Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule.

BACKGROUND: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. METHODS: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. RESULTS: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. CONCLUSIONS: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.

Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule

Background: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. Methods: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. Results: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. Conclusions: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy (AU)

Antecedentes: la inmunoterapia sublingual ha sido reconocida como segura y eficaz pero está aún pobremente documentada sobre alergia al polen de árboles. La alergia al aliso, abedul y avellano es importante en los países del norte de Europa, pero su relevancia clínica está aumentando en el sur de Europa. Métodos: 30 pacientes seleccionados y observados a lo largo de una época de polinización, fueron aleatorizados para recibir placebo (15 pacientes) o tratamiento activo (15 pacientes). Completaron el primer año 27 pacientes y 24 de ellos fueron tratados con inmunoterapia activa durante el segundo año del estudio, comparándose con un grupo paralelo tratado solamente con medicamentos. El registro de síntomas y medicamentos durante cada época de polinización, IgE específica al aliso, cambios en la reactividad de la piel, cambio en la prueba de provocación nasal específica y el recuento diario de pólenes de los árboles relevantes fueron considerados para evaluar la eficacia del tratamiento. Resultados: tanto el grupo activo como el placebo mostraron una mejora estadísticamente significativa en los registros, en comparación al año anterior, bajo una menor presión alergénica. La mejoría fue mayor en el grupo activo (76,04 por ciento de reducción de medicamentos) que en el placebo (37,05 por ciento de reducción). En la fase abierta del estudio, los pacientes tratados mostraron una puntuación significativamente mejor que el grupo control. No se registraron cambios significativos en la reactividad de la piel, IgE específica y prueba de provocación nasal específica. La tolerancia del SLIT fue muy buena.Conclusiones: nuestra información muestra un mejor, que no estadísticamente significativo, resultado clínico, en los pacientes tratados con el tratamiento SLIT activo, pero el efecto placebo y la variabilidad de año en año de la carga ambiental alergénica en nuestro pequeño ensayo piloto, no permiten realizar una afirmación concluyente sobre la eficacia de este tipo de terapia (AU)

Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to grasses in children and to Parietaria in adult patients.

BACKGROUND: EPD is the only preventive symptomatic immunotherapy available on the market and approved by competent bodies. Recent double-blind placebo controlled (DBPC) studies have demonstrated its efficacy in seasonal and perennial rhinitis. The aim of the study was to confirm the efficacy and safety of a single dose of immunotherapy administered six-eight weeks before the pollen season. METHODS: Two simultaneous DBPC trials were carried out. The first consisted of 20 children with grass-pollen seasonal rhinitis (Bollate-Milano, Italy) and the second included 30 adult patients with Parietaria-pollen seasonal rhinitis (Genova, Italy). EPD was administered only to the active groups. RESULTS: A significant difference in favour of the active treatment groups was seen in oral antihistamine use (p < 0.05) during the peak pollen seasons. Throughout the pollen seasons, rhinoconjunctivitis scores for the two groups in both studies presented no significant difference, even if the values were lower in the active groups. CONCLUSIONS: The oral antihistamine reduction, observed in the active groups during the seasonal period, supports the efficacy of this treatment, although a significant improvement in the rhinoconjunctivitis symptoms was not observed, probably due to the use of oral antihistamine in the placebo groups. The overall profile of the EPD was good. It could be particularly suited for short term therapy to prevent seasonal symptoms in allergic patients.

Use of antagonist peptides to inhibit in vitro T cell responses to Par j1, the major allergen of Parietaria judaica pollen.

Antigenic peptides with substituted side chains inhibit immune responses to a number of recall Ags from infectious agents in vitro. Here we show that the same strategy can be applied to peptides derived from a pollen protein, the major allergen of Parietaria judaica(Par j1), a plant responsible for most allergenic sensitization in the southern Mediterranean area. Three T cell lines responding to Par j1 protein were used to identify a stimulatory peptide. Two different monosubstituted altered peptide ligands (APL) were identified that bound to the HLA-DR of the responders, did not stimulate the T cell lines on their own, and decreased the response to subsaturating amounts of the unmodified stimulatory peptide. Most important, these APL were able to inhibit the response of these cell lines to intact Par j1 protein. A third monosubstituted peptide bound to the HLA-DR but did not show inhibitory activity. The two APL had a lower affinity than the unsubstituted peptide for the HLA-DR. The last two observations make MHC blockade an unlikely explanation for the observed effect. These results indicate the action of a specific peptide-mediated antagonism that may be useful in controlling the T cell component of an allergic response.

Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.

A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed.

Is the allergen-inhalation challenge predictive of the severity of seasonal asthmatic exacerbations?

Fifteen asthmatic patients sensitized to Parietaria pollen were studied. Before the pollen season they underwent an allergen-inhalation challenge which was preceded and followed by a methacholine-inhalation challenge. Pollen count, symptom score, and drug consumption were monitored daily throughout the study. A severity score was obtained by adding symptom score and drug consumption. Patients underwent a third methacholine challenge during the pollen season, after they had been exposed to a high atmospheric concentration of pollen. The severity score during the first period of the pollen season was significantly correlated with both the early and the late asthmatic responses to the allergen observed before the season (r2 = 0.50; P < 0.005). Bronchial sensitivity to methacholine was significantly increased both after allergen challenge and after seasonal exposure, but these increases correlated neither with each other nor with the severity score. We conclude that bronchial responses to experimental exposure to allergens, but not the changes in nonspecific airway responsiveness, can, in part, predict the severity of asthma exacerbation during the pollen season.

Allergy to pollens from Betulaceae and Corylaceae in a Mediterranean area (Genoa, Italy)--a ten-year retrospective study.

Allergy to pollens from Betulaceae and Corylaceae is becoming a leading problem in Genoa, a northern Mediterranean area in Italy. The results of a 10-year retrospective study on combined observations both on the aerobiological presence of Betulaceae and Corylaceae pollens (Alnus, Corylus, Ostrya) and on the incidence of positive SPT in the allergic population living in the same area are reported. Among 3473 patients suffering from seasonal respiratory allergy with positive SPT to one or more pollens, 558 (16.06%) showed SPT positivity to Betulaceae and/or Corylaceae pollens, both isolated and associated with other allergens. These patients suffered from winter or early spring hay fever, with a high incidence of bronchial asthma. A statistically significant increase (0.02 < p < 0.05) in the number of these sensitizations from 1981 to 1990 has been observed. Some possible explanations for this phenomenon, including an increase in the total amount of local airborne pollens, are suggested. About 24% of the patients with positive SPT to these pollens referred oral allergic syndrome associated with the ingestion of some foods, especially apples and nuts, with or without other additional clinical symptoms.

Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients.

Bronchial provocation tests with aerosol of birch extract were performed before and after pollen season in 11 sensitized subjects. Changes of metacholine bronchial responsiveness and serum-specific IgE level were also assessed. In five patients who did not take steroids to control their symptoms, both early and late asthmatic responses to inhaled allergen were enhanced after season, whereas IgE serum level, but not methacholine sensitivity, was significantly increased. In six patients who needed steroids, neither responses to allergen nor IgE serum level and methacholine sensitivity were significantly changed after season. For the whole group, the increase in immediate bronchial sensitivity to allergen was positively correlated with the increase in specific IgE antibodies. We conclude that seasonal exposure to pollen has, in sensitized patients, a priming effect on bronchial mucosa that may be blunted by steroid treatment. The increased production of specific IgE antibodies appears to be an important mechanism for this priming effect.

Allergy to Parietaria pollen and month of birth.

It has been suggested that the season of birth is a predisposing factor for allergic sensitization. In the last few years many authors in different countries have found a statistically significant correlation between the month of birth and the subsequent allergy for grasses and birch pollens and house dust mites. Nevertheless, other investigators failed to confirm these results. The aim of the present study is to assess the relationship between the season of birth and the development of respiratory allergy to pollen of Parietaria, an Urticacea plant characteristic of Mediterranean flora, which is the most important hay fever producing one in our country. Among the patients who visited the Servizio Autonomo di Allergologia at the St. Martino Hospital (Genoa, Italy) in the year 1986, 264 subjects (113 F and 151 M, 5-35 years of age, all born and living in Genoa and its suburbs) were selected. The birth month of these patients, affected by rhinitis and/or bronchial asthma and with positive prick-test only toward Parietaria pollen, was recorded and compared with that of the population born in Genoa in the same years. Statistical evaluation made by X2 test showed the absence of a statistically significant relationship between the birth in the pollen season (April-July) and the pollinosis, with the exception of the month of May. The reasons of the discrepances observed between the behaviour of Parietaria pollen and that of the other pollens, grasses and birch, described in the above studies, are discussed.