Modulation of beta 2-adrenoceptors in human lymphocytes by in vitro stimulation with mediators.

Since Szentivanyi established the beta-adrenergic theory, many attempts have been made to explain the dynamics of bronchial hyperreactivity and cytotropic allergic reaction by this mechanism. In previous work, we found that beta-adrenoceptor numbers were decreased in symptomatic patients and after specific antigenic exposure. As a result, we postulated that this might be due to mediator activity. Blood was extracted from 46 healthy donors for this study. Radioligand [125I]-iodocyanopindolol was used for beta-adrenoceptor determination in peripheral blood lymphocytes following Brodde's method. Student's t test was used for statistical analysis. beta-Adrenoceptor number was determined before and after exposure to mediators (histamine, PAF, LTD4), and after melittin (phospholipase A2, PLA2, activator) exposure. A significant decrease was obtained after histamine (p < 0.05), LTD4 (p < 0.05) and melittin (p < 0.001) exposure; PAF did not modify the number of beta-adrenoceptors. In conclusion, our results confirm that down-regulation of beta-adrenoceptors can be induced by mediator release.

Modulation of beta 2-adrenoceptors in lymphocytes of allergic patients after in vitro antigenic stimulation.

In this study, we assessed the effect of antigen-specific stimulation on beta-adrenoceptors of human lymphocytes in order to study the beta-receptor atopy theory of Szentivanyi. Determination of these receptors was basically carried out as described by Brodde et al., utilizing [125I]-cyanopindolol as ligand in control and allergic patients before and after stimulation with specific antigen. We found that in vitro the specific antigen-antibody reaction induces a decrease in beta-adrenoceptors. This alteration takes place in patients with rhinitis and asthma with sensitization to Dermatophagoides and grass pollen, regardless of their baseline clinical status. Therefore, in view of the results, we question the validity of Szentivanyi's atopy theory. We hypothesize that the modification in the beta-adrenoceptor system is a consequence rather than the cause of the activity of atopic diseases.

Number of beta-receptors in rhinitic pollinic patients.

The study was carried out on venous blood from 67 patients with seasonal rhinoconjunctivitis caused by sensitization to grass pollen and 30 control individuals. Total IgE determination, antigen-specific histamine release test against two concentrations of Phleum pratense, and quantification of beta 2-adrenergic receptor numbers in lymphocyte membrane of peripheral blood were done on all patients. Those pollinic patients who were asymptomatic at the time of the study had 500.07 +/- 237.27 receptors/cell; no significant differences were established with the control group, with 541.53 +/- 123.63 receptors/cell. However, both the control group and asymptomatic patients had receptor numbers which were significantly higher than those of symptomatic pollinic patients, with 376.81 +/- 158.65 receptors/cell (p < 0.01 and p < 0.05, respectively). The average decrease in number of receptors in symptomatic pollinic patients was 30.42% in relation to controls and 24.65% in relation to asymptomatic patients. Within the subgroup of pollinic patients, studied both in and out of season, the number of beta 2-adrenergic receptors had an average decrease of 13.22% during pollination, with 363.7 receptors/cell. Once the pollination season was over, this figure increased to 419.1 receptors/cell, establishing significant differences with p < 0.025. The number of beta 2-adrenergic receptors did not correlate with total seric IgE figures or with antigen-specific histamine release. These data indicate that the decrease of these receptors does not constitute the causal factor of atopic diseases; it seems more likely to be a consequence of the same.

Number of beta-receptors in patients allergic to Dermatophagoides pteronyssinus.

This study was carried out on 96 atopic patients with monosensitization against Dermatophagoides pteronyssinus and 30 control individuals. The patients were divided into 3 subgroups: 27 asymptomatic patients, 27 patients who only presented nasal symptomatology, and 27 patients with marked bronchial symptomatology. Total serum IgE, antigen-specific histamine release, and the number of beta 2-adrenergic receptors in peripheral blood lymphocytes in all patients were determined. The control group presented the highest number of beta-receptors in comparison with the bronchial symptomatic and nasal symptomatic patients. However, asymptomatic patients presented numbers of beta-receptors similar to controls, with no significant differences between both groups. No significant correlation was found between beta-adrenergic receptors and levels of total serum IgE. On the other hand, correlation between beta-receptors and specific histamine release was detected only in symptomatic nasal patients. It can be postulated that the decrease in beta-receptors is a consequence, and not the cause, of atopy.

Decrease of beta-receptors after the antigen-specific bronchial provocation test in bronchial asthma.

Airway hyperreactivity to different stimuli is a characteristic feature of bronchial asthma. The beta-adrenergic theory, as proposed by Szentivanyi in 1968, tried to explain with beta-adrenergic dysfunction, the cause not only of bronchial hyperreactivity but of all atopic diseases. In a previous work, we found that asymptomatic asthmatic patients presented a number of beta-receptors similar to that of a normal control group, while symptomatic asthmatic patients presented a significantly decreased number when compared to both groups (40% decrease). In view of these results, we proposed to study the possible changes in the number of beta-receptors in asymptomatic asthmatic patients after a bronchial provocation test. Fifteen patients, diagnosed of bronchial asthma and sensitive to the house dust mite, D. pteronyssinus, were studied. All were free of medication and asymptomatic at least 90 days before the study. A test of specific bronchial provocation was performed on 10 patients, determining the number of beta-receptors in basal conditions, after 30 minutes and 24 hours. The other five patients underwent an unspecific provocation test with methacholine, with determination of the beta-receptor number at basal conditions, and 24 hours later. Only a significant decrease (30.4%) was found in the beta-receptor numbers, 24 hours after specific bronchial provocation with p less than 0.025 with the Student test for paired data. With regards the beta-adrenergic theory of atopy, in our opinion our results show that the detected decrease of beta-receptors would be the consequence and not the cause of atopic diseases.

Variations of histamine release in an atopic population. II. Clinical situation according to age and duration of immunotherapy.

Mediators released as a consequence of allergen-IgE interaction constitute the elements responsible for the clinical manifestations of allergic diseases. To date, numerous mediators have been described although histamine is the fundamental agent in the majority of these reactions. In the present work, we analyzed the influence of 3 different factors (sex, age and duration of immunotherapy) on "in vitro" antigen-specific histamine release. The study was done on 226 individuals mono-sensitized to Dermatophagoides. Of these patients, 195 were asthmatics and 31 rhinitics; their ages ranged between 1 and 72 years, with an average of 21.87 +/- 15.36. There were no significant differences in histamine release capacity in relation to the patient's sex. As to age, there were marked differences in patients older than 40 years; these patients released less histamine (in percentage as well as in total levels) than those patients with less than 20 years of age, with a probability of less than 0.05. When comparing the different groups studied in relation to the time of immunotherapy, we found a statistically significant decrease in histamine release percentages between those patients with less than 1 year of immunotherapy and those with more than 3 years (p less than 0.05), reaching a reduction of 16.33%.

Food allergy to Helix terrestre (snail).

Among the rare foods capable of producing food allergies is the snail (Helix terrestre). The snail is a delicacy eaten in Spain, France and Portugal. This study presents the findings of an allergic study of 10 patients with this infrequent food allergy during the past 10 years. The shock organ in the majority (80%) of these patients was the bronchial tree. Six of them did not have any digestive or skin symptoms which are usually seen in cases of food allergy. All patients manifested the symptomatology after ingestion of Helix terrestre. Two also had reactions after eating Patella vulgata (limpet). The snail and the limpet are within the phylogenetic line of molluscs, i.e. of gastropods. All patients tolerated the ingestion of cephalopods and bivalves which belong to two other phylogenetic lines. Skin tests to seafoods (squids, prawns, lobsters and clams) were negative for all patients. This suggests that the sensitizing antigen is probably a protein found only in gastropod molluscs. Skin tests along with the histamine release test were valid diagnostic methods for this food allergy. The limited bibliography on this subject is probably due to the fact that the consumption of snails as well as limpets is limited to specific geographical areas.

The value of total IgE determination in mite allergy.

Our aim was to study the behaviour of patients with perennial respiratory allergy in relation to total IgE production. We chose patients allergic to house dust mite Dermatophagoides pteronyssinus, because this is the most representative perennial antigen. The total IgE in a wide group of patients was evaluated in relation to diagnosis, clinical activity, and seasonal changes. We also studied the possible changes in relation to immunotherapy. The total IgE was measured through enzyme immunoassay (Kallestad). To compare the results, a Student's test for independent data was performed and a statistically significant difference (p less than 0.001) in the IgE levels was found between the rhinitis and asthma groups with or without associated rhinitis. We did not obtain any differences between the groups in relation to clinical activity or seasonal changes. In relation to the possible changes in IgE levels according to the duration of immunotherapy, we observed a mild elevation before 7 months and between 13 and 24 months of treatment, without any significant differences with respect to basal levels. The determination of total IgE seems to us a valid and necessary test to complete the diagnosis of the existence of a cytotropic hypersensitivity mechanism in respiratory pathology. However, it seems to be less sensitive because it does not detect changes with respect to clinical activity, seasonal changes or duration of immunotherapy when dealing with perennial antigens.

Basophil degranulation test in house dust mite allergy: diagnostic value.

After reviewing the experience of various authors we applied the Basophil Degranulation Test (BDT) in the study of sensitization to Dermatophagoides pteronyssinus, so as to evaluate its diagnostic use. Fifty-five patients with asthma and/or rhinitis and a positive skin test to the mentioned antigen, as well as 20 control subjects were studied. The results demonstrated a sensitivity of 65.5% and a specificity of 80% with an efficiency index of 69.5%. We did not find any significant correlation with the histamine release test (r = 0.236). The data obtained and the proper limitations of the technique led us to consider the BDT to have a limited application in routine allergy diagnosis.

A rare case of food allergy: monosensitivity to kiwi (Actinidia chinensis).

We present a case of hypersensitivity to kiwi in a 26 year-old patient with no previous atopic history. The first reaction episode occurred a few minutes after kiwi ingestion, presenting with a localized pruritic reaction. This symptomatology repeated itself a few months later, again immediately after eating kiwi and was accompanied by dysphagia, vomiting and urticaria. In the complementary laboratory analyses a total IgE of 187 IU/ml was appreciated. The skin test to inhalant and food antigens were negative, while the kiwi extract produced a + + + + reaction. The histamine release test was positive (20%). Specific IgE levels (Kallestad) demonstrated results of 0.35 AEU/ml (class I). Specific IgG4 levels were normal and the hemagglutination test was negative. With the above results, we concluded that we were dealing with a case of monosensitivity to kiwi which was probably IgE mediated.

Variations in antigen-specific histamine release related with immunotherapeutic treatment.

The present study analyzes the variations in the percentage of histamine release of 34 allergic patients receiving immunotherapy; the determinations were realized at two different periods of their immunotherapeutic treatment, that is, at an average of 18 months (mite allergy group) and 12 months (grass allergy group) after the first determination. We found that the percentage of histamine release decreased significantly in the second determination in relation to the first, and that this decrease was more intense when more time elapsed between both determinations.

Variations of histamine release in an atopic population. I. Clinical situation and seasons.

Two hundred and twenty-six patients (195 asthmatics and 31 rhinitics) sensitive to D. pteronyssinus were studied. Histamine release tests were performed on them and the results obtained were analyzed with respect to 3 variables: clinical situation (symptomatic and asymptomatic), diagnosis (asthma or rhinitis), and the month of extraction. There were no significant differences between the total and basal histamine in the various groups. The symptomatic individuals (48.66 +/- 29.66 ng/ml) released a greater amount of histamine than the asympomatic group (39.47 +/- 21.07 ng/ml) (p less than 0.05). There was no difference with regards to the diagnosis, although symptomatic asthmatics released more histamine than active rhinitics (p less than 0.01). These patients released more histamine during spring and autumn than during the other two seasons.

Late asthmatic reaction in a hairdresser, due to the inhalation of ammonium persulphate salts.

Persulphate salts are among the various chemical substances that can cause occupational diseases in hairdressers. We present the case of a 21 year-old female who worked in a hairdressing salon for five and a half years. Five years prior to consultation, she presented with rhinitic symptoms and wheezing dyspnea which were related with her working environment. The routine laboratory examinations carried out on the patient were found to be normal. Among the various allergic exams performed there was an elevated total IgE. The provocation test with histamine was positive at the concentration of 10 mg/ml, demonstrating mild bronchial hyperreactivity. The test of bronchial exposure to ammonium persulphate was positive with bronchospasm 3-4 hours after this test. With a prior inhalation of betamethasone we were able to block this reaction, but with disodium cromoglycate we were able to block it only partially. We conclude that the patient presented with late onset bronchial asthma due to sensitivity to ammonium persulphate. It has to be pointed out that this patient was a rare case as generally persulphate salts choose to invade and affect the skin. The rarity of this pathology is reflected by the scarce bibliography on this subject.

The protective effect of ketotifen in exercise-induced bronchospasm.

The present study evaluates the protective action of ketotifen on exercise-induced bronchospasm in patients diagnosed with bronchial asthma of different aetiologies. The patients were classified in 2 groups. The first group with seasonal asthma was made up of patients with pollen hypersensitivity, while the second group with perennial asthma was made up of patients with bacterial aetiology or sensitivity to the Dermatophagoides mite. Spirometry and airway resistance measurements (in basal conditions, 5 to 10 minutes after a resistance test which consisted of 6 minutes' free running on a treadmill) was performed on each patient. Those patients in which significant spirometry or Raw alterations were detected received a 15-day treatment of ketotifen (a dose of 1 mg every 12 hours); after this time, the tests mentioned before were repeated. We found that in the seasonal asthma group, ketotifen was effective in protecting against exercise. However, we did not observe the same effect in the perennial asthma group. In the light of these results, we propose the possible existence of different mechanisms in triggering off exercise-induced bronchospasm, according to their aetiologies.