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Hans-Jørgen Malling

Publications and source records attributed to Hans-Jørgen Malling.

15 recordsLinked to original sources

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy.

BACKGROUND: Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. OBJECTIVE: In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. METHODS: Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. RESULTS: Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. CONCLUSION: Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. CLINICAL IMPLICATIONS: Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens.

Adult↗

[Anaphylaxis].

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Anaphylaxis↗

Out-of-season recollection of drug use for seasonal IgE-mediated rhinitis: useful but an overestimation.

BACKGROUND: The history of seasonal, IgE-mediated (allergic) rhinitis is often obtained postseasonally as a retrospective assessment. It is not known whether recollected drug use is representative for the in-seasonal medication history. OBJECTIVES: To investigate the agreement between in-seasonal and out-seasonal reports on drugs and drug doses, and to investigate whether retrospective assessment was sufficiently sensitive to detect the effect of intervention. MATERIAL AND METHODS: Thirty-five patients allergic to birch pollen were allocated to allergen-specific immunotherapy (SIT) or placebo in a double-blind study. Drug use was recorded daily during the season 2000 and out-seasonally 6 months after the seasons 1999 and 2000. The mean daily drug use was transformed into a 4-point categorical scale for simplicity and was calculated for the out-seasonal rating and for 6 in-seasonal periods of different durations. In-seasonal and postseasonal ratings were compared with the Cohen weighted kappa (kappa w). RESULTS: We observed a high level of agreement between in-seasonal and retrospective reports of drugs used (kappa w > 0.60) and drug doses (kappa w > 0.50). The highest agreement was observed for the in-seasonal day, week, or 2 weeks with the highest drug intake. Out-seasonal ratings significantly overestimated the daily oral and nasal antihistamine use compared with in-seasonal periods >2 weeks. Despite being comparable pretreatment, only the SIT group had a significant decrease in recollected total drug use during SIT. CONCLUSION: Out-seasonal recollection of hay fever drugs represented a period of a maximum 14 days. It appeared sufficiently sensitive to detect the effect of intervention.

Adult↗

[Allergy tests].

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Adult↗

Food allergy to apple and specific immunotherapy with birch pollen.

Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present.

Adult↗

Comparison of the clinical efficacy and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results.

PURPOSE OF REVIEW: Sublingual immunotherapy has been documented as clinically effective in controlled studies. Some concerns about the magnitude of disease severity reduction in relation to standard subcutaneous immunotherapy have been raised. The comparison with subcutaneous immunotherapy is important for giving recommendations on the use of sublingual immunotherapy in daily clinical practice. RECENT FINDINGS: Only three controlled comparative studies of sublingual and subcutaneous immunotherapy have been published. The methodology of the studies indicated that some study design deficiencies limited the interpretation of efficacy. Only one study used an optimal placebo-controlled, double-blind, double-dummy and randomized design. The studies are assessed with respect to a sufficient number of patients to detect statistically possible differences, the inclusion of patients, clearly defined outcome measures, doses of extract administered, and duration of treatment. In all three studies the reduction in disease severity was of the order of 50% with no significant difference between the two treatments. SUMMARY: The clinical efficacy of sublingual immunotherapy is based on three studies only, and a limited number of patients equal to the efficacy obtained by subcutaneous immunotherapy. Only limited information on long-term efficacy and preventative capacity are available. More data on these aspects are needed, but the restraint in using sublingual immunotherapy in the treatment strategy of allergic diseases does not seem to be evidence based. Future research should also focus on identifying which subsets of patients would most benefit from either of the two routes of immunotherapy administration.

Administration, Sublingual↗

CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells.

We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.

Apoptosis↗

Immunotherapy for rhinitis.

Allergen-specific immunotherapy in the treatment of allergic rhinitis has a well-documented clinical efficacy that indicates a statistically significant and clinically relevant reduction in symptom scores and the need for pharmacotherapy. The clinical efficacy of recently published studies is equivalent to or superior to the effect of standard anti-allergic drugs. Additional advantages are related to a downregulation of the allergic phenotype with the additional induction of a Th1 cytokine profile. The immunoregulatory capacity and the global downregulation of the allergic inflammation in mucous membranes might be important factors in the capacity to ensure long-term clinical efficacy (after termination of treatment) and the preventive capacity of immunotherapy in reducing the progression of rhinitis to asthma as well as deflowering the development of new sensitizations. Subcutaneous immunotherapy is optimal in severe allergic rhinitis with signs of bronchial hyperreactivity; however, sublingual immunotherapy might be an option for patients with milder disease.

Administration, Sublingual↗

Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults: a 3-year follow-up study.

BACKGROUND: The skin prick test is the allergologic test of choice, but asymptomatic skin sensitization to aeroallergens is common. However, no data in the literature describe the clinical phenotype of asymptomatic sensitized adults. OBJECTIVE: The purposes of this investigation were to provide a clinical characterization of skin test-positive subjects without symptoms and to ascertain the predictive values of common allergologic tests. METHODS: Asymptomatic adults with positive skin prick test results for birch (n = 15), nonatopic control subjects (n = 25), and birch pollen-allergic patients (n = 6) were followed through use of daily diary cards during 3 consecutive birch pollen seasons. At inclusion and at the 3-year follow-up visit, conjunctival and nasal challenges, intradermal late-phase reaction evaluation, and measurement of specific IgE were performed. RESULTS: Asymptomatic sensitized subjects defined a clinically significant phenotype between nonatopic and allergic subjects in terms of specific IgE levels and susceptibility to conjunctival provocation testing. Sixty percent (n = 9) of the asymptomatic sensitized subjects developed clinical allergy. This was associated with an initial birch skin prick test weal diameter of > or =4 mm, a positive conjunctival provocation test result, and specific IgE of > or =CAP class 2, as well as with the presence of other allergies. Specific IgE of > or =CAP class 2 was 87.5% predictive for allergy development, whereas a negative conjunctival provocation test result was 100% negatively predictive. Nasal provocation testing possessed no additional prognostic information. No changes in clinical phenotype were seen in nonatopic or birch-allergic subjects. CONCLUSION: Asymptomatic skin sensitization is a risk factor for later allergy development. At risk is any subject with target organ sensitivity, an elevated specific IgE level, and/or a skin prick test weal diameter of >4 mm.

Administration, Inhalation↗

Is sublingual immunotherapy clinically effective?

PURPOSE OF REVIEW: Sublingual immunotherapy has become increasingly popular and in some countries more allergic patients are treated by the sublingual route than the subcutaneous route. Evaluation of the scientific documentation for clinical efficacy is important before a treatment is used without restriction. This review critically analyses every placebo-controlled, double-blind study providing symptom/medication scores for the primary outcome; that is, a significant and clinically relevant reduction in disease severity of actively treated patients. RECENT FINDINGS: In total 23 papers fulfill the evaluation criteria; 26% are categorized as unequivocally effective, 35% are possibly effective (significant improvement in either symptom or medication scores), and 39% have no statistically documented efficacy. SUMMARY: The majority of papers have used an inadequate study design that may be responsible for the large number of inconclusive and negative studies. Before sublingual immunotherapy can be recommended as a routine treatment, more documentation for beneficial efficacy is needed.

Administration, Sublingual↗