Development and validation of a new Spanish instrument to measure health-related quality of life in patients with allergic rhinitis: the ESPRINT questionnaire.

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.

Bacterial immunotherapy in bronchial asthma.

Nowadays, bacterial etiology is probably the least considered and most controversial in the etiopathogenesis of bronchial asthma. It was in the first decades of this century when several authors insisted on the close relation between infection and asthmatic response. This is why, since antibiotics have appeared, many renowned authors insist on the basic treatment of the infection with antibiotics. Also, the need of immunotherapy with bacterial antigens is being emphasized, considering the importance of this factor in bronchial asthma. Nevertheless, there are some detractors who, in our opinion, do not base their criteria on experience or precise data which support the rejection of the bacterial infectious factor as a causal triggering factor. It has been in the last decade when several authors, Norn among them, confirm the importance of the bacterial antigen, and especially its potentiating role on the inhalant allergens. On the other hand, in the last decade the symptomatic treatment of asthma by means of bronchodilators and corticosteroids is being fomented. That is, the maintenance of the asthmatic patient is being fomented instead of his consequent treatment, fighting the infection. According to our long experience and the positive number of cases obtained, again we insist on the need to treat bronchial asthma with bacterial immunotherapy. Therefore, it is necessary to study this aspect more in depth in order to reach a real knowledge of all of the above.

Bacterial infection as an important triggering factor in bronchial asthma.

It is very surprising that in recent decades, the bacterial infection factor has been so overlooked in the causal treatment of bronchial asthma. Emphasis is put in the viral infection, but the bacterial infection usually associated with it is ignored. In several publications, we have insisted on the importance of the bacterial infection factor in the etiopathogenesis of bronchial asthma. It is alarming that even in the international consensus on its treatment this aspect is overlooked. In the first decades of this century, great importance had already been put on bacterial infection in the triggering of bronchospasm. In this review, we insist on this role of bacterial infection, which comes as a result of our extensive experience in this area, and the fact that in the last 10 years many authors have proven its responsibility at a bronchial mucosa level. In due time, we may be able to prove that the bacterial antigens can potentiate the action of inhalant allergens. Some authors have even proven that the action of these bacterial antigens even more energetically increases the number of intraepithelial dendritic cells in the bronchial mucosa after inhalation of bacterial lipopolysaccharide. Bystander respiratory bacterial infections can also directly modulate T helper 1 and 2 selection parallel to the immune response to inhalant allergens. Recent studies have also proven that in respiratory infection, bacterial antigens hold the main responsibility in the inflammatory and bronchospastic response in the etiopathogenesis of bronchial asthma. Therefore, a consequent treatment of the infection is required, by means of wide spectrum antibiotics, as well as prescription of bacterial immunotherapy, as we have emphasized on other occasions. In conclusion, we must try to cure asthmatic patients and not to maintain them with inhalers and unnecessary corticosteroid therapy, since increasing reactions to corticosteroids are witnessed every day.

Perforation of the nasal wall and hyper-IgE syndrome.

Hyper-IgE syndrome is basically characterized by recurrent infections, chronic eczematous lesions, specific IgE antibodies against Staphylococcus aureus and markedly high serum IgE values. We present the case of an 11-year-boy with no relevant personal or family history, who came to our Department with highly pruriginous papulovesicular skin lesions of 3 years' duration. He presented marked obesity (+4 SD) and micropapulovesicular lesions in the trunk and extension areas of the limbs. The rest of the physical exploration was normal. Complementary studies revealed peripheral eosinophilia, increase in globular sedimentation rate and IgE values of 20,000 IU/ml, a nonspecific reaction to skin tests, and a skin biopsy compatible with atopic dermatitis. Three months later, he presented eczematous lesions in the trunk and limbs, perforation of the nasal wall due to staphylococcal abscess (diagnosed by biopsy), bilateral maxillary sinusitis and IgE values of 59,238 IU/ml. The differential diagnoses are discussed, as well as new diagnostic-therapeutic possibilities.

Influence of immunotherapy on histamine release and other immunological parameters of immediate hypersensitivity in pollinosis.

Specific immunotherapy in pollen-allergic patients leads to a significant time-dependent decrease in the seasonal differences in IgE values, that is, the shorter the duration of immunotherapy, the smaller the difference. Immunotherapy leads to a maximum specific histamine release during the first year, with higher values during the pollen season. Later, the amount of histamine released from basophils decreases gradually in relation to the duration of immunotherapy and the clinical recovery, indicating that this would be a useful parameter in the follow-up of the efficacy of this type of treatment. Inversely, total histamine, which may be considered a parameter indicating the histamine stored in basophil granules, decreases significantly, reaching its lowest values at the end of the first year, with eventual recovery to initial values. From these results we may conclude that hyposensitizing treatment should not be interrupted before 3 years, since the immunological variations of the immediate hypersensitivity parameters take place during the first 2 years, and then stabilize. On the other hand, the correlation between the degree of recovery after hyposensitizing treatment and the duration of the treatment leads us to recommend immunotherapy for periods longer than 2 years.

Variations of intracellular histamine basophil levels after treatment with ketotifen.

As reported in previous studies, ketotifen modifies the number of basophils in peripheral blood, most likely inhibiting their degranulation, which correlates with the lack of exercise-induced respiratory manifestations. In this study, we attempted to measure the approximate amount of intracellular histamine in patients with bronchial asthma sensitized to Dermatophagoides pteronyssinus when they were treated with ketotifen, and compare the values with those of an untreated group and a control group, in order to determine if ketotifen stabilizes the cellular membrane, with the subsequent increase of intracellular mediators. We found that untreated patients had 57% less histamine per basophil than the control group, while treated patients had only 17% less than the controls. This shows that ketotifen acts as a membrane stabilizer, thus inhibiting degranulation and increasing the amount of intracellular mediators.

Importance of IgG4 determination in in vitro immunotherapy follow-up of inhalant allergens.

Choosing the right parameters to recommend immunotherapy in allergologic diagnosis is very important. Therefore, other parameters which are independent of the improvement of clinical manifestations and which indicate the evolution of asthma are very useful. Although a decrease in skin reactions was observed in 20% to 25% of patients in previous studies, since the in vitro techniques appeared, their evolution has been observed. Total and antigen-specific IgE evolution, as well as histamine release from basophils, in immunotherapy were followed as we had presented in previous studies. In this work, we studied 151 patients with asthma and rhinosinusitis, 70 of whom were sensitive to Lolium perenne and 81 to Dermatophagoides pteronyssinus. The parameters mentioned above were used, and the patients underwent immunotherapy at three different concentrations depending on the degree of sensitization. The standard concentration was used in the first group; those patients with very high values in radioallergosorbent test (RAST) and histamine release test (HRT) were given the concentration 1:2; and lastly, the largest group of patients, who presented the highest sensitization both in vivo and in vitro, were given the concentration 1:10. As a complement to the mentioned in vitro techniques, the antigen-specific IgG4 determination (blocking antibody) was also evaluated. As we observed in previous studies, skin test, total IgE, antigen-specific IgE and HRTs showed no significant modifications in any of the three groups, in spite of the very positive clinical evolution over the 6 years. Regarding IgG4 follow-up in pollinic patients, a very significant increase was observed, reaching its highest value after 6 years, at standard concentration and with an increase of 49.4%. In conclusion, we think that antigen-specific IgG4 is the only easily available and suitable parameter existing for immunotherapy follow-up.

Sensitization to Alternaria and Cladosporium in asthmatic patients and its in vitro diagnostic confirmation.

In order to determine the prevalence of airborne mould sensitization and the reliability of the in vitro diagnostic techniques in daily practice (antigen-specific IgE and histamine release test), we performed a 3-year study in 2,200 patients diagnosed with rhinosinusitis and/or bronchial asthma. We found mould sensitization in 101 patients, 20% of whom presented monosensitization against airborne moulds, and the rest associated other sensitizations as follows: 53.7% against Dermatophagoides pteronyssinus, 45% against grass pollen and 30% against Olea europea. The most frequently involved moulds in our patients were Alternaria and Cladosporium. Seventy-six percent of the patients presented sensitization against Alternaria, 56% of whom were monosensitized, 26% presented cosensitization to Cladosporium and the remainder were sensitive to more than two moulds. Regarding Cladosporium, the percentage of patients was similar (66%), although only 23% were monosensitized and 46% presented an associated sensitization against Alternaria. We also observed a correlation between skin tests and both in vitro diagnostic techniques, with a relative sensitivity of the specific IgE determination compared to the skin test of 98% against Alternaria and 90.4% against Cladosporium, whereas the relative sensitivity of the histamine release test was 97.4% for Alternaria and 85% for Cladosporium. In conclusion, we think that in order to confirm the etiopathogenesis of the airborne moulds and before an immunotherapy treatment is indicated, the positive skin reactions should be confirmed by means of reliable laboratory diagnostic techniques, such as antigen-specific IgE determination and histamine release test.

Mechanism of ketotifen action in hypersensitivity reactions. Its effect on cellular enzymatic activities.

In this study we observed that asthmatics had less methyltransferase activity and greater phosphodiesterase activity than healthy individuals. These enzymatic activities were nearer to values obtained in healthy individuals when we preincubated cells with ketotifen. The modulator effect of this drug on these two enzymes permits, on the one hand, to re-establish the beta-receptor numbers expressed on the membrane, and on the other hand, to inhibit mediator secretion provoked by antigenic stimulus. With its action on adenylate cyclase and phosphodiesterase activities, it allows cAMP intracellular accumulation and hinders the secretory process. Through its action on methyltransferase activity, it is responsible for the normalization of beta-receptor expression observed in asthmatic patients treated with ketotifen.

In vitro ketotifen protection in bronchial hyperreactivity.

There are drugs, such as ketotifen, that inhibit bronchospasm through different mechanisms. In this study, we looked at the changes in the number of sanguineous cells that ketotifen produces, especially in basophil cells, that could explain its prophylactic effects in bronchial hyperreactivity disclosed by exercise, as well as its relation to the variations in basal and total histamine in blood. 22 patients were selected, with a diagnosis of extrinsic bronchial asthma with sensitization against Dermatophagoides, and were compared to a control group. They all underwent an exercise test. Blood samples were taken before and after exercise in order to measure the number of leukocytes and the changes in basal and total histamine. We found that the number of basophils does not increase after exercise in untreated patients, while it does in the control group and in treated patients. This implies that ketotifen stabilizes the basophil cells, hindering their degranulation and the subsequent liberation of mediators that would produce bronchospasm after exercise.

Influence of seasonal variations on histamine release and other immunological parameters in pollinosis.

One hundred and fifty-six pollen-sensitive patients with sensitization to grass pollen only were chosen for this study; 65 patients were allergic to Dermatophagoides, while 45 were non-allergic subjects with no atopic history. The following tests were carried out on all patients: histamine release of total blood, basal histamine, total histamine, determination of total IgE and specific IgE (RAST) serum levels, serum hemagglutinating antibodies and skin tests. Seasonal increase of IgE was observed, with post-seasonal fall; 50% of the cases reached normal values. However, RAST as a semiquantitative method did not prove to be useful in the detection of variations in specific IgE levels. During pollination, an increase in titers in pollen-sensitive subjects was seen. This was attributed to a humoral immune response epiphenomenon which was independent of IgE. The histamine release test was significantly greater during pollination in pollen-sensitive subjects. The total of stored histamine increased during the months of allergenic exposure.

Correlation between blood eosinophils, T-helper cell activity markers and pulmonary function in patients with allergic and intrinsic asthma.

We studied 21 asthmatic patients (17 with allergic asthma and 4 with intrinsic asthma) who on the date of admittance to our clinic presented eosinophil values higher than 400 eosinophils/mm3 and a marked alteration in pulmonary function. From the day of admittance, eosinophils/mm3 were followed-up for 28-30 days, along with T-helper cell activity markers (IL-2R+) and pulmonary function markers. In patients with allergic asthma with or without topical corticoid treatment, and in patients with intrinsic asthma under treatment with topical corticoids, we observed that the number of eosinophils/mm3 and the number of activity markers (IL-2R+) decreased progressively, with subsequent clinical recovery and improvement in pulmonary function. This was not observed in patients with intrinsic asthma not treated with topical corticoids. We conclude that, as previously demonstrated, the activation and proliferation of eosinophils bear a close relationship with the previous activation of T-helper cells (CD4).

Skin manifestations and immunological parameters in childhood food allergy.

According to Hansen's contact rule, the digestive system should be considered as the main shock organ, yet in food allergy, this is not the case. Very often specific food triggers clinical manifestations not involving the digestive system; that is, reactions are manifested either in the respiratory system, as asthma or rhinitis, or in the skin. In these cases the BALT (broncho-alveolar lymphoid tissue) and GALT (gastrointestinal lymphoid tissue) units play a basic role in the sensitizations. The purpose of this study was to determine the most frequent skin manifestations of food allergy among children, and the most frequently involved foods. We also thought it interesting to evaluate the diagnostic reliability of the different standard immunological parameters utilized by the study team in food allergy. All patients underwent intracutaneous tests with 12 groups of the most frequent food allergens, as well as serum IgE, antigen-specific IgE against foods, and antigen-specific histamine release tests. Antigen-specific IgG4 determination was performed in some cases. The results obtained confirmed previous studies, the most common manifestations being: angioedema (48%), followed by urticaria (31%) and atopic dermatitis (21%). Regarding the frequency of sensitization to different food allergens, in mono- or polisensitization, fish and egg stand out in our environment. Certain food allergens are more frequently responsible for specific skin manifestations. Thus, for fish sensitization, the most frequent skin manifestation is atopic dermatitis (50%); for egg sensitization, angioedema is the most frequent skin manifestation (50%); and for milk, urticaria (50%). Finally, and in agreement with previous works regarding the diagnostic reliability of in vitro techniques, we found that the histamine release test offered the highest percentage of diagnostic reliability. Only for sensitization to milk proteins did antigen-specific IgE demonstrate higher reliability. Once again, we stress that our main problem is the lower reliability of skin tests against food allergens than against inhalant allergens. We emphasize the importance of food as a major factor in the etiopathogenesis of atopic dermatitis, as well as the need to complement the study, when possible, by means of the in vitro techniques described.

Reliability of histamine release test in dust mite allergy: influence of the degree of sensitization.

The histamine release test has been proven to be a very useful method for in vitro diagnosis of IgE-mediated allergy to inhalant and food allergens, as well as for the immunotherapy follow-up of the allergic patient. The aim of the present study was to assess the influence of the degree of sensitization in allergic patients sensitive to Dermatophagoides pteronyssinus on their dose-response curves in histamine release tests. To achieve this aim, we studied 109 D. pteronyssinus allergic patients and 25 healthy control subjects. Intracutaneous skin test, D. pteronyssinus-specific and total IgE quantitations, and histamine release tests were carried out in all the patients. In the case of the histamine release test, five D. pteronyssinus extract concentrations were used (2822.5, 282.25, 28.22, 2.82 and 0.28 UBE/ml), and two patterns of histamine release in sensitive patients were found: one with maximal histamine release at the highest antigen concentration (group I) and the other with maximal release attained at lower concentrations (group II). A sensitization score was designed, after the results from specific IgE and intracutaneous skin tests. There were significant differences (p < 0.05) in antigen-specific and total IgE levels, and in papule diameters and sensitization scores, between the control group and groups I and II. Both groups showed significantly higher (p < 0.05) histamine releases than the control group in response to anti-IgE antibodies. When stimulating the cells with anti-IgE antibodies, histamine release in group II was higher than in group I, although this difference was not significant. Finally, the best correlation between sensitization score and antigen-specific histamine release was found at the 2.82 UBE/ml concentration (r = 0.84, p < 0.001).

Diagnostic reliability considerations of specific IgE determination.

Total IgE determination constitutes a good method for the screening of atopic diseases, though its actual value is controversial because normal values of total IgE do not exclude the existence of atopic disease, and high values of total IgE are not pathognomonic of atopy by themselves. The first step in identifying an atopic individual as such, after doing his anamnesis, can be carried out by means of total IgE determination. Most atopic individuals have high IgE values, but a normal result must be carefully interpreted: age and season-related variations must be considered. In general, atopic patients with IgE values greater than 1000 Ul/ml, always have positive specific IgE against some allergen. Antigen-specific IgE will be the next step in the in vitro identification of the responsible allergen. Nowadays, there are more than 400 characterized allergens available for in vitro diagnostic tests and several useful methodologies for specific IgE determination. Specific IgE results obtained with the different methods vary significantly, with absolute agreement in 55-65% of the cases, differences in one IgE class in 20-30% of the cases and differences in more than two classes in 5-10%. The specificity of the anti-IgE antibody used in the assay is of critical importance because any contaminant antibody can render unspecific results. On the other hand, it must be pointed out that there is a compromise between specificity and sensitivity, such that an increase in the sensitivity of a technique leads to a decrease in its specificity. It cannot be said that there is one method which is better than the others; it is better to examine them individually, allergen by allergen. Thus, specific IgE determination varies depending on the type of allergen. In general terms, for inhalant allergens, specificity and sensitivity of the methods are within the range of 85-95%, but these values (especially the specificity) decrease in the case of food allergens, and they are still lower when the allergen is a beta-lactamic drug. There is a good correlation between clinical history and specific IgE against inhalant allergens, and a lower correlation in the case of food allergens. Due to the fact that most food allergens are not standardized, the definitive diagnosis of food hypersensitivity is achieved by means of provocation tests. Nevertheless, negative specific IgE (7-18% of the cases) does not rule out a sensitization against the tested allergen, and a positive specific IgE without symptoms must be carefully interpreted because it can be due to a low degree of sensitization, unable to express clinical symptoms at this moment, but useful in the future as a guide on the disease course. In the evolutive period of the disease, specific IgE levels can be modified in a natural way (in beta-lactam allergy, 50% of the cases with specific IgE become negative after a year), or as an effect of the treatment (e.g., after immunotherapy in the case of Hymenoptera venom allergy), or it can remain positive for a long time, as in the case of pollinosis. On the other hand, the cutoff of the method, and subsequently the range of values to be considered as positive, will depend on the allergen studied. While inhalant allergens (with the exception of some molds) offer relatively high mean values of specific IgE, food and drug allergens yield less significant values. In general, a class greater than 2 is interpreted as clinically significant, class 1 as dubious or negative (depending on the allergen) and class 0 as negative. In the interpretation of the results, the possible presence of IgG and anti-IgE antibodies, capable of modifying the results, will be taken into account. When comparing the diagnostic reliability of specific IgE with respect to other allergologic diagnostic methods, we find a significant and positive correlation of this technique with skin tests (but never greater than 90-95%) and with the histamine release test.

Antigen-specific sulphidoleukotriene production and histamine release in pollinic patients.

We studied sulphidoleukotriene (sLT) production, by means of CAST-ELISA (Bühlmann) in 92 atopic (54 pollinic and 38 non-pollinic) patients, and in 9 control subjects, after antigenic stimulation of peripheral blood leukocytes with 20 ng/ml and 2 ng/ml of Lolium perenne pollen extract, in the presence of IL-3. Antigen-specific stimulation of leukocytes from pollinic patients studied during the pollen season led to a sLT production significantly higher (p = 0.03 at 2 ng allergen/ml) than in those studied out of the pollen season. Histamine release was also significantly higher in pollen season than out of the season (p = 0.04 at 20 ng allergen/ml and p < 0.001 at 2 ng allergen/ml). There was a significant positive correlation between sLT production and histamine release (r = 0.67 at 2 ng allergen/ml and r = 0.57 at 20 ng/ml, both p < 0.001), and between sLT production and skin test results (r = 0.5 at 2 ng allergen/ml and r = 0.46 at 20 ng allergen/ml, both p < 0.001). We found that sLT production was lower, although not significantly, in patients older than 40 years, and histamine release was significantly (p = 0.02) higher in women than in men at 2 ng allergen/ml. We conclude that sLT production in pollinic patients is higher when antigenic pressure is increased in the environment, and that sLT quantification by CAST-ELISA might be useful for evaluation of this sensitization, with analogous results to the histamine release test.

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.

Effect of immunotherapy on allergen-specific production of sulphidoleukotriene and histamine.

Numerous controlled trials have demonstrated the efficacy of specific immunotherapy, although its mechanism is not completely understood. Few studies have addressed the effects of immunotherapy on the release of mediators. We measured in vitro sulphidoleukotriene (sLT) and histamine release after specific stimulus (Dermatophagoides pteronyssinus or Lollium perenne) in a group of patients under immunotherapy (n = 35) and compared the results with those obtained in a group of allergic patients without immunotherapy (n = 57). SLT quantification was carried out by cellular stimulation allergen test (CAST)-ELISA and we measured the amount of histamine release using a fluorometric method. We found a significant (p < 0.05) reduction of allergen-specific mediator release on the group of patients under immunotherapy treatment. When we studied the group of patients sensitive to D. pteronyssinus we also observed a significant reduction in sLT release after the in vitro stimulus with anti-IgE. In vitro sLT production could be a good marker for follow-up immunotherapy. This study provides more evidence to support the immunological and cellular changes induced by immunotherapy.

Study of IgE-dependent sulphidoleukotriene cellular releasability.

Cellular releasability of mediators, as termed by Lichtenstein and Conroy (1), can be triggered by interaction with allergens, anti-IgE antibodies or other agonists. Genetic factors can also influence the cell releasability. We studied 104 subjects, including 92 atopic patients (62 sensitive to D. pteronyssinus and 54 sensitive to Lolium perenne) and 12 healthy controls. Sulphidoleukotriene (sLT) production was measured after allergen and anti-IgE stimulus with CAST-ELISA, and histamine release using a fluorometric method. We found a significant sLT production after anti-IgE stimulation, higher than in basal conditions with medium alone. The sLT production was also significantly higher in sensitive patients than in healthy controls. We found 14.5% of healthy and atopic subjects to be non-responders to anti-IgE stimulus. We also found a positive and significant correlation between sLT production and histamine release. Moreover, we observed a significant positive correlation between IgE-dependent and antigen-specific sLT release. We also noticed a decrease in sLT production and a decrease in histamine release with aging. Male patients had a sLT production significantly higher than female patients. With respect to clinical diagnosis, the group of patients with rhinitis had the highest mediator production. Finally, pollinic patients studied during the spring had a higher sLT production to anti-IgE than those studied out of this season. We conclude that quantification of sLT production after anti-IgE stimulation is a useful method to study cell releasability of mediators and that such releasability is higher in atopic patients than in healthy donors. We must emphasize the usefulness in allergy diagnosis of relying not only on the use of methods demonstrating the existence of sensitization to an allergen, but also of techniques able to quantify the ability to respond to that allergen. In this way we would be able to evaluate the clinical and immunological evolution of patients and to follow up the efficacy of their treatment.

Abuse of therapy with corticosteroids in the asthmatic patient and the deficient control of suprarenal function. Indication of therapy with ACTH.

The use of corticosteroids, either oral, parenteral or as aerosol, means a great step forward in bronchial asthma treatment. Nevertheless, given the abuse of their administration, we find more and more frequently, cases of corticodependent bronchial asthma, due to a deficient control in the clinical evolution. For this reason, we performed a study with 39 patients diagnosed with corticodependent intrinsic bronchial asthma. Basal cortisol determination was performed in all, and all of them followed posttreatment with ACTH, antibiotics and mucolytics, as well as follow up of respiratory function parameters and clinical evolution. We found a mean increase in cortisol levels of 488% (basal: 2.49 +/- 0.33 micrograms/dl; posttreatment: 14.59 +/- 2.9 micrograms/dl). Regarding the respiratory function tests, FEV1 improved from 59.38 +/- 4.23% to 68.52% +/- 4.28% (15.4% increase); MEF50 went from 28.62 +/- 3.47% to 35.9 +/- 3.81% (25.4% increase) and MEF25-75 improved from 28.89 +/- 3.47% to 37.05 +/- 3.93% (28.2% increase). Clinical symptomatology and medication improved in general, going from an initial punctuation of 8.5 to a posttreatment score of 7.47. In general, 50% of the patients studied improved from the clinical point of view, only 47.2% had a discrete improvement, and only one patient got worse. Side effects with ACTH treatment appeared in 28.2% of the cases, mainly peripheral edemas, especially in the lower extremities. In conclusion, with patients undergoing lengthy corticosteroid therapy, control of their suprarenal function is absolutely necessary. If a glandular insufficiency appears with low levels of plasmatic cortisol, we advise treatment with ACTH in association with antibiotics.