergen-specific IgE in cell culture supernatants and other highly diluted IgE preparations a radioallergosorbent test (RAST) based on high adsorption polystyrene test tubes has been developed ("Maxisorp RAST"). Cladosporium herbarum extract was used as a model allergen but timothy grass pollen, house dust mite and dog dander showed similar results. The test showed specificities of both allergen and immunoglobulin isotype and significant correlations (r = 0.67-0.88) with established RAST procedures were found. Based on immunosorbent-purified allergen-specific IgE the estimated sensitivity was within the order of 150-300 pg allergen-specific IgE per ml. The within-assay variation was 4-9% and the inter-assay-variation 17-29%. The Maxisorp RAST is useful as an inhibition assay for quantitating allergenic activity down to 0.1 biological units/ml of allergen extracts.

Allergens↗
PubMed1989

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1988

Diagnosis and immunotherapy of mould allergy. VII. IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium.

The IgG subclass response was evaluated by a sensitive allergen- and subclass-specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG1 response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG1 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects.

Adolescent↗
PubMed1988

Diagnosis and immunotherapy of mould allergy. VIII. Qualitative and quantitative estimation of IgE in Cladosporium immunotherapy.

The interrelation of in vitro IgE-mediated parameters, i.e. serum-specific IgE (RAST), basophil cell-bound specific IgE, and histamine release from basophil leucocytes was investigated in a 1-year placebo-controlled, double-blind Cladosporium immunotherapy study involving 22 adult asthmatics. The intense and early burst (within 6 weeks of immunotherapy) of serum-specific IgE did not result in a corresponding increased binding of specific IgE molecules to basophils. Cell-bound IgE increased in the Cladosporium season in both groups at the same time as serum levels of specific IgE declined in the Cladosporium group. In the placebo group histamine release from circulating basophils paralleled changes in basophil-bound IgE. In Cladosporium-treated patients, histamine release cell sensitivity after a lag phase (during immunotherapy dose-increase) declined two log steps, i.e. the cells became less responding in spite of a significant increase in cell-bound IgE. To further evaluate the sensitizing capacity of circulating specific IgE, passive sensitization studies were performed using basophils from a single donor. Although sera taken at the maximal IgE-response showed an enhanced capacity of passive sensitization, the ratio between RAST and passive sensitization capacity increased significantly in Cladosporium-treated patients, implying a less than expected sensitization capacity of immunotherapy-induced specific IgE. The lack of active binding of IgE to basophils might be explained by a reduced Fc-affinity of immunotherapy-induced IgE in contrast to the Cladosporium-seasonally induced IgE. Regarding the decrease in histamine release in Cladosporium-treated patients in spite of an increased amount of cell-bound specific IgE, immunotherapy may initiate a decrease in mediator releasibility which is not caused by a reduction in the number of Fc-receptors but rather some yet unknown subcellular mechanisms regulating the histamine release. The described changes in IgE-mediated parameters do not seem to be caused by interference with either specific IgG1 or IgG4. Changes in histamine release in the Cladosporium season were the only IgE-mediated parameter significantly related to the graded clinical efficacy of immunotherapy.

Adult↗
PubMed1987

Allergenicity of alum-precipitated grass pollen extracts with different RAST activity.

The biological potency of therapeutic allergen extracts is fundamentally important in terms of maximal security of immunotherapy, especially when changing batches. As regards pyridine-extracted alum-precipitated allergen preparations, the potency is commercially controlled by the RAST technique. In the present study, titrated intradermal tests were performed in thirty-three adult grass-pollen rhinitis patients with three ten-fold dilutions of two batches of Allpyral 5-grass mix with different RAST activity. The difference in potency was estimated as the horizontal distance at the midpoint of the two dose-response curves after performing linear regression on the log-dose/log-weal area response, and as the concentration of each batch eliciting a weal equal to the histamine HC1 0.1 mg/ml reference. The difference in potency as estimated by RAST was a factor 5.0 vs a factor 8.3 and 7.2 (median) estimated by the horizontal distance and histamine-equivalent reaction, respectively. Considering the biological variation, the RAST-estimated difference in potency is in the same order as that found by skin test. It is, therefore, concluded that the routine control of new production batches by RAST is acceptable with the use of standardized reference sera as regards alum-precipitated grass pollen allergen extracts.

Humans↗
PubMed1987

High IgG4 antibody level is associated with failure of immunotherapy with inhalant allergens.

We have analysed all available data on the relationship between IgG4 Ab level and clinical effect of immunotherapy (IT) with inhalant allergens. The data from three of the seven independent studies could, without reservations, be analysed by a joint statistical analysis. We found that late high IgG4 Ab level, measured at the end of IT, was strongly associated with treatment failure (P = 6.54 x 10(5); n = 67). The ratio of risks for treatment success in the group with late low IgG4 Ab level was 1.82, whereas the ratio of risks for treatment failure in the group with late high IgG4 Ab level was 11.4. The data from a fourth, presumably comparable, study further supported the existence of an association between high IgG4 Ab level and treatment failure. In contrast, two other studies found that high mean IgG4 Ab level was associated with good clinical response. Possible reasons for this apparent discrepancy are discussed. We also found that early high IgG4 Ab level, measured within 3 months after initiation of IT, was strongly associated with treatment failure after 1-2 years of IT (P = 1.05 x 10(-4); n = 30). The sensitivity and specificity of early high IgG4 Ab level as indicator for treatment failure was 100% and 83%, respectively. At the prevalences found in the present study, the predictive value of early high IgG4 Ab level for treatment failure was 0.6, whereas the predictive value of early low IgG4 Ab level for treatment success was 1.00.

Administration, Inhalation↗
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

Quantitative skin prick testing. Dose-response of histamine- and allergen-induced wheal reactions.

Dose-response curves of histamine- and allergen-induced wheal areas were evaluated in seven normals (defined as negative skin prick test (SPT) to inhalant allergens and no clinical signs of allergy), seven latent allergics (positive SPT without allergic symptoms), and 20 manifest allergics (positive SPT and allergic symptoms). Three concentrations of histamine HCl (1, 10 and 100 mg/ml) and three 10-fold concentrations of nine inhalant allergens (birch, timothy, mugwort, horse, dog, cat, house dust mite, Cladosporium and Alternaria) in concentrations 1,000 10,000 and 100,000 BU/ml were used and linear regression was performed on the skin reactions. Only tests with an SD% less than 40%, a log slope greater than 0.1, and a correlation coefficient greater than 0.95 were accepted. In normals a significantly higher concentration of histamine was needed to elicit a wheal reaction of 2 mm2 (end-point) compared with allergics. Likewise, normals had a significantly higher slope i.e. steeper dose-response curve of histamine than manifest allergics. The slope of the allergen-induced wheal area was significantly higher than the histamine slope. No relation between corresponding slope of histamine and allergens was found (Rho = 0.15). The skin sensitivity equivalent to histamine calculated as the allergen concentration eliciting a wheal equal to histamine showed a median increase of 5-6 fold in allergen concentration by a 10-fold increase of histamine concentration. The highest correlation between the wheal area of a single allergen concentration and the skin sensitivity was found for allergen concentration 100,000 BU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Diagnosis and immunotherapy of mould allergy. VI. IgE-mediated parameters during a one-year placebo-controlled study of immunotherapy with Cladosporium.

The IgE-response was evaluated by skin prick test, bronchial provocation test and RAST in a 1-year placebo-controlled double-blind immunotherapy study. Eleven adult asthmatics were treated with a Cladosporium allergen preparation and 11 comparable patients received histamine placebo. The bronchial sensitivity (PC20) decrease greater than 0.5 log step in 8/11 (73%) Cladosporium-treated versus 3/11 (27%) in the placebo group. Corresponding figures for skin prick test sensitivity was 10/11 (91%) and 1/11 (9%) respectively. Circulating IgE showed a temporary boost in the Cladosporium group and then values approaching the pretreatment value. Only minimal and insignificant changes were found in the placebo-treated patients. Changes in IgE-reactivity were not related to allergen dose, clinical efficacy or to the occurrence of side effects. Some interrelation between changes in skin prick test, bronchial provocation test and RAST was found indicating a differentiated effect of immunotherapy on various IgE compartments. In spite of the pathogenetic role of IgE in allergic diseases, changes in IgE-reactivity do not seem directly involved in the mechanisms underlying the clinical efficacy of immunotherapy but might be of importance in a complex interaction with other immunological parameters.

Adult↗
PubMed1987

Results of biological standardization with standardized allergen preparations.

The aim of biological standardization (BS) is to equilibrate the activity (potency) of allergen extracts from different source materials. This was done by performing skin prick tests (SPT) on patients who were sensitive to one of the following 10 allergens: Birch, alder, hazel, timothy, rye grass, velvet grass, cultivated rye, mugwort, D. farinae and Cladosporium herbarum. Patient sensitivity varied within a range of three to four powers of ten for each allergen investigated. The weal size in each patient corresponding to that elicited by histamine 1 mg/ml was calculated using the model log (mean weal diameter) = a + b log (concentration). The correlation coefficients of the regression lines of the allergen dose response relationship were found to be greater than 0.85 in most cases. The median slope for all extracts was 0.24. The slope for Cladosporium was significantly steeper than that for pollens. The amount of material in microgram dry weight (d.w./ml) equal to 1000 biological units/ml (BU/ml) varied within a factor of three between species for all tested purified allergen preparations but Cladosporium. For Cladosporium, about 30 times more material was needed than for D. farinae. When using crude rather than purified material, it was necessary to use five to ten times more to elicit a reaction corresponding to 1000 BU/ml, but the difference was significant only for Cladosporium. The narrow range of allergen concentrations used by us as well as other investigators does not assure positive skin prick test results in all patients with clinical symptoms due to the allergen in question. Skin prick testing should therefore be done over a wide range of concentrations to improve the methods for BS.

Allergens↗
PubMed1986

A sensitive and reproducible method for the determination of subnanogram quantities of immunoglobulin E (IgE).

An immunoradiometric assay for immunoglobulin E (IgE) using high adsorption polystyrene test tubes as the solid phase (the 'Maxisorp' assay) is described. The sensitivity of the method was found to be 50 pg IgE/ml and the within-assay reproducibility was 3-7%. The accuracy was estimated by means of a comparison between the Maxisorp assay and paper radioimmunosorbent test (PRIST) and a correlation coefficient of 0.98 (P less than 0.001) was obtained. We conclude that the Maxisorp assay is a fast and reliable assay for IgE determination in cord blood, cell culture supernatants and other highly diluted IgE preparations.

Antibody Specificity↗