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C Pereira,
G Loureiro,
A Martinho,
A Paiva, B Tavares,
D Machado,
R Nunes,
S Pedreira,
A Henriques,
M L Pais,
A Segorbe-Luís
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ABSTRACT: T cell receptor excision circles (TREC) on CD31+ T cells are related to recent thymic emigrant cells (RTEs). The involvement of the functional thymic tissue occurs early in the IgE-mediated allergic reaction, and in response to specific immunotherapy (SIT).
Evaluation of specific immunotherapy effects on TREC number in peripheral T cells in patients allergic to Dermatophagoides pteronyssinus (Dpt).
85 respiratory allergic patients (both genders), 41 of them (Group II) under maintenance treatment to Dpt SIT (21 sublingual-SLIT, and 20 subcutaneous-SCIT), were selected. The allergic patients (Group I) without specific treatment were submitted to an allergen challenge test (22 nasal and 22 conjunctival). Peripheral cell analysis was performed immediately before treatment and 60 or 240 minutes after allergenic extract administration. TREC quantification was performed in CD4+CD31+ and CD8+CD31+. The results were expressed per 100.000 cells related to RTEs. Samples from 10 healthy individuals (Control - Group III) were obtained with the same method.
The value of TRECs on RTEs was constant in control groups. For Group I patients (nasal or conjunctival test), TREC quantification in CD31+ T cells showed relevant individual changes, even in the patients tested earlier (60 minutes), and statistical significant at 240 minutes. Both SCIT and SLIT had also demonstrated enormous individual changes, particularly on TRECs/CD4+CD31+ cells assay. Basal values in Group III were significantly higher than those observed in active patients groups.
Thymic functional activity is earlier involved in the allergic reaction and SIT IgE-mediated allergy is able to induce RTEs in the periphery, particularly TRECs/CD4+CD31+ cells. Both SLIT and SCIT showed reduced RETs in the periphery, probably due to maturation of regulatory T cells. Our results suggest a crucial role of the functional thymic tissue on the central mechanism of this therapy.
European annals of allergy and clinical immunology 04/2012; 44(2):61-72.
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ABSTRACT: Inhaled combined therapy improves the pulmonary function in asthmatic patients. The effect on the airway hyperresponsiveness (AHR) and the efficacy of different pharmacological schedules is not well clarified on adolescent asthmatics.
Evaluate the responses to different combined inhaled therapies in adolescent asthmatics and study its impact on exercise induced AHR.
Basal lung function tests (LFT) were performed in 30 adolescents (13 to 16 years old; 19 female) with allergic asthma. They were submitted to exercise challenge test (EC) followed by bronchodilator test (BD). During 4 weeks, 15 adolescents were submitted to inhaled fluticasone/salmeterol (group A) and other 15 to inhaled budesonide/formoterol (group B). After this period, they underwent another functional evaluation as previous.
Before treatment, pulmonary function was similar in both groups. After 4 weeks of treatment, these groups showed an improvement of the basal LFT (p = 0.001 for FEV1 in both), decrease on bronchoconstriction induced by exercise (NS for both) and less recovery on BD response (p = 0.001 and 0.002, for FEV1 respectively groups A and B). Group B showed a better performance, with higher improvement of basal FEF 25/75 (p = 0.001), reduced bronchoconstriction response to EC (p = 0.008 for FEV1) and fewer response to BD test (p < 0.0001 for FEV1 and 0.024 for FEF 25/75) No adverse events were observed.
After 4 weeks of inhaled combined therapy, these patients improved their pulmonary function and bronchomotricity. Those under budesonide/formoterol showed the highest improvement. These medications are a safe measure in controlling the asthma in these patients.
European annals of allergy and clinical immunology 02/2012; 44(1):12-7.
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ABSTRACT: BACKGROUND: The primary role of infections in chronic urticaria (CU) is controversial. We hypothesised that streptococcal tonsillitis (ST) could be a primary cause of CU or acute recurrent urticaria (ARU). METHODS: Retrospective study of 14 outpatients observed between January 2000 and December 2009, with CU/ARU and clinical and/or laboratorial suspicion of an aetiopathogenic link with ST. Clinical history, objective examination and laboratorial study were looked for. Three groups were defined: spontaneous resolution of urticaria, resolution after tonsillectomy, and still symptomatic. RESULTS: In these patients, a causal relationship between ST and urticaria is supported by: markers of streptococcal infection, the perception of a clinical relationship between tonsillitis and urticaria, the decrease of urticaria severity with early antibiotherapy to tonsillitis and urticaria resolution after tonsillectomy. CONCLUSIONS: Our study encourages the investigation of tonsillitis in these otherwise idiopathic patients, especially until young adulthood and even in the absence of any symptoms.
Allergologia et Immunopathologia 10/2011; · 1.04 Impact Factor
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Allergologia et Immunopathologia 01/2011; 39(4):242-3. · 1.04 Impact Factor
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Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2011; 21(2):154. · 2.27 Impact Factor
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ABSTRACT: High-resolution computed tomography (HRCT) is a widespread medical imaging method for the study of thoracic diseases. In asthma it is very useful particularly when it is difficult to achieve an effective control of disease, and in severe deterioration.
It was intended to evaluate the imaging changes by HRCT in asthmatic patients and to assess the expression according to the symptoms and duration of disease.
Thirty three patients from the Outpatient Department, with asthma classified in the different clinical severity stages according to GINA, were randomly included. They were submitted to HRCT (Somaton Plus-4, Siemens). The lesions were classified in reversible (mucoid impaction, acinar pattern centrilobular nodules and lobar collapse) and irreversible (bronchiectasis, bronchial wall-thickening, sequellar line shadows and emphysema).
The 33 asthmatic patients (20 female) had an average age of 44.76 +/- 16.98 years and a mean disease evolution time of 23.39 +/-14.83 years. 30% had mild persistent asthma, 43% moderate persistent asthma and 27% severe persistent asthma. All the patients were under inhaled corticotherapy. Only 6 patients had normal HRCT 4 with mild persistent asthma (4 to 25 years of duration of disease) and 2 with moderate persistent (10 to 48 years of duration of disease). 81.81% of the patients had changes in HRCT, being the irreversible lesions the most frequent. The most important irreversible lesions were observed in severe asthma patients with longer duration of disease. All the patients with reversible lesions had also irreversible changes. Most of the bronchiectasis were centrally located and were found in severe asthma patients. Irreversible changes were identified in 3 patients with mild asthma and a maximum of 6 years of duration of disease.
HRCT findings were related with asthma severity and long lasting disease but there are some asthmatics that also present early abnormalities, even in milder forms. All the groups of asthmatic patients presented all types of imaging changes, including the irreversible ones. In asthma these changes can be the result of individual patterns of response to frequent exacerbations, leading to a persistent chronic inflammatory process that will determine airway remodelling, even in early stages of disease and/or mild asthma.
European annals of allergy and clinical immunology 10/2009; 41(5):139-45.
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Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2009; 19(3):242-4. · 2.27 Impact Factor
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ABSTRACT: Overweight and obesity are major health issues in Western societies. They are related with a higher risk of different co-morbidities but their relationship with airway hyperresponsiveness (AHR) is still under discussion. Nevertheless, they are related to higher severity in asthma and other respiratory diseases. The aim of the study was to analyze the AHR in individuals with normal lung function without respiratory disorders, according to body mass index (BMI) calculation.
We performed clinical observation and basal lung function tests (LFT) in 595 consecutive individuals in order to exclude respiratory disease. 377 individuals fulfilled the criteria of normal values according international guidelines. They were submitted to standardized treadmill exercise test followed by bronchodilator test. FVC, FEV1, FEF 25/75, RV and Raw were obtained at different conditions according to BMI groups (I: lean; II: normal; III: overweight; IV obese).
55.2% of the sample was overweight or obese, and a signficant relationship was found with female gender and older ages (p=0.0046 and p<0.0001 respectively). The positive response to exercise test or bronchodilator beta2 agonists was not significantly frequent compared with the other groups. In obese individuals the exercise markedly reduced basal Raw and increased FEF 25/75. Lean individuals showed higher basal values of RV that was reduced upon exercise. Response to 12 agonists showed no differences according to weight biotypes.
BMI hampers lung function in normal individuals, and seems not to be related to AHR. Regular exercise should be encouraged in overweight and obese individuals, since it increases their bronchial permeability as shown in lower frequency of positive exercise tests. The same is advisable for lean individuals for different reasons. Their increased basal RV and Raw improve upon exercise. Despite overweight and obesity are being related to a low-grade of basal systemic inflammation, there was no association with a higher basal bronchial hyperresponsiveness in these individuals.
European annals of allergy and clinical immunology 01/2009; 40(4):130-7.
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ABSTRACT: An autoimmune pathogenic mechanism is implicated in about one-third of patients with chronic urticaria (CU), involving circulating functional autoantibodies to either the high affinity IgE receptor (LgG1/IgG3 anti-FcARI) or to IgE, with histamine releasing activity. New therapeutic approaches had been developed for patients with severe or unresponsive to treatment symptoms, including the use of intravenous immunoglobulins (IVIG) as immunomodulators.
To assess the efficacy of IVIG treatment in patients with evidence of autoimmune CU.
A group of 29 patients (F = 20, M = 9) with the diagnosis of autoimmune CU were selected from the outpatient department. All the patients showed daily symptoms of urticaria and/or angioedema, with unsatisfactory response to conventional therapy and a positive intradermal autologous serum test (AST). They were submitted to low dose of IVIG treatment each 4 weeks (0.15 g/kg), for a minimum of 6 months and a maximum of 51 months. They were evaluated for clinical scores, need of oral medication and AST results, before and after treatment.
A clinical improvement was observed in 26 patients, with reduction of urticaria or angioedema complaints (p < 0.0001) and decreasing need for oral antihistamine medication (p = 0.002). 3 patients drop-out the treatment: one depending of severe adverse event and the other 2 with no response after the 5th treatment. 19:26 patients achieved complete remission of symptoms. A reduction of histamine-releasing activity was found in the majority of the patients, documented by the decrea, se of reactivity in AST at the end of the treatment (p = 0.002). 20 patients remained without symptoms during 12 months after. the active treatment, and the other 6 only reported non-severe complaints.
IVIG is an effective therapeutic option in patients suffering from severe CU refractory to conventional treatment, in which autoimmune mechanism is involved. The efficacy persists for at least 12 months after treatment. However, the number of infusions needed to achieve clinical control, showed great range between patients.
European annals of allergy and clinical immunology 10/2007; 39(7):237-42.
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Allergy 05/2007; 62(4):452-3. · 6.27 Impact Factor
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ABSTRACT: Despite the benefits of specific immunotherapy (SIT) being clinically well documented for allergic diseases, new IgE specificities to SIT extract allergens could be induced during the treatment. The authors evaluated these changes in patients allergic to Hymenoptera.
Six patients allergic to Hymenoptera venom were included in the study. Specific IgE (sIgE) levels determination and IgE immunoblots to Apis mellifera, Vespula spp. and Polistes spp. venom were performed before and after one year of SIT.
All patients had sIgE levels reduction, after the first year of treatment, except one in whom there was an increase in sIgE levels to Apis mellifera venom, and two patients that maintained a similar value for Vespula spp. venom sIgE before and after one year of treatment. The immunoblot analysis revealed that most of the bands detected before beginning SIT, decreased in intensity or disappeared after one year of treatment. 3/6 patients developed new IgE specificities to venom extracts: one patient to the venom allergens in the treatment, other patient to allergens in other venom and another patient to both. After one year of treatment one of these patients tolerated a field sting by the corresponding insect. The newly recognised proteins were all minor allergens.
These results confirm that sIgE levels tend to reduce during SIT, and the bands identifying some allergens in the blot tend to decrease or disappear. Nonetheless venom SIT can be responsible for the induction of new sensitisations to other venom allergens, apparently without clinical relevance.
European annals of allergy and clinical immunology 06/2005; 37(5):171-6.
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ABSTRACT: Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy.
We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy.
The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic focalisations were present for all the patients, whereas bowel focalisations were only observed for the subcutaneous route of administration. Sublingual SIT did not induce axillary or intestinal inflammatory focalisations, even though the patients had swallowed the allergenic extract. The uptake coefficient in individualized areas corrected to the uptake coefficient background was also studied.
For the subcutaneous route of administration, except for glutaraldehyde-modified allergen, the local inflammatory activity at the allergenic injection site was significantly higher in depth and was time dependent, maintaining activity even after complete disappearance of the erythema and/or wheal. These results express a prompt inflammatory involvement of the immune system with this allergenic therapy, which was unexpected until now. We also observed differences concerning allergic diseases, the type of allergenic extracts and routes of administration.
European annals of allergy and clinical immunology 01/2005; 36(10):375-86.
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C Pereira,
E Pedro, B Tavares,
M B Ferreira,
I Carrapatoso,
P Rico,
G Loureiro,
F Rodrigues,
M C Santos,
A G Palma-Carlos,
C Chieira
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ABSTRACT: We studied 4 patients (3 adult females + 13y old boy) with latex allergy. All patients had anaphylaxis related with latex and oral-latex-fruit syndrome. All 3 females had severe symptoms in the workplace. The boy had spina bifida with 9 previous surgeries and needed further surgical interventions. Positive skin prick tests (SPT), the presence of serum latex specific IgE (CAP-RAST, Pharmacia-Upjohn, Sweden- class 3 in the 3 females and class 4 in the boy) demonstrated the sensitisation. All 4 patients were treated with specific immunotherapy (SIT) with aqueous extract (ALK-ALK-ABELLO SA, Spain) administered subcutaneously at the hospital, by a modified rush schedule. A maintenance dose (MD) of 0.35_g protein was established according to the magnitude of local reactions (LRs). In one patient a higher dose induced the appearance of a systemic reaction (SR) 40 min after administration, which promptly remitted with treatment. After reaching MD, all 3 females remained assymptomatic at workplace. A challenge test with latex gloves was performed. Two months after MD was reached 2 females had no symptoms and one other had mild symptoms of rhinoconjunctivitis. The boy was subjected to a surgical intervention with no allergic reaction. We also observed a reduction on skin reactivity to latex in all patients by prick tests. We consider SIT with latex to be highly effective, safe and well tolerated provided we use this dose of the allergenic extract.
European annals of allergy and clinical immunology 07/2003; 35(6):217-25.
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ABSTRACT: Goat's milk (GM) allergy not associated with allergy to cow's milk (CM) is a rare disorder. Caseins have been implicated has the major allergens eliciting symptoms.
We report the case of a 27 years-old female patient that experienced two episodes of urticaria related to ingestion of goat's cheese (GC). She tolerated CM, dairy products and sheep cheese. Skin prick tests were performed with GM, CM, bovine casein and alpha -lactalbumin and fresh milk and GC. Serum specific IgE to GM, CM and its fractions, and GM and CM immunobloting assays with inhibition were also evaluated.
Skin tests were positive to GM and GC and negative to CM. GM immunoblot showed an IgE-binding 14 kDa band that was totally inhibited after serum pre-incubation with GM.
Allergens other than casein can be involved in allergy to GM. Even small quantities of protein can elicit symptoms.
Allergologia et Immunopathologia 35(3):113-6. · 1.04 Impact Factor
