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The World Health Organization and various allergy, asthma, and immunology societies throughout the world met on January 27 through 29, 1997, in Geneva, Switzerland to write guidelines for allergen immunotherapy. Over the ensuing year, the editors and panel members reached a consensus about the information to include in the WHO position paper "Allergen immunotherapy: Therapeutic vaccines for allergic diseases." The historical term allergen extract was changed to allergen vaccine to reflect the fact that allergen vaccines are used in medicine as immune modifiers. The document summarizes the scientific literature and rationale for the appropriate use of such therapy to treat allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. It also includes recommendations to improve safety, discusses new techniques being developed that may result in better efficacy and less risk, and offers recommendations for areas of additional and necessary research.

The IUIS Allergen Nomenclature list contains 406 allergens and 192 isoallergens. 329 allergenic molecules should be added if all those reported are classified (data from ww.allergome.org ). The clinical application of all these research products seems not to run in parallel. The aim of the present study is to evaluate how much of the work done by bench-side researchers has been clinically applied. Last 35-years selected papers were classified in ten categories: (a) biochemistry; (b) molecular biology; (c) immunochemistry; (d) basic immunology and genetic; (e) environmental detection; (f) epidemiology; (g) diagnosis; (h) immunotherapy. Papers in categories (a-d) were considered “bench-side” studies, whereas those in categories (e-h) were from the “bed-side”. A single paper may be classified in one or more categories. Within the 4550 selected papers, a bench-side aspect was reported 4767 times, whereas the clinical application of allergenic molecules was studied 1451 times (ratio 3.3/1). Papers were distributed as follows: (a) 1417 (31.1%); (b) 1208 (26.5%); (c) 1725 (37.9%); (d) 417 (9.2%); (e) 851 (18.7%); (f) 135 (3.0%); (g) 446 (9.8%); (h) 46 (1.0%). The analysis of the distribution showed a rise in reporting bench-side studies in the second part of the eighties, with an increase during the last ten years. A rise in the number of papers dealing with the clinical application of allergens is recorded in the late nineties. It seems that there is a historical gap between the isolation, identification, cloning and use in basic research of allergenic molecules, and their application by clinical allergist, even for research purposes only.

Rationale Since data integrity and quality is a basic concern in clinical trials, we examined the validity of an electronic versus paper method of collecting symptom information from subjects. The aim of this study was to determine the correlation between an electronic, interactive voice response system (IVRS) and paper self-assessment measure. Methods Subjects enrolled in an asthma clinical trial investigating a novel treatment were asked to complete a twice daily electronic and validated paper assessment tool. Symptom scores, frequency of beta-2 agonist use, and peak expiratory flow were recorded. For each subject, paired observations were graphed on a scatter plot with a 45 degree reference line. Correlation coefficients of each variable were calculated. Separately, mean difference scores between corresponding observations were evaluated by paired t-tests. Results As a group, the electronic and paper diary scores across subjects were highly correlated (p Conclusions The hypothesis that the mode of data collection (paper versus electronic) has a biasing effect was not supported. Electronic diary data collection (IVRS) appeared appropriate compared to a validated paper and pencil version. Distinct advantages with electronic diaries such as time and date stamping, increased legibility and completeness, and automated database construction are discussed.

Rationale Accuracy and reliability of data collected in allergic rhinitis trials depend on how and when information is recorded by subjects. Methods This was a randomized, 3-week, 3-way, cross-over trial, in 87 adults with allergic rhinitis recording diary data at home, comparing paper (optical mark readable) and electronic (telephone, interactive voice response system, IVRS) tools for: 1) Symptoms recorded during weeks when both or only one instrument was used; 2) Missing data; 3) Ease of use and participant preference. Results Over 40,000 symptoms were recorded by 72 protocol correct subjects. Symptoms recorded during the week that both instruments were used (95% CI difference: −0.13 to 0.22 and −0.13 to 0.18 for morning and evening, respectively) and when the two instruments were used alone (95% CI of difference: −1.05 to 1.60 and −1.45 to 1.32 for morning and evening, respectively) were indistinguishable. 0.45% of paper and 4.12% of IVRS symptoms were missing. Of 10,080 paired symptoms collected on paper and IVRS diaries during the week in which subjects used both, 94.44% were identical. Using IVRS, 63.2% of protocol correct data were entered within the designated time. 85% of subjects preferred the paper instrument, 4% preferred IVRS and 11% had no preference. Conclusions A paper based diary instrument can capture data statistically indistinguishable from data captured by using an electronic product. One other interpretation of these data could be that that the frequency of recording symptoms (twice daily, daily, or weekly) might not have an impact on the outcome of studies to examine treatments of allergic rhinitis.

Rationale Serine proteases have been found to be allergens in venoms from honeybees, bumblebees and paper wasps. Methods The amino acid sequences determined in our laboratory were analyzed by computer techniques; and 3-dimensional structural models were constructed by Swiss-Model with other protease template structures. Results The serine protease domains of all 3 molecules belonged to subfamily S1A Clan PA(S) enzyme S01, trypsin EC 3.4.21.4. All contained the aspartic acid at the bottom of the substrate pocket which binds lysine or arginine, giving a tryptic specificity. The protease domains of Polistes dominulus (Pd) and Apis mellifera (Am) enzymes are 41.5% identical over 248 residues, Pd is 31.8% identical to Bombus pennsylvanicus (Bp) over 245 residues and AM is 33.1% identical to Bp over 242 residues. The 3 enzymes have different residues at the entrance to the substrate binding pocket. Bp has a glycine, which is the most common in this family; Pd has an asparagine, which is uncommon but found in a number of other family members; and Am has a methionine, which is unique. The Am enzyme also has a CUB domain for protein-protein interaction. All three enzymes are active, but their detailed specificity preferences are unknown. They may each have a specialized role in the venom, possibly activation of another component or peptide. Conclusions Although there is some homology in the venom proteases, it does not follow phylogeny; and each enzyme may have a specialized function in the venom.