Ana Isabel Tabar

Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis

BACKGROUND The efficacy and safety of the 300-index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults. OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis. METHODS In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5-17 years of age) with grass pollen-related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety. RESULTS The intent-to-treat population included 266 children (mean age, 10.9 +/- 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group (P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season (P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported. CONCLUSION Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis.

Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract.

Background:  Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein.

Component-resolved diagnosis of pollen allergy based on skin testing with profilin, polcalcin and lipid transfer protein pan-allergens

Background Allergy diagnosis needs to be improved in patients suffering from pollen polysensitization due to the existence of possible confounding factors in this type of patients.

Three years of specific immunotherapy may be sufficient in house dust mite respiratory allergy

BACKGROUND Specific immunotherapy (SIT) duration for respiratory allergy is currently based on individual decisions. OBJECTIVE To evaluate the differences in clinical efficacy of SIT as a result of the duration between the current recommended limits (3-5 years). METHODS A 5-year prospective, controlled clinical trial of SIT blind until the first year and randomization to a 3-year (IT3) or 5-year (IT5) course was conducted. Of the 239 patients with respiratory allergy caused by D pteronyssinus initially included, 142 completed 3 years of SIT with good compliance. Twenty-seven controls were included at the third year. Efficacy of SIT after 3 (T3) and 5 (T5) years was assessed by using clinical scores, visual analog scales (VASs), rhinitis (RQLQ) and asthma (AQLQ) quality of life questionnaires, skin tests, and serum immunoglobulins. RESULTS At T3, significant reductions were observed in rhinitis (44% in IT3 and 50% in IT5; P < .001), asthma (80.9 % in IT3 and 70.9% in IT5; P < .001) scores, VAS (P < .001 in both), RQLQ (P < .001 in both) and AQLQ (P < .001 in both). At T5, the clinical benefit was maintained in both groups, and IT5 patients presented additional decreases (19%; P = .019) in rhinitis scores. At Tf, specific IgG(4) measurements were lower in IT3 (P = .03) without detecting differences in IT5. An increase in asthma score of 133% was the only difference observed in controls. CONCLUSION Clinical improvement is obtained with 3 years of D pteronyssinus SIT. Two additional years of SIT add clinical benefit in rhinitis only.

Differences among Pollen-Allergic Patients with and without Plant Food Allergy

Background: A considerable number of pollen-allergic patients develops allergy to plant foods, which has been attributed to cross-reactivity between food and pollen allergens. The aim of this study was to analyze the differences among pollen-allergic patients with and without plant food allergy. Methods: Eight hundred and six patients were recruited from 8 different hospitals. Each clinical research group included 100 patients (50 plant food-allergic patients and 50 pollen-allergic patients). Diagnosis of pollen allergy was based on typical case history of pollen allergy and positive skin prick tests. Diagnosis of plant-food allergy was based on clear history of plant-food allergy, skin prick tests and/or plant-food challenge tests. A panel of 28 purified allergens from pollens and/or plant foods was used to quantify specific IgE (ADVIA-Centaur® platform). Results: Six hundred and sixty eight patients (83%) of the 806 evaluated had pollen allergy: 396 patients with pollen allergy alone and 272 patients with associated food and pollen allergies. A comparison of both groups showed a statistically significant increase in the food and pollen allergy subgroup in frequency of: (1) asthma (47 vs. 59%; p < 0.001); (2) positive skin test results to several pollens: Plantago,Platanus,Artemisia,Betula,Parietaria and Salsola (p < 0.001); (3) sensitization to purified allergens: Pru p 3, profilin, Pla a 1 – Pla a 2, Sal k 1, PR-10 proteins and Len c 1. Conclusion: Results showed relevant and significant differences between both groups of pollen-allergic patients depending on whether or not they suffered from plant-derived food allergy.

Basophil Activation Test and specific IgE measurements using a panel of recombinant natural rubber latex allergens to determine the latex allergen sensitization profile in children.

There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in‐use NRL provocation tests were carried out, as well as specific IgE determination in all patients’ and controls’ sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL‐specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 childrens sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non‐intervened group or those with only one intervention. Specific IgE in sera of children with latex‐fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen‐specific IgE determination could be used as first‐line in vitro diagnostic tests in patients with NRL allergy.

Double‐blind, placebo‐controlled study of Alternaria alternata immunotherapy: Clinical efficacy and safety

Allergen‐specific immunotherapy (ASIT) with fungal extracts has been beset by safety and efficacy problems, which result mainly from qualitative and quantitative variations. Little has been published on the safety and efficacy of these extracts. The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract. A total of 28 patients were selected with rhinitis and/or bronchial asthma because of Alternaria allergy and monosensitization to molds. The patients were randomized to an active ASIT or placebo group, both groups on a conventional immunotherapy schedule (increasing weekly doses until maintenance dose and then monthly doses). Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system. Clinical efficacy was analyzed for a year with symptom/medication diary cards, peak expiratory flow (PEF) measures, clinical severity score, severity of symptoms (visual analog scale), subjective evaluation of treatment by the patient and the physician, and a quality of life questionnaire. Twenty‐three patients completed the study; all reached the established maintenance dose with only two mild adverse reactions in the whole sample. Significant improvements were found after 6 months in respiratory symptoms in the active treatment group, and in all symptoms in both groups. PEF increased significantly in the active treatment group but not in the placebo group. The severity of asthma decreased in the active treatment group, and the severity of rhinitis decreased in both groups. Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group, but only after 12 months in the placebo group. Physicians judged the disease course as significantly better in the active treatment group. ASIT with the A. alternata extract was safe, with clinical improvements after one year of treatment.

Occupational asthma and immunologic responses induced by inhaled carmine among employees at a factory making natural dyes

Carmine is a natural red dye widely used as a food coloring agent and for cosmetic manufacture. It is extracted from the dried females of the insect Dactylopius coccus var. Costa (cochineal). Although it has been reported that inhalation of carmine may give rise to occupational asthma and extrinsic allergic alveolitis, there is little evidence of its immunogenic capacity. We studied nine current employees at a factory making natural dyes and one former employee who had left this plant after occupational asthma developed. A current employee had work-related symptoms of rhinitis and asthma that were confirmed by bronchial provocation tests, and another worker had rhinitis. Immunologic sensitization to carmine and cochineal was evaluated by means of skin testing and determination of serum-specific IgE and IgG subclass antibodies by RAST and ELISA, respectively. The specificity of the RAST assay was investigated by RAST inhibition with different fractions of carmine. The three workers with respiratory symptoms had positive skin prick test reactions to both carmine and cochineal. An immediate response to the bronchial provocation test with carmine and cochineal was observed in the current employee with asthma. Specific IgE antibodies against carmine and cochineal were found only in this worker. RAST inhibition studies indicated that the main allergen had a molecular weight between 10 and 30 kd. Specific IgG antibodies against carmine and cochineal, mainly the subclasses IgG1, IgG3, and IgG4, were found in the 10 subjects surveyed. These findings suggest that carmine may induce immunologic responses, most likely IgE mediated in workers with symptoms of occupational asthma.

Immunopathogenesis of human gastrointestinal infection by Anisakis simplex

BACKGROUND Anisakis simplex is a parasite of fish, and in the case of human infestation, it should be considered as a possible cause of gastrointestinal disease, especially in countries where raw or undercooked fish is a frequent food. Clinical features of anisakiasis may simulate acute abdominal pain, such as that found in patients with gastric ulcers, appendicitis, and Crohns disease. Furthermore, many cases of anisakiasis are diagnosed as eosinophilic gastroenteritis, which is a broad term for a specific disease. OBJECTIVE The purpose of this study was to investigate the immunopathogenesis of human gastrointestinal infestation by A simplex. METHODS Thirteen intestinal biopsy specimens from patients with anisakiasis were analyzed for the presence of messenger (m)RNA for different cytokines and inflammatory mediators by RT-PCR. Specific IgE, eosinophil cationic protein, eosinophil protein X, and tryptase levels were measured in each patients serum. Also, cell cultures were set up with lymphocytes from some patients and stimulated in vitro with Anisakis and Ascaris antigens. RESULTS We performed immunologic phenotyping in 13 patients. All patients underwent biopsy after emergency surgery caused by episodes of acute abdominal pain. In all cases inflammatory infiltrate composed of eosinophils and lymphocytes was found in the intestinal wall. We demonstrated that after infestation, a T(H2)-type immune response occurred. Also, major basic protein, nitric oxide, and eotaxin were found in the tissue, and eosinophil cationic protein and eosinophil protein X levels were elevated in sera. CONCLUSION These data and in vitro lymphocyte cultures indicate that a T(H2) mechanism plays an important role in the inflammatory infiltrate produced by the anchorage of parasites in the gastrointestinal wall.

Respiratory allergy to peach leaves and lipid-transfer proteins

Background Several lipid‐transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3.