Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study.

BACKGROUND: The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. OBJECTIVE: We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. METHODS: Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. RESULTS: Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). CONCLUSION: Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.

Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial.

BACKGROUND: The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness. OBJECTIVE: The aim of this study was to assess the effects of SLIT on these parameters, in children with Parietaria pollen-induced asthma. METHODS: Thirty children with asthma solely due to Parietaria who participated in a previous randomized, placebo-controlled trial with SLIT were studied: pulmonary function test and methacholine challenge were carried out at baseline in winter 1999 (out season), during the 1999 season (before randomization), and during the 2001 season. RESULTS: Before randomization, there was a significant fall in methacholine provocation concentration during the pollen season vs baseline in both groups (SLIT group 9.78 +/- 5.95 mg/ml vs 3.37 +/- 2.99 mg/ml; placebo 8.70 +/- 6.25 mg/ml vs 2.44 +/- 2.25 mg/ml; P =.005). In the second pollen season, the response to methacholine returned to baseline values in the active group (9.10 +/- 7.7 mg/ml; P = NS vs baseline), whereas in the placebo group a significant increase in reactivity was still present (2.46 +/- 2.26; P = 0.008 vs baseline). No significant difference in FEV(1) and FEF(25-75) between the two groups was observed at all times. CONCLUSIONS: Our data show that SLIT abrogates the seasonal bronchial hyperreactivity in children with asthma due to Parietaria. This may be regarded as an indirect evidence of the effect on bronchial inflammation.

[Indoor allergens in office. Evaluation of the work station]. / Il rischio da allergeni indoor negli uffici. Valutazione delle postazioni di lavoro.

House dust mite and other indoor allergens play a prominent role in the pathogenesis of asthma and other allergic diseases. Several studies have shown a close relationship between sensitisation and/or onset of asthmatic symptoms and levels of indoor allergen exposure. Aim of the study was to investigate the concentration of specific markers of the indoor allergenic pollution, such as Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2. Dust samples were taken using a standard method by means of a 1200 W vacuum cleaner connected with a dust-sampling device (MITEST). A standard A4 size area has been vacuumed four times during 2 min. The concentrations of Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2 were determined in dust samples from 53 different sources (office chair and carpet) using a commercial kit (DUSTSCREEN). House dust mite allergens were not always detectable in the offices. Indoor allergen concentrations (Der p 1, Der f 1, Mite Group 2, Fel d 1) were significant higher in the work station (chair) than in the carpet (p < 0.0001). Der 1 exceeded the current threshold for sensitization in about 1/4 of the samples. Der f 1 was predominant over Der p 1 according to other studies. A good correlation between the results of Der p 1 and Der f 1 was observed both in carpet and work station. Cat allergen was ubiquitous and predominantly detected in the chairs because of the employees' clothes. No appreciable levels for Mite Gr 2 and Bla g 2 were detected. Such an exposure for 8 hours in every working day may be an important occupational risk for the development of sensitization/elicitation symptoms to house dust mite. To reduce mite allergen levels are necessary preventive measure by means of specific techniques and products as barriers for preventing the direct contact with allergens.

Tolerance and effects on skin reactivity to latex of sublingual rush immunotherapy with a latex extract.

BACKGROUND: Specific immunotherapy could be a therapeutic tool for the increasing problem of sensitisation to Natural Rubber Latex (NRL). OBJECTIVE: To investigate the tolerability of SLIT for Latex and its effects on skin reactivity. METHODS: Twenty-six patients (mean age 35.5 years) with an average history of 7.5 years of cutaneous symptoms plus respiratory symptoms (23/26) due to NRL were studied. All underwent rush sublingual therapy (4 days) with a standardized NRL extract followed by a 9-week maintenance treatment. Local and systemic adverse reactions were monitored throughout the treatment. Skin reactivity to NRL extract was evaluated before, during and at the end of the treatment by latex glove-use test, rubbing test and skin prick test. RESULTS: All patients reached the maintenance dose. Out of 1044 administered doses, 257 (24.6%) produced adverse reactions from which 21.4% were local. Only 10.1% of cases required treatment, mainly with antihistamines alone (5.8%), with 2-agonists alone (0.8%) or associated to antihistamines and/or corticosteroids (2.7%). One patient was precautionary treated twice with adrenaline but completed the treatment without further problems. The glove-use test improved significantly after 5 days and 10 weeks of treatment (p = 0.003, p = 0.0004 respectively), whereas the rubbing test improved significantly only after 10 weeks of treatment. Doctor's assessments confirmed the results obtained with the glove-use test (p = 0.003 after 5 days, and p = 0.004 after 10 weeks) but not those obtained with the rubbing test. No change was detected for SPTs. CONCLUSION: SLIT for NRL allergy is able to modify skin reactivity to NRL in days as assessed with methods reproducing HCWs normal exposure to the allergen. Tolerance of SLIT is better than tolerance reported for injective therapy with NRL, but the build up phase should be administered under medical surveillance until sufficient experience has been accumulated. The long-term effect of the treatment deserves further investigation.

Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate.

BACKGROUND: Immunotherapy is a recognized treatment for allergic respiratory diseases. OBJECTIVE: To study the usefulness of immunotherapy in combination with optimal pharmacological therapy. METHODS: Thirty-eight children (8-14 years) suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly controlled by anti-allergic drugs treatment were selected. After randomization according to a double-blind placebo-controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season. RESULTS: Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group. CONCLUSION: The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non-bronchial symptoms.

Variation of the skin end-point in patients treated with sublingual specific immunotherapy.

The reduction in skin reactivity in sensitized subjects is a common finding after injective specific immunotherapy. Few data are, on the contrary, available for sublingual immunotherapy. We assessed the skin reactivity by the end-point titration method in 90 monosensitized subjects (age range 3-50; mean age 19.63) at the baseline and for four consecutive years during the SLIT treatment with two different maintenance regimens. The yearly duration of drug intake was monitored throughout the observation period. Age and skin reactivity to histamine (p < 0.0001; r = 0.871), and age and skin prick end-point (p < 0.0001; r = 0.523) turned out to be statistically positively correlated at baseline. No correlation was on the contrary found between age and the ratio allergen wheal/histamine wheal (p = 0.857; r = -0.019). After 4 years all patients showed at least a significant 4-fold decrease of the skin end-point, whereas 46/90 (51.1%) showed a 16-fold decrease and 29/90 (32.2%) a 64-fold decrease (p < 0.001 in all cases). At the end of the SLIT treatment, 21/90 patients (23.3%) were not using any drug, whereas 16/16 (100%) had given up the use of eye drops, and 34/35 (97%) had given up the use of bronchodilators and bronchial steroids (p < 0.001). After SLIT, 52/90 patients showed a reduction by at least 50% of the yearly duration of drug intake (p < 0.0001). An apparent relationship between the progressively decreasing rate of use of drugs and the decrease in skin reactivity was found, but it did not reach the point of statistical significance (p = 0.081). Patients treated with the daily allergen administration schedule, in spite of a lower cumulative dosage, showed a significantly greater decrease in skin reactivity (p < 0.001) and a higher rate of both no use of any drug (p = 0.013) and of at least a 50% reduction of the yearly duration of drug intake (p = 0.001) as compared to patients treated with three allergen administrations per week.

Mite antigens enhance ICAM-1 and induce VCAM-1 expression on human umbilical vein endothelium.

Although sublingual allergen-specific immunotherapy has been proved to be effective in the treatment of allergic diseases, controversy surrounds the means by which such a local therapy can induce systemic immunological changes. Adhesion molecules are critical in the regulation of leukocyte traffic. It has been hypothesized that allergenic extract, administered locally, may induce an up-regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in local recruitment of circulating inflammatory cells. In the present study we investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM expression of human endothelial cells (HEC). To do this, slices of whole human umbilical cord vein underwent short-term (8 hours) cultures in the presence or absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of the specimens were then evaluated immunohistochemically for expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) molecules. The results revealed that while Der p1 is capable of significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although preliminary, these results clearly support the hypothesis that at least some of the effects of sublingual immunotherapy may derive from inflammatory cell recruitment at the site of allergen release.

Mite antigens enhance ICAM-1 and induce VCAM-1 expression on Human Umbilical Vein Endothelium

Although sublingual allergen-specific immunotherapy has been proved to be effective in the treatment of allergic diseases, controversy surrounds the means by which such a local therapy can induce systemic immunological changes. Adhesion molecules are critical in the regulation of leukocyte traffic. It has been hypothesized that allergenic extract, administered locally, may induce an up-regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in local recruitment of circulating inflammatory cells. In the present study we investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM expression of human endothelial cells (HEC). To do this, slices of whole human umbilical cord vein underwent short-term (8 hours) cultures in the presence or absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of the specimens were then evaluated immunohistochemically for expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) molecules. The results revealed that while Der p1 is capable of significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although preliminary, these results clearly support the hypothesis that at least some of the effects of sublingual immunotherapy may derive from inflammatory cell recruitment at the site of allergen release (AU)

Aunque se ha demostrado que la inmunoterapia sublingual con alergeno específico (ITSA) es eficaz en el tratamiento de enfermedades alérgicas, se discute cómo un tratamiento local puede inducir modificaciones inmunitarias sistémicas. Las moléculas de adhesión son esenciales en la regulación leucocitaria, y se ha planteado la hipótesis de que el extracto alergénico, administrado localmente, puede inducir una estimulación de las moléculas de adhesión vascular (CAM) de los vasos de la mucosa, que se traduce en un reclutamiento local de células inflamatorias circulantes. En el presente trabajo hemos investigado si los antígenos de ácaros Der p1 y Der p2 pueden regular la expresión de células endoteliales humanas (CEH) por CAM. Para ello, se sometió a cortes de vena de cordón umbilical humano completo a cultivos a corto plazo (8 horas) en presencia o en ausencia del antígeno de ácaro (controles no estimulados basales). Después se evaluó inmunohistoquímicamente la expresión de moléculas ICAM-1 y VCAM-1 en cortes criostáticos de las muestras. Este análisis reveló que Der p1 es capaz de regular significativamente ICAM-1 y VCAM-1 sobre CEH, mientras que el antígeno Der p2 regula moderadamente la expresión de ICAM-1 pero es ineficaz para regular VCAM-1. Un que preliminares, estos resultados apoyan conclaridad la hipótesis de que al menos parte de los efectos de la inmunoterapia sublingual pueden deberse al reclutamiento de células inflamatorias en el lugar de liberación del alergeno (AU)

A pre-seasonal birch/hazel sublingual immunotherapy can improve the outcome of grass pollen injective treatment in bisensitized individuals. A case-referent, two-year controlled study.

BACKGROUND: The study tests the hypothesis of a reduction of priming due to tree allergy in patients sensitised to both birch/hazel and grass pollen undergoing an associated preseasonal Sublingual/Injective immunotherapy. METHODS: 36 out of 49 bisensitized candidates were pair-matched into 18 case-referent couples. During two years all patients were administered preseasonal grass-SIT and one patient in each couple received also birch/hazel-SLIT. Diary cards were fulfilled for three consecutive grass pollen seasons. Specific Nasal Provocation Test (NPT) for grass and aspecific bronchial challenge were done; sera were analyzed for specific IgE and IgG. RESULTS: During the peak of the grass pollen season both groups showed a significant improvement in total symptom-score. Conjunctivitis and cough improved significantly more in patients with associated therapies. While antihistamine score decreased significantly in both groups, antiasthmatics did only in the SLIT-SIT group. The follow-up documented a significant increase in grass- and birch-specific IgG and a decrease in grass-specific IgE. Grass-NPT threshold was clearly higher in SLIT-SIT-group (p = 0.01) and only in this group PD20 methacholine improved significantly (p < 0.05). CONCLUSIONS: Combined birch/hazel-SLIT and grass-SIT are safe and improve clinical outcomes of SIT alone in young bisensitized patients. Priming reduction is supported by specific NPT and bronchial hyperresponsiveness.

Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.

BACKGROUND: Subcutaneous immunotherapy for respiratory allergy has shown a long-lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used. OBJECTIVE: We aimed to evaluate whether a long-lasting effect of SLIT occurs, in a prospective parallel group controlled study. METHODS: Sixty children (mean age 8.5 years) suffering from allergic asthma/rhinitis due to mites were subdivided into two matched groups: 35 underwent a 4- to 5-year course of SLIT with standardized extract and 25 received only drug therapy. The patients were evaluated at three time points (baseline, end of SLIT and 4 to 5 years after SLIT discontinuation) regarding presence of asthma, use of anti-asthma drugs, skin prick tests and specific IgE. RESULTS: We found that in the SLIT group there was a significant difference vs. baseline for the presence of asthma (P

True multifood allergy in a 4-year-old child: a case study.

BACKGROUND: Food allergy is quite common in children, but it usually trends to improve with ageing. When an individual has specific IgE to a large variety of foods (multifood allergy) the clinical picture may be of remarkable severity and the avoidance of the offending foods may lead to severe dietary impairment. We describe a case of a child with ascertained multifood allergy. METHODS: The prick-by-prick testing with fresh foods and serum IgE tests were used to evaluate the patient's sensitivity to food allergens. The clinical effect of sensitizations were evaluated by DBPCFC which was carried out for egg, fish, peanuts, walnut, fig, asparagus, orange, chicory, medlar, peach, strawberry and cherry. Each challenge was performed on a separate day. Medical assistance and resuscitation facilities were available during the whole challenge procedures. RESULTS: SPT with fresh food gave a 4 mm wheal for fig, asparagus, cherry and walnut; a 5 mm wheal for medlar and orange; a 6 mm wheal for chicory and strawberry; a 7 mm wheal for fish and peanuts; an 8 mm wheal for peach and a 9 mm wheal for egg. The RAST assay confirmed the presence of specific IgE to egg, fish, peanuts, walnut, fig, orange, strawberry, peach, and cherry. The total serum IgE was 730,6 kU/l.The DBPCFC was positive, at various degrees, for all foods tested according to skin sensitizations. CONCLUSIONS: The case herein described is a true multifood allergy, as confirmed by the DBPCFC. Multifood allergy is not common, but when present it can lead to severe dietary limitation.

True multifood allergy in a 4-year-old child: a case study

Background: Food allergy is quite common in children, but it usually trends to improve with ageing. When an individual has specific IgE to a large variety of foods (multifood allergy) the clinical picture may be of remarkable severity and the avoidance of the offending foods may lead to severe dietary impairment. We describe a case of a child with ascertained multifood allergy. Methods: The prick-by-prick testing with fresh foods and serum IgE tests were used to evaluate the patient's sensitivity to food allergens. The clinical effect of sensitizations were evaluated by DBPCFC which was carried out for egg, fish, peanuts, walnut, fig, asparagus, orange, chicory, medlar, peach, strawberry and cherry. Each challenge was performed on a separate day. Medical assistance and resuscitation facilities were available during the whole challenge procedures. Results: SPT with fresh food gave a 4 mm wheal for fig, asparagus, cherry and walnut; a 5 mm wheal for medlar and orange; a 6 mm wheal for chicory and strawberry; a 7 mm wheal for fish and peanuts; an 8 mm wheal for peach and a 9 mm wheal for egg. The RAST assay confirmed the presence of specific IgE to egg, fish, peanuts, walnut, fig, orange, strawberry, peach, and cherry. The total serum IgE was 730,6 kU/l. The DBPCFC was positive, at various degrees, for all foods tested according to skin sensitizations. Conclusions: The case herein described is a true multifood allergy, as confirmed by the DBPCFC. Multifood allergy is not common, but when present it can lead to severe dietary limitation (AU)

Antecedentes: La alergia a alimentos es muy común en niños y tiende a mejorar con la edad. Cuando un individuo presenta IgE específica frente a una gran variedad de alimentos (alergia alimentaria múltiple), su cuadro clínico puede ser de gravedad notable y el evitar los alimentos responsables de esa alergia, puede generar problemas dietéticos. En este estudio, se describe el caso de un niño con alergia alimentaria múltiple establecida. Métodos: Para evaluar la sensibilidad del paciente a alergenos de alimentos, se utilizó la prueba prick-prick con alimentos frescos y además, los valores de IgE en suero. La respuesta clínica a las sensibilizaciones, se evaluó por PPDCCP, el cual se llevó a cabo con huevo, pescado, cacahuete, nuez, higo, espárrago, naranja, escarola, níspero, melocotón, fresa y cereza. Cada prueba se realizó en un día diferente y, se dispuso siempre de asistencia médica y medidas de resucitación cardio-respiratoria. Resultados: El SPT con alimentos frescos, dio una pápula de 4 mm para higo, espárrago, cereza y nuez; de 5 mm, para níspero, y naranja; de 6 mm para escarola y fresa; de 7 mm para pescado y cacahuete; de 8 mm para melocotón y de 9 mm para huevo. El análisis de RAST confirmó la presencia de IgE específica frente a huevo, pescado, cacahuete, nuez, higo, naranja, fresa, melocotón y cereza. El resultado de IgE total en suero fue de 730,6 kU/l.El PPDCCP fue positivo, a varios niveles, para todos los alimentos probados en relación a las sensibilizaciones cutáneas. Conclusiones: El caso descrito en este artículo, es una alergia alimentaria múltiple como se confirmó por el PPDCCP. La alergia alimentaria múltiple, no es muy común, pero cuando se presenta, conlleva limitaciones importantes en la dieta (AU)

Clustered schedules in allergen-specific immunotherapy.

BACKGROUND: Injective immunotherapy is traditionally performed with a build-up phase lasting 3 to 4 months. The costs, decreasing compliance from both patients and clinicians and inconveniences due to this schedule may be overcome using different schedules. METHODS AND RESULTS: A revision of the published papers with clustered schedules has been made. Attention has been focussed on tolerance and its relationships with relevant parameters such as kind of extract (aqueous or depot), allergens and their pharmaceutical presentation, schedule followed, use or not of a premedication, clinical manifestations of patients before treatment. For a better revision, papers dealing with clustered schedules have been divided into two groups. The first group includes 20 papers not designed to study the clustered schedule but using it to study other parameters affected by specific immunotherapy. The second group includes 9 papers specifically or mainly designed to study the clustered schedule. A huge difference in the rate of side effects could be assessed among different papers, even in studies run with similar allergens from the same producer and with a similar schedule. CONCLUSIONS: Summarizing the results of the revision, the following conditions seem to lead to the optimal tolerance of the clustered schedule: use of a premedication; use of a depot preparation; use of no more than 4 administrations per cluster; administration of 1-2 clusters per week and of 4 to 6 clusters in total. These results seem promising but further efforts are required to better define the optimal clustered schedule.

Clustered schedules in allergen-specific immunotherapy

Background: Injective immunotherapy is traditionally performed with a build-up phase lasting 3 to 4 months. The costs, decreasing compliance from both patients and clinicians and inconveniences due to this schedule may be overcome using different schedules. Methods and results: A revision of the published papers with clustered schedules has been made. Attention has been focussed on tolerance and its relationships with relevant parameters such as kind of extract (aqueous or depot), allergens and their pharmaceutical presentation, schedule followed, use or not of a premedication, clinical manifestations of patients before treatment. For a better revision, papers dealing with clustered schedules have been divided into two groups. The first group includes 20 papers not designed to study the clustered schedule but using it to study other parameters affected by specific immunotherapy. The second group includes 9 papers specifically or mainly designed to study the clustered schedule. A huge difference in the rate of side effects could be assessed among different papers, even in studies run with similar allergens from the same producer and with a similar schedule. Conclusions: Summarizing the results of the revision, the following conditions seem to lead to the optimal tolerance of the clustered schedule: use of a premedication; use of a depot preparation; use of no more than 4 administrations per cluster; administration of 1-2 clusters per week and of 4 to 6 clusters in total. These results seem promising but further efforts are required to better define the optimal clustered schedule (AU)

Introducción: La inmunoterapia subcutánea conlleva una fase de incremento de dosis que dura de 3 a4 meses. El coste, la baja aceptación tanto de pacientes como de médicos y los inconvenientes debidos a este esquema convencional, pueden verse mejorados siguiendo pautas alternativas de tratamiento. Método y resultados: Se ha realizado una revisión de los trabajos publicados siguiendo esquemas cluster. La atención se ha centrado en la tolerancia y su relación con parámetros relevantes tales como tipo de extracto (acuoso o depot), alergenos y sus presentaciones farmacéuticas, pauta empleada, uso o no de premedicación y diagnóstico clínico de los pacientes estudiados. Para una revisión mejor, los tra-bajos que siguen pautas cluster han sido divididos en 2 grupos. El primer grupo incluye 20 trabajos no enfocados para el estudio de esquemas cluster sino para valorar otros parámetros relacionados con la inmunoterapia específica. El segundo grupo incluye 9 trabajos diseñados específicamente para estudiar pautas cluster. Se ha observado una gran variabilidad en la tasa de efectos adversos entre los diferentes trabajos, incluso en aquellos estudios desarrollados con alergenos similares producidos por un mismo fabricante y con una pauta similar. Conclusiones: Parece observarse que hay unos determinados factores que podrían influir en la tolerancia óptima de pautas cluster: uso de premedicación; empleo de extractos depot; administración inferior a 4 inyecciones por visita-cluster, pautas cluster con administraciones no superiores a 2 visitas por semana y de 4 a 6 visitas-cluster en total. Estos resultados parecen prometedores, pero se requiere más información para poder definir una pauta de cluster óptima (AU)

CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation.

BACKGROUND: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. METHOD: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. RESULTS: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). CONCLUSIONS: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation.

CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation

Background: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. Method: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. Results: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). Conclusions: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation (AU)

Antecedentes: Existen datos convincentes de que las células precursoras hematopoyéticas (HPC) desempeñan una función esencial en el establecimiento de la inflamación celular en las enfermedades alérgicas. Se han descrito a menudo mayores concentraciones de CD34+ HPC circulantes, comprometidas con la estirpe mieloide, en la rinitis alérgica, el asma y el eccema, mientras que se han identificado células CD34+ en los infiltrados celulares de tejidos, en zonas periféricas de inflamación. Método: Realizamos un estudio preliminar para evaluar el tráfico de CD34+ en la sangre periférica de 22 pacientes consecutivos (13 varones y 9 mujeres; promedio de edad de 28,9 años), con independencia del tratamiento. Los pacientes padecían rinitis, asma, eccema, urticaria y reacciones alimentarias adversas de presunto origen alérgico. Las reacciones alérgicas eran extrínsecas en 18 pacientes e intrínsecas en cuatro. En el caso de 12 pacientes que recibieron inmunoterapia específica por vía sublingual se cuantificaron las células CD 34 + en el momento de inscripción (T0), un año después (T1) y dos años más tarde (T2). La intensidad de los síntomas se graduó con una escala de cinco puntos (0 = ausencia de síntomas y 4 = síntomas graves). Se evaluó como testigos a 20 personas sanas (10 varones y 10 mujeres; promedio de edad de 24,5 años).Para obtener información sobre la cantidad de HPC circulantes, con independencia del compromiso de estirpe (Lin ñ ) y el grado de diferenciación (CD34bright/dim: no divididas/divididas), aplicamos una modificación del protocolo de Milán para calcular las células CD34+ en sangre periférica. Las células se analizaron empleando un BD FACScan o un FACSCalibur y los resultados se expresaron como porcentaje de células positivas. Resultados: El tráfico de células CD 34 + en el grupo de control fue muy escaso, pues todos los valores fueron t = 0,000].Conclusiones: Los datos descritos indican que el método empleado es eficaz para evaluar la inflamación alérgica aguda, así como la inflamación persistente mínima que subyace a una enfermedad clínica asintomática. La evaluación del tráfico periférico de CD34bright/dim, si lo confirman los resultados de un estudio multicéntrico que se está planificando junto con un estudio tradicional de la IgE circulante, podría ser un método de laboratorio incruento fidedigno para vigilar la inflamación alérgica. (AU)

An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants.

BACKGROUND: About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux (GER) and 1/3 of them also show Cow's Milk Allergy (CMA) symptoms. METHODS: We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow's Milk Formula (eHF) in infants suffering from GER. Ten infants showing GER symptoms and 10 normal babies, all fed with breast-milk substitutes, were enrolled. Clinical symptom scores related to GER were assessed for one week. The Gastric Emptying Time (GET) was determined by means of dynamic echography after feeding with cow's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms. RESULTS: All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects (205 vs 124 min, p = 0.000). Switching to the eHF led to a significant clinical improvement (p = 0.0039) especially in babies skin-test and RAST positive to cow's milk, and to a significant decrease toward the normal value of the GET (167 min, p < 0.001). CONCLUSIONS: The eHF tested improves GER symptoms in infants suffering from this disease. Our experience confirms and supports the use of dynamic echography as a reliable, simple, and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER.

An extensively hydrolysed cow's milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants

Background: About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux (GER) and 1/3 of them also show Cow's Milk Allergy (CMA) symptoms. Methods: We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow's Milk Formula (eHF) in infants suffering from GER. Ten infants showing GER symptoms and 10 normal babies, all fed with breast-milk substitutes, were enrolled. Clinical symptom scores related to GER were assessed for one week. The Gastric Emptying Time (GET) was determined by means of dynamic echography after feeding with cow's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms. Results: All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects (205 vs 124 min, p = 0.000). Switching to the eHF led to a significant clinical improvement (p = 0.0039) especially in babies skin-test and RAST positive to cow's milk, and to a significant decrease toward the normal value of the GET (167 min, p < 0.001). Conclusions: The eHF tested improves GER symptoms in infants suffering from this disease. Our experience confirms and supports the use of dynamic echography as a reliable, simple, and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER (AU)

Antecedentes: Alrededor del 20 por ciento de los niños alimentados con sustitutivos de leche materna padecen reflujo gastroesogáfico (GER) y un tercio de ellos además muestran síntomas de alergia a la leche de vaca (CMA). El estudio fue diseñado para, mediante ecografía dinámica, evaluar la utilidad de la fórmula de leche de vaca ampliamente hidrolizada (eHF) en niños que padecen GER. Métodos: Fueron reclutados 10 pacientes que mostraban síntomas de GER y 10 bebés normales, todos ellos alimentados con sustitutivos de leche materna. Los valores de síntomas clínicos relacionados con el GER fueron evaluados durante una semana. El tiempo de vaciamiento gástrico (GET) fue determinado mediante ecografía dinámica después de alimentar con fórmula derivada de leche de vaca a pacientes que mostraban previamente GER, y otra vez después de una semana, en pacientes alimentados con eHF. Resultados: Todos los niños con diagnóstico clínico de GER mostraron un nivel anormalmente alto de GET en comparación con los niños normales (205 vs 124 min, p = 0,000). El cambio a la alimentación con eHF indujo a una mejora clínicamente significativa (p = 0,0039) especialmente en bebés con pruebas cutáneas y RAST positivo a leche de vaca y un descenso significativo a valores normales del GET (167 min, p < 0,001).Conclusiones: El eHF estudiado mejora los síntomas de GER en niños que padecen dicha enfermedad. Nuestra experiencia confirma y apoya el uso de la ecografía dinámica como un método de diagnóstico fidedigno, simple y no invasivo para niños con un aumento del GET asociado a síntomas clínicos del GER (AU)