[Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters]. / Inmunoterapia con un extracto oral de Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusiones sobre parámetros in vivo e in vitro.

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.

Inmunoterapia con un extracto oral del Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusines sobre parámetros in vivo e in vitro / Immunotherapy with an oral Alternaria extract in chilhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro

Ante la escasez de trabajos con inmunoterapia oral de Alternaria, planteamos la realización de un ensayo clínico en 39 pacientes, con edades comprendidas entre 7 y 17 años, alérgicos a Alternaria, y sensibilizados también a pólenes y epitelios para evaluar su eficacia clínica y seguridad, así como las repercusiones sobre parámetros in vivo e in vitro. Se empleó un extracto estandarizado, determinando la actividad alérgica mediante RAST inhibición y prick test cutáneo. La cuantificación del alergeno principal (Alt a 1) se llevó a cabo mediante la técnica de fijación en dos lugares, siendo el contenido medio de 34,2 ng Alt a 1/ g de proteína. Los parámetros analizados fueron la puntuación de síntomas-medicación, prick test cutáneo a punto final (TC), test de bronco provocación específico (TBPE), pico de flujo (PF), IgE total y específica e IgG4.Diecinueve pacientes recibieron tratamiento activo con inmunoterapia oral (ITO) y otros diecinueve recibieron tratamiento sintomático. La fase de inicio de la inmunoterapia duró 3 meses, hasta llegar a dosis máxima, que se mantuvo durante 12 meses, alcanzando una dosis acumulada media de 280.000 PNU. Se hallaron diferencias significativas en la disminución de la puntuación de síntomas-medicación en el grupo tratado, tras los 12 meses de inmunoterapia (ITO). No se encontraron diferencias en el grupo control. La inmunoterapia fue bien tolerada, presentando 0,42 reacciones adversas (RA) por 100 dosis administradas, siendo de carácter leve-moderado exclusivamente. Se encontró disminución significativa del tamaño de pápula en el grupo tratado. El TBPE expresado mediante la PD20 mostró cifras significativamente más altas en el grupo con ITO. El pico de flujo no mostró cambios en ninguno de los dos grupos. Los valores de la IgG4 fueron significativamente más altos en el grupo con inmunoterapia. Los niveles de IgE total y específica no mostraron cambios significativos en ambos grupos. En conclusión, la Inmunoterapia Oral con extracto de Alternaria ha demostrado eficacia clínica en pacientes pediátricos, siendo en general bien tolerada, modificando la reactividad específica cutánea y bronquial con incremento de los niveles de IgG4 específica implicados en la respuesta humoral (AU)

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/μg protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response (AU)

Allergens induce apoptosis in lymphocytes from atopic patients.

Repeated stimulation of immune cells may induce an "activation-induced cell death" (AICD) program. Allergy is characterized by the cyclic activation of allergen-reactive immune cells. To study the effects of allergen stimulation in cell proliferation and apoptosis in atopic subjects, peripheral blood mononuclear cells (PBL) from 40 atopic patients with positive reactivity to the allergens Olea Europaea (OE) and Lollium Perenne (LP) (20 without immunotherapy and 20 with specific immunotherapy) and 10 normal subjects were cultured with the allergens OE and LP. PBL from atopic patients proliferate more vigorously than cells from normal subjects after culture in vitro with both allergens, although PBL from atopic subjects without immunotherapy proliferate more than PBL from atopic subjects with immunotherapy. The study of cell proliferation shows that in atopic patients PBL mainly exhibit the CD4/CD45RO phenotype. This preferential proliferation is more evident in PBL from atopic patients treated without immunotherapy. Cell culture with specific allergens induces apoptosis in PBL from atopic patients. The percentage of apoptosis increased when atopic patients had been previously treated with immunotherapy. In addition to the observed increase in cell proliferation, apoptosis mainly occurs in the CD45RO cells that support the involvement of these cells in allergy. Furthermore, results obtained in cells from immunized patients suggest that an AICD process may partly at least explain the mechanism of action of allergen immunotherapy.

Sensitivity to Cupressus: allergenic significance in Córdoba (Spain).

The detection of high levels of Cupressaceae pollen concentration in the air from January to April for several years in our area prompted analysis of the incidence and allergenic significance of sensitivity to this pollen. Furthermore, this is the highest winter-blooming taxa in the city of Córdoba. Skin prick tests were carried out over a one-year period on 1532 patients suffering from respiratory disorders (asthma and/or rhinoconjunctivitis). A total of 42 variables were studied in Cupressus-positive and Cupressus-negative patients; the data obtained were analyzed using a statistical software package. Sensitivity to Cupressus was found in 13% of all outpatients attending the unit, 18% of patients with respiratory disorders and 35% of patients with pollinosis. No significant differences were found between Cupressus-positive (C+) and Cupressus-negative (C-) patients with regard to mean age, sex, patient environment (i.e., rural, semi-rural, urban), personal or family history of atopy, clinical symptoms or evolution after immunotherapy (which did not include this antigen). More C+ patients were found in the higher age brackets (over 25 years old; p < 0.05); C+ patients showed greater duration (p < 0.05) and slower development (p < 0.05) of symptoms, and were also found to be more sensitive to other pollens (p < 0.001). All the Cupressus-sensitive patients also reacted positively to Olea and Fraxinus, compared to 77% and 51% in the two Cupressus-negative groups.

Linear monitoring of patients sensitive to Olea and grass pollens treated with immunotherapy based on glutaraldehyde-modified (allergoid) extracts.

Extracts modified with glutaraldehyde (allergoid) have been offered to allergologists for immunotherapy in the last few years as supposedly clinically effective agents that diminish undesirable side-effects (allergenicity vs. immunogenicity). In order to acquire experience in the use of this therapeutic resource, we monitored a group of patients with pollinosis sensitive to Olea, grass pollens or both, who suffered from seasonal rhinoconjunctivitis (SRC) or rhinoconjunctivitis and seasonal asthma (RCSA) and were administered allergoid treatments standardized in biological units (HEP). The patients were monitored by determination of specific IgE and IgG4, endpoint prick tests and conjunctival provocation tests (CPT) with two types of antigen: Lolium perenne and Olea europaea. Measurements were made at baseline (T1), when the maximal tolerated dose had been given (T2) and 1 year after the treatment was started (T3). According to our results, this type of extract is tolerated quite well and causes no alterations in specific IgG4 or IgE levels. On the other hand, it features significantly decreased allergen-specific skin reactivity and increased response thresholds to the CPT (p < 0.01). A high correlation between skin and conjunctival provocation tests was observed at some stages (r = 0.79, p < 0.01).

IgG4 levels in relation to Olea europaea immunotherapy.

We determined olive pollen-specific IgG4 levels in 100 patients, 39 of whom had been subjected to no immunotherapy (IT) for Olea (31 allergic and 8 nonallergic individuals) and 61 of whom had been administered IT as extracts, including Olea pollen (29 extracts in BUs, 24 allergenic extracts polymerized with glutaraldehyde:Allergoid and 8 extracts standardized in PNUs). IgG4 levels were correlated to the clinical picture, type of extract and average cumulative dose (ACD). We found average IgG4 levels of 0.80 +/- 0.74, 8.60 +/- 13.07 (p < 0.01) and 1.42 +/- 2.5 micrograms/ml (n.s.) for the untreated group and those treated with BU and Allergoid, respectively. The difference between the IT-BU-treated and IT-Allergoid-treated patients was significant at p < 0.01. On the other hand, we found no significant differences among the average IgG4 levels of the three groups in relation to age or sex. The group of asthmatic patients treated with BU extracts had average IgG4 levels of 16 +/- 17.34 micrograms/ml, while those of the rhinoconjunctivitic, non-asthmatic group were 5.05 +/- 6.149 micrograms/ml, with p < 0.05 (Student's "t" test). Thus, patients treated with extracts polymerized with glutaraldehyde had IgG4 levels that were similar to those of the patients subjected to no IT. Also, the group treated with IT extracts standardized in BUs had increased IgG4 levels that were correlated with the cumulative dose, particularly in asthmatic patients.

Monitoring of various types of immunotherapy with gramineal pollens. I. Variation of clinical and biochemical parameters.

We assessed the clinical effectiveness and adverse effect of various types of immunotherapy on 42 pollinotic patients by monitoring their evolution on administration of Perennial lolium specific extract standardized in protein nitrogen units to 14 of them, the same extract but standardized in biological units (BUs) to another 13, and an extract containing four different pollens standardized in BUs to the remaining 15. For this purpose we measured clinical and medicinal scores, liver and kidney biochemical parameters, skin reactions and circulating immunocomplexes (CICs), both before immunotherapy was started (basal levels) and after 3, 6 and 12 month's treatment. We found no significant differences in clinical effectiveness or the occurrence of any adverse effects on administration of the different immunotherapies after one year's monitoring. We did found gradually decreased reactions to the skin tests, which thus provide a reliable means of monitoring allergen-specific immunotherapy.

Monitoring of various types of immunotherapy with gramineal pollens. II. Variation of humoral immunochemical parameters.

We monitored the total and Perennial lolium-specific IgE, IgG, IgM and IgA serum levels of pollinotic patients under three different immunotherapeutic treatments with gramineal pollens over a one-year period. We found statistically significant (p < 0.05) decreases in the total serum IgE levels in successive controls performed after 3, 6 and 12 month's treatment with respect to the basal control levels. The specific IgE levels also decreased gradually throughout the study, while the total serum IgG and IgM levels increased significantly over the first 3 months, and those of IgG continued to increase up to the sixth month. Finally, the total serum IgA levels did not change significantly during the first year of treatment of our pollinotic patients.

Occurrence and clinical profile of the sensitization to Chenopodium in the province of Córdoba (Spain).

The sensitization to pollen from the Amarantaceae and Chenopodiaceae families is responsible for some pollinoses according to various authors. Following an aeropalynological carried out by the Botany Division of our University, we investigated the sensitization to Chenopodium in our pollinic patients in order to establish their clinical patterns. We evaluated 14 variables in Chenopodium-sensitive (CHE +) and nonsensitive (CHE -) patients; the results were analysed by using a computerized statistical programme. Of the 1,000 records reviewed, 38% corresponded to pollinic patients, of whom 8.42% were sensitive to pollen from this family. We found no significant differences between the two groups in the parameters representative of atopic features (e.g. eosinophilia, IgE). However, marked differences were indeed found in the age of appearance of symptoms, frequency of clinical pictures, origin of the patients, duration of the symptoms and evolution upon immunotherapeutic treatment not involving this antigen. These findings endow the sensitization to Chenopodium with special features which should be taken into account in choosing a specific treatment.

[Clinical performance of the basophil degranulation test. Correlation with other diagnostic technics in allergy (II)]. / Rentabilidad clínica del test de degranulación de basófilos. Correlación con otras técnicas diagnósticas en alergia (II).

Although the clinical history is the fundamental method for the diagnosis of reaginic diseases, the use of complementary techniques that gears on the detection of the humoral and cellular effector cells intervening in such affectation is necessary. Thus, we can detect the existence of specific IgE. It can be joined to the basophil membrane by means of techniques "in vivo" as in cutaneous tests, or by means of techniques "in vitro" through cellular techniques in which we apply a biochemical pattern (release of histamine) or a morphological one (HBDT). It can also be free in serum by means of the P-K test or "in vitro" by means of techniques of double antibody. We can also determine, by this last technique, the quantity of the total IgE in serum. In the present work, we review the human basophil degranulation test (HBDT) and its correlation with the prick test, the peripheral blood eosinophilia, the total serum IgE quantification by enzymatic technique and the specific IgE detection by isotope method. In our technique the test was considered positive when the degranulation index with known allergen concentration was greater than 30% for pollens and greater than 25% for D. pteronyssinus with a p less than 0.001. As reported in a previous work, we explain that the normal limits are slightly inferior to those used by some other authors, because in our series, the degranulation average of healthy controls is inferior to that reported by those authors which makes us consider the convenience that the normal limits of degranulation index should be established in a particular way by each technique and allergen.(ABSTRACT TRUNCATED AT 250 WORDS)