Basophil histamine release, IgE, eosinophil counts, ECP, and EPX are related to the severity of symptoms in seasonal allergic rhinitis

BACKGROUND: Serum specific IgE, basophil histamine release, and blood eosinophil parameters are associated with allergic rhinitis, but investigations of the relationship to the severity of allergic symptoms are few and conflicting. Our study aimed to investigate the seasonal changes in the following laboratory tests: specific IgE, basophil histamine release, eosinophil counts, and serum and plasma eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and to analyze, in detail, the relationship of each individual test to the severity of symptoms in rhinitis patients allergic to both birch and grass pollen. METHODS: The above tests were performed on blood samples obtained from 49 allergic rhinitis patients during the birch-pollen season, during the grass-pollen season, and after the seasons. Symptom-medication diaries were filled in during both pollen seasons. We used partial least square (PLS) analysis to establish an optimal statistical link between the symptom score and medication and the laboratory tests, in an investigator-independent way. RESULTS: Increases in specific IgE, basophil histamine release, eosinophil counts, serum ECP and EPX, and plasma EPX were observed from the birch-pollen season to the grass-pollen season, followed by a decrease from the grass-pollen season to after the pollen seasons, except for the specific IgE. No seasonal changes in plasma ECP and total IgE were seen. The PLS analysis found a relationship between symptom score and medication and the aggregate laboratory tests (F-test value 40.2, correlation 0.34 for the cumulative relation). However, the variation in laboratory tests could explain only half of the total variation in symptoms and less than a quarter of the total variation in medication. The symptom score and, to a minor degree, medication were especially correlated with the basophil histamine-release results, with a decreasing relevance of specific IgE, eosinophil counts, total IgE, serum and plasma EPX, and serum ECP. Plasma ECP was not related to the symptom score and medication. CONCLUSIONS: A significant relationship between the severity of allergic rhinitis and various allergic inflammatory markers was found but could account for only a minor part of the variation in the patients' evaluation of their disease.     

Twenty-four-hour time course of eosinophil granule proteins ECP and EPX during bronchial allergen challenges in serum of asthmatic children

To study in vivo monitoring variables for bronchial allergen challenges, we investigated the time course of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein × (EPX) after allergen provocation in serum. Thirty-two asthmatic children sensitive to house-dust mites and six healthy young adult controls were challenged by bronchial allergen provocations with Dermatophagoides pteronyssinus and D. farinae. Blood samples were taken at regular intervals up to 24 h. Base-line concentrations of ECP ( P <0.004), EPX ( P <0.002), and eosinophils ( P <0.001) were found to be increased in asthmatic children, as compared with healthy controls. ECP and EPX concentrations showed a uniform pattern with two characteristic features: 1) a rapid increase for both mediators up to 30 min after provocation over base-line values ( P <0.0001 and P <0.001), followed by a rapid decrease nearly to base-line values in the next 30 min; and 2) a steady increase for ECP and EPX up to 10 h ( P <0.02 and P <0.01), and even higher levels at 24 h, after challenge ( P <0.002 and P <0.003). We conclude that although eosinophils are activated in asthmatic children after bronchial allergen challenge, ECP and EPX concentrations are not suitable monitoring variables. Base-line eosinophils seem to predict the occurrence of a late-phase asthmatic reaction after allergen provocation.     

Short-term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T-cell responses, in patients with allergic rhinitis

BACKROUND: Birch pollen allergic rhinitis can be sufficiently treated with specific subcutaneous allergoid immunotherapy (IT). However, little is known about the clinical and immunological effects of short-term therapy protocols. OBJECTIVE: To investigate the clinical efficacy of a birch pollen allergoid IT using seven preseasonal injections and to evaluate immunological parameters that might explain clinical findings. METHODS: Thirty-seven patients were included into the study and randomized to either a symptomatic treatment or allergoid IT plus symptomatic treatment. Patients were examined during the pre-IT season, at two extraseasonal visits both before and after IT and during the post-IT season. At each visit, nasal secretion samples were taken and analysed for levels of IL-4, IL-5 and IFNgamma. In addition, short-term birch-specific T-cell lines (TCLs) were cultured from peripheral blood mononuclear cells of 10 patients of the IT group, both before and after IT, and the ratios of lymphocyte subpopulations were determined. Cytokine production by TCLs (IL-4, IL-5, IFNgamma, IL-10) and proliferation of TCLs in response to stimulation with birch pollen allergen were measured. RESULTS: It was possible to evaluate 27 patients in accordance with the study protocol. Clinical symptoms and medication intake were reduced as a result of the IT as were nasal secretion levels of IL-5 (P = 0.007). IFNgamma was increased in nasal secretions (P = 0.01), while IL-4 was not measurable in most samples. No effect was found on proliferation of birch pollen-reactive TCLs, cytokine production by TCLs and the frequency and ratio of CD4+ and CD8bright or CD45RA+ and CD45RO+ cells in peripheral blood (all P > 0.05). Conclusion Preseasonal IT with a birch pollen allergoid is clinically effective in allergic rhinitis and influences cytokine production in the nose, but does not modulate the measured responses of peripheral blood T cells.     

A Double-Blind, Multicenter Immunotherapy Trial in Children, Using a Purified and Standardized Cladosporium herbarum Preparation I. Clinical Results

A double-blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and standardized Cladosporium herbarum allergen preparation. Thirty children with a clinical history suggesting mould-induced asthma and/or rhinoconjunctivitis were included. The diagnosis was confirmed by positive skin prick test and Phadebas RAST as well as positive bronchial and/or conjunctival provocation test to Cladosporium herbarum. Immunotherapy was given for 10 months in a double-blind manner to randomized groups with either Pharmalgen/Cladosporium herbarum preparation or histamine placebo. Allergic side effects to injections were common, especially during the peak of the mould season (July-September in Scandinavia). In the active group, 13/16 patients experienced general reactions during the first 10 months of treatment. After 6 months of treatment, eye, nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups, maybe because most of the children were also sensitive to many other allergens, including Alternaria alternata. However, medication scores were significantly lower in the treated group (P less than 0.01). Bronchial (P less than 0.01) and conjunctival sensitivity (P = 0.01) were significantly reduced in the Cladosporium-treated group but not in the placebo group after 10 months of treatment. This is the first double-blind clinical trial showing the clinical efficacy of immunotherapy in children with mould-induced asthma.