Uffe Bodtger

The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

Background: There is only very limited documentation of the efficacy and safety of high‐dose subcutaneous birch pollen immunotherapy (IT) in double‐blind, placebo‐controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America.

Rhinitis symptoms and IgE sensitization as risk factors for development of later allergic rhinitis in adults

Background:  Rhinitis symptoms and IgE‐sensitization often mismatch. Asymptomatic sensitization is an established risk factor for later rhinitis, whereas it is not clear whether rhinitis is a risk factor for later development of IgE‐sensitization.

Vaccination for birch pollen allergy: comparison of the affinities of specific immunoglobulins E, G1 and G4 measured by surface plasmon resonance

Background Allergen‐specific immunotherapy (SIT) is associated with increased levels of allergen‐specific IgG in serum. However, it is not clear to what extent qualitative changes in the allergen binding capacity of IgG may be induced as well.

Clinical Impact of Endoscopic Ultrasound-Fine Needle Aspiration of Left Adrenal Masses in Established or Suspected Lung Cancer

Introduction: Correct lung cancer staging is pivotal for optimal allocation to surgical and nonsurgical treatment. A left adrenal gland (LAG) mass is found in 5 to 16%, and malignancy preclude surgery. Endoscopic ultrasound (EUS) is superior to other imaging procedures in visualizing LAG, but the impact of EUS-fine needle aspiration (FNA) on tumor, node, metastasis (TNM)-staging, treatment, and survival is unknown. Methods: The impact of EUS-FNA of the LAG on TNM staging, treatment, and survival was evaluated retrospectively in all patients (n = 40) referred to EUS during 2000–2006 for known or suspected lung cancer and where EUS disclosed an enlarged LAG. Conventional workup had preceded EUS. Results: EUS-FNA of an enlarged LAG altered the TNM staging in 70% (downstaged: 26 of 28 patients) and treatment in 48% (gained surgery 25%, avoided surgery 5%, surgically verified benign disease 5%, no cancer and no further workup 5%, and no cancer, control computed tomography, and then no further workup 8%). A malignant LAG lesion was found in 28% and was significantly associated with shorter survival. Conclusion: EUS-FNA of an enlarged LAG in patients with known or suspected lung cancer had a significant impact on TNM staging, treatment, and survival. The impact of routine visualization of the LAG in lung cancer workup needs to be prospectively validated.

Prognostic value of asymptomatic skin sensitization to aeroallergens

Purpose of reviewAsymptomatic skin sensitization to aeroallergens is frequently encountered in epidemiological studies and in everyday clinical life. Correct management of the condition is essential to avoid both progression into allergic disease and unnecessary intervention. Understanding immunological mechanisms in asymptomatic skin sensitization might provide new insights into the natural history and treatment of respiratory allergy. Recent findingsResearch on asymptomatic skin sensitization is rare, and the present review unites previous studies with recent findings. It is a common condition affecting 8-30% of the population when using a local standard panel of aeroallergens. Clinically, immediate but not late-phase reactions are induced by allergen challenge. Absent eosinophil stimulation and migration and low IL-5 levels appear to be sentinel mechanisms. Prospective studies show that 30-60% become allergic, depending on allergens and follow-up period. No prospective intervention studies have been performed; however, allergen avoidance seems efficacious in reducing allergy development to occupational and domestic allergens. Asymptomatic skin sensitization due to an erroneously positive skin test must be ruled out before allergen avoidance measures are initiated. SummarySurprisingly few papers exist on asymptomatic skin sensitization epidemiology and immunology, despite the intriguing question as to why symptoms do not develop in IgE-sensitized patients. It is a common condition and a risk factor for later development of respiratory allergic disease. Cross-sectional intervention studies suggest that allergy development is reduced by allergen avoidance. Immunologically, control of eosinophil stimulation and migration seems to be pivotal. How this control is maintained remains to be elucidated.

A rational clinical approach to suspected insulin allergy: status after five years and 22 cases

Aims  Allergy to recombinant human (rDNA) insulin preparations is a rare complication of insulin therapy. However, insulin preparations contain several allergens, and several disorders can resemble insulin allergy. Studies evaluating the diagnostic procedures on suspected insulin allergy are extremely few.

Vaccination for birch pollen allergy. Induction of affinity-matured or blocking IgG antibodies does not account for the reduced binding of IgE to Bet v 1.

Specific allergy vaccination (SAV) is associated with increased levels of allergen specific IgG in serum. It is not clear, however, to what extent qualitative changes in allergen binding to IgG may be induced as well. We therefore analyzed the binding of the major allergen in pollen of birch (Betula verrucosa) (Bet v 1), the major allergen in birch pollen, to serum IgG and IgE, separately and in competition. Sera from six birch pollen-allergic patients were obtained before and after 5 years of SAV, and binding was assessed with 125I-Bet v 1. Before SAV, IgG bound more than eight times the amount of Bet v 1 compared with IgE, and together they accounted for more than 85% of the serum binding capacity. While SAV induced minimal changes in IgE binding, the IgG binding capacities increased 6-32 times. In contrast, the binding avidities (K(d) 28-40pM) changed less than 20%, pre- and post-SAV IgG provided similar inhibition of Bet v 1 binding to IgE at equimolar levels, and cross inhibition studies between IgG and IgE showed low inter-individual differences. Following SAV, all sera reduced Bet v 1 binding to CD23(+) cells, correlating with reduced binding of Bet v 1 to IgE (P<0.001). These results show that high avidity IgG of low inter-individual difference in Bet v 1 binding quality is the dominant binding factor of Bet v 1 in sera of birch pollen-allergic patients, and that SAV-induced inhibition of binding of Bet v 1 to IgE can be explained mainly or solely by increased amounts of IgG.

Retrospective assessment of seasonal allergic symptoms: over‐rating but useful

Background The history of the severity of seasonal allergic symptoms is often obtained post‐seasonally as a retrospective assessment. Correct rating is essential when determining the efficacy of pharmaceutical treatment, indications for allergen‐specific immunotherapy (SIT), or inclusion into controlled clinical studies.

In vitro effects of monophthalates on cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells from allergic and non-allergic donors

It has recently been shown that plasticizers are present in indoor air dust, which may lead to human exposure via the inhalation route. Moreover, studies have indicated that plasticizers may possess adjuvant effects increasing the health damaging potential of allergens. The aim of this study was to investigate the in vitro effect of metabolites of phthalate plastisizers, such as whether an adjuvant effect is paralleled by changes of the cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells (PBMCs) from allergics and non-allergics. The toxicity monitored by cell viability was determined by incubating THP-1 cells with a 10-fold dilution series of monophthalates for 24 h. At different points in time cytokine expression (IL-1beta, IL-6, IL-12alpha (p35)) in THP-1 cells incubated with non-toxic concentrations of monophthalate (2-20 microg/ml)+/-LPS (1 microg/ml) were determined using Quantitative Competitive RT-PCR. PBMCs from allergics and non-allergics were incubated with monophthalate 220 microg/ml) for up to 48 h and cytokine expression (IL-4, IL-5, IFN-gamma) was measured using real-time PCR. The cytotoxic level of monophthalates is 20-200 microg/ml, depending on the individual monophthalate. There seems to be a correlation between increasing side-chain length and toxicity. Monophthalates did not induce changes in cytokine expression in THP-1 cells, though there is an increase when co-incubating with LPS. Cytokine expression in PBMC seems virtually unchanged when co-incubated with monophthalate, though mono-n-butyl phthalate (MBUP) tends to increase the level of IL-4 in PBMCs from allergic individuals. The two cellular models demonstrated the dynamics of regulated cytokine mRNA and are applicable for in vitro immunotoxicological investigations. The results regarding monophthalates suggest these to have a limited effect on cytokine expression in the monocytic cell line THP-1 and weak effect on cytokine expression in PBMCs from allergic and non-allergic individuals.

Incidence and Remission of Specific IgE Aeroallergen Sensitization from Age of 40 to 60 Years, and Association with Alcohol Consumption

Background: Data on incidence and long-term persistence of IgE aeroallergen sensitization in older adults are limited. Alcohol consumption is a strong immune-modulator with a significant impact on the IgE response. Objectives: We aimed to assess the incidence and remission of aeroallergen sensitization from the age of 40 to 60 years. Furthermore, we examined the relationship of alcohol consumption to the prevalence and incidence of aeroallergen sensitization. Methods: In 1976–1977, a total of 1,200 people born in 1936 and randomly selected from the general population were invited for a health examination (1,052 were examined). At 60 years, they were invited for a re-examination (695 were examined). Stored serum samples from both examinations were analyzed consecutively for serum-specific IgE to aeroallergens by using a qualitative multi-allergen immunoassay. Results: We observed a total of 32 (7.1% of those not sensitized at 40 years) incident cases and 35 (41.1% of those sensitized at 40 years) remittent cases of aeroallergen sensitization over this 20 year period. Persistent as well as incident sensitization was significantly associated with self-reported atopic disease at 60 years. Alcohol consumption (>14 drinks per week) at 40 years was significantly associated with a higher prevalence of sensitization at 40 years, but not with the incidence of sensitization. Conclusions: In older adults, aeroallergen sensitization as reflected by serum-specific IgE positivity to aeroallergens is a dynamic process. Both persistent and incident sensitization was associated with atopic disease. Further studies are needed to clarify the influence of alcohol on the allergen-specific IgE response.