Comparison of two diagnostic techniques, skin-prick test and component resolved diagnosis in the follow-up of a cohort of paediatric patients with pollinosis. Multicentre pilot study in a highly exposed allergenic area.

BACKGROUND: Over the last years, different works have been published about the importance of incorporating new diagnosis techniques in allergic patients such as component-resolved diagnosis (CRD). The objective of this study is to compare the evolution of allergic sensitisation profiles by means of CRD and cutaneous tests (SPT) on pollen-allergic patients. METHODS: A total of 123 patients aged between 2 and 14 years were included in an open, prospective, multicentre study. All the children had symptoms suggestive of seasonal respiratory allergic disease, with the diagnosis confirmed by cutaneous tests. Specific-IgE to major pollen-allergens (CRD) and SPT were performed at basal and after three years of follow-up. RESULTS: Out of 123 patients included, a total of 85 were analysed. The mean age was 8±3 years. Significant changes in the allergic sensitisation profiles were observed for the most prevalent allergens (Olea and grass) but it is in grass, the most relevant allergen in terms of allergen pressure, where changes in both absolute and relative frequencies between SPT and CRD were more evident. CONCLUSION: CRD seems to be an essential tool to carry out an appropriate follow-up of patients with allergic respiratory disease, as well as to decide on the immunotherapy composition that best matches the allergic sensitisation profile of patients.

Profilin as a severe food allergen in allergic patients overexposed to grass pollen.

BACKGROUND: Profilins are ubiquitous proteins that act as panallergens in sensitized patients, considered to be mild or incomplete food allergens. The aim of the study was to evaluate the role of profilins as severe food allergens in allergic patients overexposed to grass who were referred for severe food reactions and were sensitized to profilins. METHODS: After a careful in vitro screening, 26 patients were included, classified into two groups, mild (17) and severe reactors (9), based on clinical history and subsequently provoked orally with purified profilin in a double-blind placebo-controlled food challenge setup. RESULTS: A significant number of patients presented severe positive food challenge test reactions at low doses of the allergen profilin. Patients prone to suffer from severe reactions had lower IgG4/IgE ratio to major grass allergens than those who did not. CONCLUSION: Profilins are complete food allergens in food-allergic patient populations that are exposed to high levels of grass pollen. This type of patient constitutes an optimal model to understand the link between respiratory and food allergies. The nature of the observed reactions and the low level of allergen eliciting the reactions suggest that intake through the oral mucosa might constitute a relevant route of exposure to food allergens.

Postmarketing study for assessment of tolerability of a grass allergen immunotherapy tablet (GRAZAX) in patients with rhinitis or rhinoconjunctivitis.

BACKGROUND AND OBJECTIVE: Many patients with grass pollen allergy in Spain have concomitant sensitization to other allergens such as profilin. Since this type of sensitization is more common in Mediterranean countries than in countries where most patients were enrolled in clinical trials on GRAZAX (Phleum pratense 75,000 SQ-T/2, 800 BAU, ALK), the aim of this study was to analyze tolerability to GRAZAX under clinical practice conditions in patients with grass pollen allergy. METHODS: A total of 155 patients were enrolled consecutively in a prospective, open-label, observational study. Adverse reactions were recorded during the first month of treatment at 3 different timepoints: after the first dose, when patients were kept under observation for 30 minutes, and on days 15 and 30 after starting treatment RESULTS: With the first dose, 117 adverse reactions were recorded in 63 patients (40.7%). The commonest reactions (>10% patients) were oral pruritus (25.2%) and throat irritation (24.5%). Ear pruritus was recorded in 7.7%. All reactions but 1 occurred within 30 minutes of administration and all were mild-to-moderate. At the end of treatment, the percentage of patients with adverse reactions had decreased significantly (21.3%). Most adverse reactions (95.2%) were mild-to-moderate and only 3 (1.4%) were severe. No serious adverse reactions were recorded. CONCLUSION: GRAZAX seems to be well tolerated, and most reactions were mild-to-moderate. Many of these reactions occur with the first dose. Therefore, according to the Summary of Product Characteristics, the first dose has to be administered under medical supervision.

Enhanced diagnosis of pollen allergy using specific immunoglobulin E determination to detect major allergens and panallergens.

BACKGROUND: Pollen is one of the main causes of allergic sensitization. It is not easy to make an etiological diagnosis of pollen-allergic patients because of the wide variety of sensitizing pollens, association with food allergy, and increasing incidence of polysensitization, which may result from the presence of allergens that are common to different species, as is the case of panallergens. OBJECTIVE: To compare the results of skin prick tests (SPT) using whole pollen extract with specific immunoglobulin (Ig) E determination for several allergens (purified panallergens included) in the diagnosis of polysensitized pollen-allergic patients. METHODS: The study sample comprised 179 pollen-sensitized patients who underwent SPT with pollen extract and allergen-specific IgE determination against different allergens. RESULTS: The level of concordance between the traditional diagnostic test (SPT) and IgE determination was low, especially in patients sensitized to the panallergens profilin and polcalcin. In the case of SPT, the results demonstrated that patients who are sensitized to either of these panallergens present a significantly higher number of positive results than patients who are not. However, IgE determination revealed that while patients sensitized to polcalcins are sensitized to allergens from a higher number of pollens than the rest of the sample, this is not the case in patients sensitized to profilins. On the other hand, sensitization to profilin or lipid transfer proteins was clearly associated with food allergy. CONCLUSIONS: Sensitization to panallergens could be a confounding factor in the diagnosis of polysensitized pollen-allergic patients as well as a marker for food allergy. However, more studies are required to further investigate the role of these molecules.

Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study.

BACKGROUND: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. OBJECTIVE: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. METHODS: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur) in 891 patients. RESULTS: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. CONCLUSION: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.

Tolerance of a Salsola kali extract standardized in biological units administered by subcutaneous route. Multicenter study.

BACKGROUND: Sensitivity to Salsola kali is a frequent cause of allergic respiratory disease in various regions of Spain. However, there are very few articles in which this allergen has been studied. METHODS AND RESULTS: In order to evaluate the tolerance of this extract, a prospective study has been performed. This study was observational, multi-centred and open, involving 88 patients with allergic respiratory disease due to sensitivity to Salsola, aged between 5 and 52 years. The administration of the extract was performed subcutaneously, through one of two treatment schedules: cluster (8 doses in 4 visits) or conventional (13 doses in 12 visits). A total of 42 adverse reactions were registered, in 26 patients (35 local reactions in 21 patients and 7 systemic reactions in 6 patients). Among the 7 systemic reactions, 4 were registered with the cluster protocol and 2 with the conventional protocol (p = 0.329). In no patients were serious adverse reactions registered. CONCLUSION: The subcutaneous administration of a Salsola extract is safe and well tolerated, both when administered using a conventional schedule and when using a cluster schedule.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

Immunotherapy with an extract of Olea europaea quantified in mass units. Evaluation of the safety and efficacy after one year of treatment.

Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and bronchial asthma (BA) in the region of Jaén (southern Spain), where this allergen reaches atmospheric levels of almost 7000 grains/m3 during pollen season (May and June) and produces high morbidity. Specific immunotherapy (SIT) has proven very efficient in allergic RC and BA caused by grass pollen. Considering the availability of a biologically standardized extract of Olea europaea, with its major allergen quantified in mass units, we decided to investigate SIT with this extract in a group of rhinitic and/or asthmatic patients monosensitized to olive. We studied tolerance, safety, and efficacy by comparison of the active group (subjected to SIT) with a control group that did not receive SIT. A hyposensitizing dose of Olea europaea extract was administered preseasonally, establishing a maintenance dose 3.8 times higher than those administered in conventional treatments. Eighty-three percent of the patients reached the proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate of 0.8% of systemic reactions. A significant decrease in cutaneous (p < 0.001) and bronchial (p < 0.001) reactivity was observed in the active group, but not in the control group. Also, a decrease in specific IgE and an increase in IgG1 and IgG4 were found in the group of patients treated with SIT. Regarding clinical evolution, the active group, but not the control group, experienced a clear statistically significant improvement both in nasal (p < 0.05) and bronchial (p < 0.05) symptoms, in addition to a significant decrease in the consumption of antihistamines (p < 0.05) and beta 2-agonists (p < 0.01). In conclusion, SIT with olive extract proved to be safe and efficacious for the treatment of asthma and rhinitis caused by this allergen.

[Pre and post-operative autotransfusion. A comparative study of hematology, biochemistry and red cell metabolism in pre-donated blood and blood from post-operative surgical drainage]. / Autotransfusión pre y postoperatoria. Estudio comparativo de la hematología, bioquímica y metabolismo eritrocitario en sangre predonada y sangre de drenaje postoperatorio.

PURPOSE: The widespread use of aggressive surgical procedures, along with the increasing incidence of traffic accidents, has raised the necessity of homologous blood beyond the supplies of blood banks. This fact, plus the risks of homologous transfusion and the costs of blood bank maintenance, has prompted the advance of blood saving procedures such as autotransfusion, both in the pre-deposit (preoperative autotransfusion, POA) and the surgical drainage reinfusion (postoperative autotransfusion, SDR) modalities. As there is some controversy about the use of one or the other of the above procedures, the purposes of this study were: 1) to analyse the haematological and biochemical characteristics of blood, both pre-donated and stored at 4 degrees C for 4 weeks, and that recovered from surgical drains, from patients subjected to programmed orthopaedic or heart surgery; 2) to assess the metabolic and functional state of red cells attained from that blood, and 3) to compare the results achieved. MATERIAL AND METHODS: The following data were examined: red cell count, haematocrit, haemoglobin, red cell indicates, white cell count, platelet count, free plasma haemoglobin, red cell morphology, glucose, cholesterol, triglycerides, phospholipids, serum proteins and their fractions, ions, histamine, red cell glucose and amino acid transport, and ATP and 2,3-DPG content. RESULTS: The red cells, haemoglobin and haematocrit concentrations in POA blood did not show significant variations during the storage for 4 weeks and their values were significantly higher than found in drained blood. The biochemical values showed heterogeneous variations. Glucose and amino acid uptake by red cells of POA blood slightly decreased in the first 2 weeks of storage but always less than measured in SDR red cells. In POA blood it was noticed a progressive decrease in intra-erythrocytic ATP and 2,3 DPG, those levels being normal in SDR. DISCUSSION: In spite of lower haematocrit and haemoglobin but higher free plasma haemoglobin content, drained blood had higher ATP and 2,3-DPG concentration than pre-deposit, stored blood. Drained blood showed also less ion alterations and probably a lesser immunosuppressor capability. Thus, postoperative blood recovery seems a good source of red cell, with high oxygen transport power, and so, alone or in combination with pre-donated blood, it may contribute to reduce the necessities for homologous blood and decrease its risks.

IgE binding proteins in honey: discussion on their origin.

Pollen proteins, most frequently from Compositae plants, and glandular enzymes from Hymenoptera insects are the only honey allergens involved in every case of honey sensitization reported so far. Surprisingly, we found three patients, all showing the same pattern of honey sensitization with clinical history, cutaneous test and specific IgE clearly positive to honey crude extract but not to the aforementioned components. IgE binding bands, mainly at 54, 46, 17 and 16 kDa, were recognized by the sera of the three patients on blots following electrophoretic separation of a local honey extract under dissociating conditions. Attempts to identify these proteins with the most common honey allergens by means of SDS-PAGE immunoblotting failed, leaving open the question on the origin of protein allergens in cases of honey allergy. Thus, if bee-derived components are not proven to be involved in honey sensitization, other protein sources, such as nectar, should not be disregarded.

Variations in the concentrations of airborne Olea pollen and associated pollinosis in Córdoba (Spain): a study of the 10-year period 1982-1991.

The amount and the seasonal and daily changes in the concentrations of Olea pollen grains in the atmosphere of Córdoba (Spain) have been studied over a 10-year period. The year by year seasonal variation pattern and the theoretical intradiurnal variation model are presented. The data show a high annual variability, median concentrations varying from 75 g/m3/h in 1983 to 1413 g/m3/h in 1986. A steady increase in the total amount of pollen is attributed to the climatological characteristics of the period studied. On the other hand, the clinical data show that the number of cases of Olea allergy has increased considerably during this period, probably more because of changes in the quality of the atmosphere than because of the increase in the amount of antigen present in the air.