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Aim: Few studies have compared cluster immunotherapy and conventional administration regimens. The aim of this study was to establish the safety profile of these different regimens in patients with allergic respiratory diseases who received index-of-reactivity (IR)-standardized allergen extracts by the subcutaneous route., Materials & Methods: The safety of subcutaneous immunotherapy (SCIT), administered by means of a 4-week cluster titration schedule (cluster-SCIT) or by an 8-week short conventional titration schedule (SC-SCIT), both with a target dose of 8 IR, was assessed in a retrospective, observational, multicenter study., Results: A total of 658 patients (339 cluster-SCIT and 319 SC-SCIT) were recruited from 92 sites in Spain. Injection site reactions occurred in 25.1 and 27.3% of patients treated with cluster-SCIT and SC-SCIT, respectively. Systemic reactions (European Academy of Allergy and Clinical Immunology criteria) were reported for 0.2% of doses and 1.5% of patients with cluster-SCIT, and 0.7% of doses and 4.4% of patients with SC-SCIT. Most reactions were mild and there were no grade 3 or 4 systemic reactions. No life-threatening systemic reactions, anaphylactic shock, or adverse events leading to therapy discontinuation were reported., Conclusion: The safety profile of the cluster regimen supports the use of accelerated SCIT schedules with IR-standardized allergen extracts compared with short conventional schedules, particularly if similar extracts and application methods are used.

Background: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy., Objective: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations., Methods: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur) in 891 patients., Results: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable., Conclusion: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.

Objectives: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations., Methods: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)., Results: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score., Conclusions: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.

Background: The single-blind, placebo controlled oral challenge (SBPCOC) is the definitive way to diagnosis nonsteroidal anti-inflammatory drug (NSAID)-induced reactions., Objective: To evaluate 223 NSAID-sensitive patients by means of SBPCOC, and to describe the main clinical patterns found., Methods: A prospective study was carried out, including 2 patient groups with case histories consistent with NSAID-induced reactions. Of the 223 patients, 174 were diagnosed on the basis of a positive SBPCOC. The second group consisted of 49 patients who were referred because of a documented history of anaphylaxis after taking NSAIDs, and these underwent SBPCOC with potent cyclooxygenase (COX)-1/COX-2 inhibitors, except those reported as being responsible for the reaction. The type of SBPCOC reaction, the NSAID reactivity pattern, and the associated diseases were the main classification criteria., Results: Two broad categories of NSAID-induced reactions were identified: the cross-reactive and selective syndromes. The 150 patients who showed cross-reactive syndromes included 3 types of diseases: type 1, patients with rhinitis and/or asthma who developed nasoocular and/or asthmatic reactions (n=40); type 2, patients with or without chronic urticaria who presented urticaria/angioedema (n=59); and type 3, atopic patients with isolated periorbital angioedema (n=51). In contrast, the selective syndromes, or type 4, included 50 patients who developed anaphylaxis, as well as 11 patients with urticaria during SBPCOC. Finally, a miscellaneous group of reactions not matching any of the above types was identified (n=1 2)., Conclusions: NSAID-sensitive patients can be classified into 4 different groups of reactors, each with well-defined clinical characteristics. Thus, a clinical classification of this NSAID-induced reaction complex is proposed.

Background: The mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced reactions is unknown. However, strong evidence supports the hypothesis of an enhanced production of cysteinyl-leukotrienes. The existence of a polymorphism (A-444C) in the promoter region of the leukotriene (LT)C4-synthase gene (the terminal enzyme in the LTC4 production pathway) has been reported. This polymorphism has yielded contradictory results on its association with aspirin-induced asthma., Objective: The present study was designed to investigate the possible genetic association of C(-444) allele and a specific clinical phenotype of NSAID sensitivity, the NSAID-induced isolated periorbital angioedema, via a case/control study., Methods: The polymorphism A-444C was analyzed in 58 patients with NSAID-induced periorbital angioedema and 61 control subjects, who had undergone single-blind, placebo-controlled oral challenge. Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism., Results: We have not found an association of C(-444), allele with NSAID-induced isolated periorbital angioedema., Conclusions: Further studies are needed to determine whether polymorphisms in the LTC4-synthase gene or other leukotriene-forming enzymes are involved in the pathogenesis of the different subsets of NSAID sensitivity.

Background: Rhinoconjunctivitis and bronchial asthma are atopic diseases with a high prevalence in the Canary Islands (Spain). Given that the most prevalent allergen is the house-dust mite Dermatophagoides pteronyssinus, early detection of genetically susceptible subjects would allow the application of preventive measures. The objective was to investigate the possible association of IL4-R1 (chromosome 5q31-q33) and FcepsilonRI-betaca (chromosome 11q13) markers with the atopic disease in our population., Methods: We performed a case/control study in which patients were recruited on the basis of diagnosis of rhinoconjunctivitis and/or bronchial asthma, and positive skin prick test to D. pteronyssinus. Analysis of IL4-R1 and FcepsilonRI-betaca microsatellites was carried out by PCR and electrophoresis in acrylamide gels., Results: We have not found evidence of association between IL4-R1 and FcepsilonRI-betaca markers and atopic disease in our population. In addition, these markers have shown a high percentage of homozygosis., Conclusions: IL4-R1 and FcepsilonRI-betaca markers have not proved to be useful genetic markers for linkage or association studies in our population.

Background: Atopy is a multifactorial disease, the pathogenesis of which is influenced by both genetic and environmental conditions. Genes in the HLA region have been involved in the control of the IgE response., Objective: In order to investigate whether allergy to house dust mite is associated with HLA in our population, we performed sib-pair analysis in 18 families and a case/control study of 161 non-related individuals., Methods: Levels of total and specific IgE were determined, skin-prick tests were carried out and clinical history was reviewed for every subject in the study. HLA class II typing was performed by the polymerase chain reaction with sequence specific primers., Results: We observed a significant difference from expected values in haplotypes shared by affected sibs; however, the case/control study did not reveal any association with any particular allele., Conclusion: These results suggest that any particular HLA-DRB1/DQA1/DQB1 allele is responsible for the development of allergy to house dust mite in the Spanish population. Some other locus in or close to the HLA region might be involved, e.g., the tumour necrosis factor gene, a possibility that would explain the significant difference from expected values in the segregation of HLA haplotypes.

Food hypersensitivity (FH) is lesser frequent among adult patients than in childhood. Foods implicated in hypersensitivity reactions vary with sociocultural and diet habits from a geographic place to other. We studied 142 adult patients sensitized to foods, among 7698 patients visited at our Outpatient Clinic. Hundred and twenty patients referred clinical symptoms after consumption of one or more foods consistently. From the latest, 107 patients (89.2%) were atopics (92 of them sensitizes to dust mites) and 54 (45%) referred atopic familiar background. Most frequent recorded symptoms were: urticaria/angioedema 84 cases (70%), oral syndrome 65 (54%), asthma 48 (37%) and anaphylaxis 33 patients (27.5%). Shellfish sensitization occurred in 50 patients, fresh fruits in 33 and nuts in 29 cases. Shrimp (48 patients), squid (33), kiwi (14), papaya (14), avocado (13) and banana (12 cases) were the most frequent causes of FH. Significant statistical association between foods and inhalants was observed for fresh fruits and latex (p < 0.001), fresh fruits and pollens (p < 0.01), and shellfish and Blatta germanica (p < 0.001). Prevalence of FH among patients at our Area is around 1.6%. Tropical fruits, as other kind of fruits, seem to share common IgE-epitopes to pollens. High prevalence of shellfish and cockroach hypersensitivity could be more easily developed by previous domestic mites sensitization.

Shellfish is one of the most frequent causes of food allergy. We studied 48 patients (25 male and 23 female) with a mean age of 24.2 +/- 1.8 with shellfish hypersensitivity. A clinical questionnaire was carried out and prick tests were performed using a series of aeroallergens and a battery of extracts of squid, shrimp, lobster, crab, mussel and clam. Prick tests were also performed using raw and boiled extracts from fresh squid, octopus and limpet. Total and specific IgE to these allergens were determined. The most frequent causes of symptoms were shrimp (33 cases) and squid (24 cases). The most frequently found symptoms were Urticaria/angioedema (39 patients), asthma (18 patients) and rhinitis (14 patients). Clinical association was found between Cephalopoedae and Lamelibranquiae (p < 0.05 for clam and p < 0.01 for mussel), but not among both groups and Crustaceans. Association between history and Prick was statistically significant for Crustaceae and Cephalopoedae (p < 0.01) but not for Lamalibranquiae. Association between history and CAP was not found for shellfish. Significant differences among prick-tests with raw and boiled extracts were not found. These results suggest that prick test yields better results than CAP does it, in shellfish hypersensitivity, that clinical association among shellfish hypersensitivity can occurs within the same and different Phylum reflecting common epitopes and that squid, octopus and limpet extracts contain a large amount of heat-stable allergens.