Quality of life in rhinoconjunctivitis assessed with generic and disease-specific questionnaires.

BACKGROUND: Illness as perceived by the allergic patient with asthma and/or rhinoconjunctivitis (RC) can be assessed by measurements of their health-related quality of life (HRQL). For this purpose the RC Quality of Life Questionnaire (RQLQ) has gained general acceptance; however, as most allergic patients experience symptoms from multiple organs, disease-specific HRQL measures may be deficient. This study compares a generic and a disease-specific HRQL instrument in grass and/or mite-allergic patients. METHODS: Two hundred and forty-eight patients with RC and 121 patients with both RC and asthma were studied. Questionnaire information was obtained about allergy-related RQLQ and a generic 15-dimensional instrument for measuring HRQL (15D). Doctors provided general and disease-specific information to classify disease severity according to the global initiative for asthma and allergic rhinitis and its impact on asthma guidelines. RESULTS: Rhinoconjunctivitis patients with persistent moderate-to-severe disease had an impaired quality of life on all items of RQLQ during allergen exposure. The 15D mean score was 0.98 on a day without allergy and 0.83 on a day with allergy (P < 0.001). The correlation between 15D and RQLQ was r = -0.42 on a day with allergy (P < 0.001). Only 15D scores showed statistically significant differences in HRQL between patients with and without asthma. CONCLUSION: During allergen exposure patients with RC experience a serious deterioration in HRQL measured with the disease-specific RQLQ instrument and the generic 15D instrument. The 15D instrument seems to generate a more comprehensive view of the impact of allergen exposure on patient's quality of life than RQLQ.

Molecular basis of allergic cross-reactivity between group 1 major allergens from birch and apple.

Patients allergic to birch pollen often also react with fruits and vegetables, such as apple. The major cause of cross-reactivity between birch and apple is biochemical and immunological similarity between the major allergens, Bet v 1 and Mal d 1, as demonstrated by serological and cellular immunoassays. In addition, birch pollen-specific therapeutic allergy vaccination has been shown to improve allergic symptoms caused by oral ingestion of apple. Detailed analysis of molecular surface areas based on the crystal structure of Bet v 1, and primary sequence alignment, identify potential epitopes for cross-reactive antibodies. Two or more conserved patches are identified when comparing Bet v 1 and Mal d 1, thus providing a molecular model for serological cross-reactivity involving more than one IgE-binding epitope. A minimum of two epitopes would be necessary for cross-linking of receptor bound IgE in functional histamine release assays and skin test. Individual amino acid substitutions, as occurring in isoallergenic variation, may, however, have a dramatic effect on epitope integrity if critical residues are affected. Thus, one area large enough to accommodate antibody-binding epitopes shared by all known Mal d 1 isoallergens and variants is identified, as well as areas shared by Bet v 1 and individual Mal d 1 isoallergens or variants. The occurrence of limited epitope coincidence between Bet v 1 and Mal d 1 is in agreement with the observation that some, but not all, birch pollen allergic patients react with apple, and that the epitope repertoire recognised by the IgE of the individual patients determines the degree of cross-reactivity.

Recombinant allergens/allergen standardization.

Recombinant allergens are genetically engineered isoforms representing allergen molecules from allergen extracts. Immunologic responses of allergic patients toward allergen extracts define the major allergens. For the average allergic patient, the diagnostic sensitivity and treatment efficacy correlate with the concentration of major allergen. Standardization of allergen products (extracts or genetically engineered allergens) can therefore advantageously be performed using a selected recombinant major allergen as a standard. The standardization will furthermore require reagents for which both monospecific, monoclonal, or preferably, recombinant antibodies can be used. Due to differences in the allergenic activity of individual isoallergens and the naturally occurring mixture of isoallergens found in an allergen extract, and due to additional contribution to the allergenic activity from other molecules in the extract, a biologic potency assessment must always be performed as a supplement. This is also the case for a genetically engineered allergen product.

Messages of professional empowerment from the land of Oz.

In the movie adaptation of Baum's book, Dorothy's whole adventure was a dream. But the movie told only a part of the original story. In the print version, Oz was a real place to which Dorothy eventually relocated after 3 more visits; Dorothy moved to Oz permanently in the sixth book (of 13 books) and became a princess. In many ways, critical care professionals are all living in a modern healthcare version of the story of Oz-facing tornadoes, wandering fields of intense expectations, traveling indistinct paths, manipulating wizardly technology, and confronting new enemies. To survive and thrive, we must have brains, heart, and courage. Despite everything that is going on around them, critical care professionals continue to have a sense of mission, a vision of continual improvement and professionalism, and a code of ethics that transcends the complex environment swirling around us. We can begin by creating a personal vision that we wish to achieve. This vision is not an academic exercise but rather a compelling statement that anticipates tomorrow without neglecting today. This vision will require commitment, teamwork, and involvement to make it a reality. Like the end of the original story of Oz, the end of this story is just the beginning. . . . Click your heels together 3 times and say, "It's a new century for critical care nurses!"

Modified T-cell activation pattern during specific immunotherapy (SIT) in cat-allergic patients.

OBJECTIVE: The aim of the study was to analyse early effects of specific immunotherapy (SIT) on immune functions in cat-allergic patients. METHODS: Immunological responses of peripheral blood mononuclear cells from eight cat-allergic patients were analysed before and after SIT in comparison with 11 nonallergic controls. Cells were stimulated in vitro with either bacterial superantigen, mitogen, or cat allergen. Production of IL-12 and TH1/TH2 cytokines was analysed by ELISA and lymphocyte subset distribution was assessed by flow-cytometry. RESULTS: We found a significantly reduced secretion of IL-12 (P < 0.05) from cells of allergic individuals compared with the controls. This finding was associated with significantly lower IFN-gamma production after stimulation with allergen (P < 0.05) that did not increase during SIT. However, no significant differences were seen after stimulation with mitogen indicating an allergen specific IFN-gamma secretion response in allergic individuals. Prior to SIT IL-5 production was significantly higher in cells of allergic donors stimulated with allergen < 0.005 or mitogen (< 0.05). After reaching the maintenance dose for SIT, allergen-induced IL-5 production returned to normal levels, whereas it remained elevated after stimulation with mitogen. These changes were associated with a reduced frequency of CD45 RO T cells following SIT. CONCLUSION: These results suggest that SIT exerts early effects on allergen-specific T-cell responses with selective inhibition of the up-regulated TH2 immune response.

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up.

The long-term effect of tree pollen extract immunotherapy was investigated 6 years after termination of the treatment. Subjective symptom evaluation of 36 patients 6 years after a 3-year period of immunotherapy showed that rhinitis and asthma symptoms remained at the improved level reached just after termination of the treatment. Some 86% of the rhinitis patients and 68% of the asthma patients maintained improvement. None of the rhinitis patients developed asthma in the study period. Skin prick tests reflected the outcome of the subjective symptom assessment. The skin sensitivity of the patients decreased significantly during immunotherapy, and the skin reactions 6 years after specific immunotherapy were still significantly lower than the pretreatment levels. Total IgE and birch-specific IgE levels were constant throughout the study period, and both the affinity and epitope specificity of the IgE antibodies of the patients were the same before, during, and 6 years after treatment. In conclusion, specific immunotherapy reduces symptoms in patients suffering from rhinitis and asthma, and the effect is maintained 6 years after termination of the treatment. Specific immunotherapy seems to prevent long-term development of asthma in rhinitis patients. IgE measurements do not reflect the overall status of the patients.

Comparison of concentrations of Cry j 1 and Cry j 2 in diploid and triploid Japanese cedar (Cryptomeria japonica) pollen extracts.

Japanese cedar (Cryptomeria japonica) possibilities has been a serious allergic disease in Japan. There are two kinds of Japanese cedar trees; the popular one is diploid, the less popular is triploid. These trees are not very different morphologically. However, the relative allergenicity of their pollens is unknown, although both major allergens, Cry j 1 and Cry j 22, have been purified and cloned from the diploid line. Triploid trees are sterile and the allergenicity of their pollen may differ. Using Japanese-cedar-allergic patient sera, we compared the concentration of these two major allergens in both kinds of pollen. Pollen collected from different years and regions was also studied. The results indicate that triploid tree pollen extract has lower concentrations of both major allergens; therefore, the pollen may be less allergenic.

Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity.

To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.

Cow hair allergen (Bos d 2) content in house dust: correlation with sensitization in farmers with cow hair asthma.

Farmers (N = 45) suffering from occupational cow hair asthma were visited at home to evaluate the concentration of cow hair major allergen Bos d 2 in the house dust and to correlate these results with measures of avoidance, degree of sensitization, clinical symptoms, and lung function. Bos d 2 was determined by rocket immunoelectrophoresis. In dust of tiles and linoleum Bos d 2 was difficult to detect, whereas dust samples of carpets often contained high concentrations of the allergen (50-520 micrograms/g fine dust). Bos d 2 levels were significantly higher when barn and living quarters were in the same building. Concentrations of cow hair-specific IgE were correlated with concentrations of Bos d 2 in house dust samples. A concentration of 20-29 micrograms Bos d 2 per gram of house dust could be established as threshold value for relevant IgE sensitization. Avoiding the barn is not a sufficient avoidance measure for cow hair asthmatics if the partner continues cattle farming. Cessation of cattle farming and avoiding the former barn results in a marked reduction in Bos d 2 concentration in living quarters, a decreased degree of sensitization, and a reduced symptom score. Farmers with cow hair asthma should avoid cattle and thoroughly clean all carpets in the living quarters to avoid continuous cow allergen exposure.

X-ray and NMR structure of Bet v 1, the origin of birch pollen allergy.

The three-dimensional structure of the major birch pollen allergen, the 17,500 M(r) acidic protein Bet v 1 (from the birch, Betula verrucosa), is presented as determined both in the crystalline state by X-ray diffraction and in solution by nuclear magnetic resonance (NMR) spectroscopy. This is the first experimentally determined structure of a clinically important inhalant major allergen, estimated to cause allergy in 5-10 million individuals worldwide. The structure shows three regions on the molecular surface predicted to harbour cross-reactive B-cell epitopes which provide a structural basis for the allergic symptoms that birch pollen allergic patients show when they encounter pollens from related trees such as hazel, alder and hornbeam. The structure also shows an unusual feature, a 30 A-long forked cavity that penetrates the entire protein.

[Different threshold concentrations for sensitization by cattle hair allergen Bos d 2 in atopic and non-atopic farmers]. / Differente Schwellenwertkonzen-trationen für Sensibilisierungen durch das Rinderhaarallergen Bos d 2 bei atopischen und nicht-atopischen Landwirten.

Several threshold values for indoor allergens leading to IgE sensitization were proposed. Currently such values exists for allergens of house dust mite, cat, dog, and cockroach and cattle. A high sensitization is known as an important risk factor in the development of asthma. This study was undertaken to examine threshold values of major cow hair allergen Bos d 2 in the house dust of atopic and nonatopic cow hair asthmatic farmers. 45 patients with cow hair asthma were visited at their homes. House dust samples were taken from corridor, living room, and bedroom. The concentration of Bos d 2 was determined by means of rocket immunoelectrophoresis. Additionally, samples of venous blood were taken to demonstrate specific IgE towards cow epithelia by CAP-RAST. Five patients were excluded from further investigations because they have given up their cattle for less than 6 months. In 21 patients occurred typical atopic stigmata like infantil history of atopic eczema, hay fever or milk crust, while the other 19 subjects did not show an atopic diathesis. High sensitization towards cow epithelia (specific IgE > 0.7 kU/l in CAP-RAST) occurred significantly more often in atopics than in nonatopics. In atopic subjects the allergen concentrations leading to IgE sensitization amounted to 1-20 micrograms Bos d 2/g dust, whereas in nonatopics were found higher Bos d 2 threshold values (25-50 micrograms/g dust). The present study suggests that in nonatopic cow hair asthmatics high indoor Bos d 2 levels lead to IgE sensitization as well as the close contact to cattle.