RESUMO
BACKGROUND AND PURPOSE: Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest. METHODS: From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively. RESULTS: There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2-3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2-3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91â =â 86% and 64/78â =â 82%) compared with pharmacological thrombolysis only (15/32 = 47%; Pâ <â 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0-2] in 54/28% patients and moderate (mRS 0-3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (Pâ =â 0.001). In multivariate analysis age [odds ratio (OR)â =â 0.96, 95% confidence interval (CI)â =â 0.93-0.98], NIHSS on admission (ORâ =â 0.9, 95% CIâ =â 0.83-0.98) and functional ICA-T occlusion (ORâ =â 0.35, 95% CIâ =â 0.16-0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (ORâ =â 9.30, 95% CIâ =â 2.03-42.63). CONCLUSIONS: The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.
Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna/efeitos dos fármacos , Trombólise Mecânica , Terapia Trombolítica , Trombose das Artérias Carótidas/patologia , Artéria Carótida Interna/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reperfusão , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) is effective when performed within 6â h of symptom onset in selected stroke patients ('Tâ <â 6H'). Its safety and efficacy is unclear when the patient has had symptoms for more than 6â h ('Tâ >â 6H') or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. METHODS: Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0-2] or mortality 3â months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. RESULTS: Six-hundred and fifty-four patients were treated before (Tâ <â 6H) and 205 after 6â h or an unknown time (128 Tâ >â 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in Tâ <â 6H patients, vertebrobasilar occlusion was more common in Tâ >â 6H and UOS patients, and middle cerebral artery occlusions less common in Tâ >â 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. CONCLUSIONS: Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6â h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.
Assuntos
Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/prevenção & controle , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Idoso , Procedimentos Endovasculares/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversosRESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Adulto , Anti-Inflamatórios não Esteroides/imunologia , Aspirina/imunologia , Asma/induzido quimicamente , Asma/diagnóstico , Criança , Hipersensibilidade a Drogas/classificação , Hipersensibilidade a Drogas/imunologia , Europa (Continente) , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Guias de Prática Clínica como Assunto , Urticária/induzido quimicamente , Urticária/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Retrievable stents combine the high recanalization rate of stents and the capability of removing the thrombus offered by mechanical thrombectomy devices. We hypothesized that retrievable stents shorten time to recanalization in the multimodal approach for endovascular stroke treatment. MATERIALS AND METHODS: Forty consecutive patients with acute ischemic stroke and undergoing endovascular therapy were included. Treatment included thromboaspiration, thrombus disruption, thrombolysis, PTA, and stent placement. In 17 patients, a retrievable stent was used (group A) in addition to multimodal therapy. The remaining 23 patients constituted group B. Baseline characteristics, occlusion sites, urokinase dose, recanalization rate, and time to recanalization were compared between the groups. RESULTS: Median NIHSS scores were higher in group A compared with group B on admission (19 versus 12.5; P = .018) but were not significantly different at day 1 (14 versus 10; P = .6). Intra-arterial thrombolysis was used in significantly fewer patients of group A than group B (53% versus 87%, respectively; P = .017), and median urokinase dose was lower in group A than in group B (250,000 IU versus 700,000 IU; P = .006). Time to recanalization was significantly shorter in group A compared with group B (median time to recanalization 52.5 minutes versus 90 minutes, respectively; P = .001). Recanalization rate was higher in group A than group B (94% versus 78%; P = .17). CONCLUSIONS: Addition of retrievable stents to the multimodal endovascular approach for acute ischemic stroke treatment significantly reduces time to recanalization and further increases the recanalization rate.
Assuntos
Isquemia Encefálica/terapia , Revascularização Cerebral/instrumentação , Revascularização Cerebral/métodos , Stents , Acidente Vascular Cerebral/terapia , Doença Aguda , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/mortalidade , Angiografia Cerebral , Revascularização Cerebral/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Trombectomia/instrumentação , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Patients who are clinically hypersensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes present basophil activation in vitro, and in 50% of cases a parallel response to release of sulfidoleukotrienes (cellular allergen stimulation test) is observed. These phenomena occur not only in clinically hypersensitive patients, but also in some healthy controls who tolerate NSAIDs. MATERIAL AND METHODS: We studied 16 clinically hypersensitive patients, 22 controls tolerating NSAIDs, and 29 healthy blood donors (clinical NSAID status unknown) using 2 different basophil isolation techniques (buffy coat or plasma leukocytes). RESULTS: In a population of 13 aspirin-tolerant healthy controls and 29 healthy blood donors, basophil activation with aspirin, diclofenac, and naproxen was analyzed at 4 different concentrations. The results in the 2 groups were quite similar in qualitative terms. Choosing a cutoff of 5% and a stimulation index >2, the proportion of positive results increased with the concentration. There were more positive results at all concentrations using the plasma leukocyte technique. CONCLUSIONS: The most important finding of this study is that basophil activation by NSAIDs occurs not only in clinically hypersensitive patients but also, to a very variable extent and on an individual basis, in apparently normal healthy individuals who tolerate NSAIDs. The phenomenon is clearly dose-related, and hypersensitive patients seem to react to lower NSAID concentrations.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Basófilos/efeitos dos fármacos , Hipersensibilidade a Drogas/etiologia , Basófilos/fisiologia , Complemento C5a/fisiologia , Relação Dose-Resposta a Droga , Humanos , Imunoglobulina E/imunologia , SíndromeRESUMO
BACKGROUND: We present the results obtained from the largest series of in vitro diagnostic tests ever reported in patients with clinically validated hypersensitivity to acetylsalicylic acid (ASA)/nonsteroidal anti-inflammatory drugs (NSAID) compared with various categories of controls tolerating ASA/NSAIDs. This multicenter study, which was performed within the framework of the European Network for Drug Allergy (ENDA) group, showed that the basophil activation test (BAT), particularly when used with the 3 NSAIDs aspirin (ASA), diclofenac (DIC), and naproxen (NAP), allows us to confirm the diagnosis of NSAID hypersensitivity syndrome. The results of the cellular allergen stimulation test (CAST) frequently correlate with those of the BAT, although not always. An unexpected finding was that basophil activation by NSAIDs is not an all-or-nothing phenomenon restricted to clinically hypersensitive patients, but that it also occurs in a dose-related manner in some NSAID-tolerant control individuals.Therefore, NSAID hypersensitivity appears as a shift in the normal pharmacological response to NSAIDs. These findings allow us to formulate a new rational hypothesis about the mechanism of NSAID hypersensitivity syndrome, a mechanism that most authors continue to describe as "unknown." METHODS: We enrolled 152 patients with a history of hypersensitivity to NSAIDs and 136 control participants in 11 different centers between spring 2003 and spring 2006. Flowcytometric BAT was performed. RESULTS: The most noteworthy results of our study were that 57% of 140 patients presented very clear-cut positive BAT results to multiple NSAIDs, and 16% were entirely negative. In about 27% of cases, positive results were obtained with 1 or 2 concentrations of a single NSAID. There is clearly a correlation between the results of BAT and CAST. CONCLUSIONS: BAT seems particularly indicated in patients with a clinical history of NSAID intolerance, and in whom a provocation test is not advisable for ethical, clinical, or other reasons. Clear-cut positive results can be considered as confirming a history of NSAID hypersensitivity, although negative results may not exclude it.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/imunologia , Hipersensibilidade a Drogas/imunologia , Adolescente , Adulto , Idoso , Aspirina/efeitos adversos , Aspirina/imunologia , Basófilos/citologia , Basófilos/imunologia , Diclofenaco/efeitos adversos , Diclofenaco/imunologia , Hipersensibilidade a Drogas/diagnóstico , Feminino , Citometria de Fluxo/métodos , Humanos , Leucotrienos/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Naproxeno/efeitos adversos , Naproxeno/imunologia , Curva ROC , Sensibilidade e Especificidade , Adulto JovemRESUMO
Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Bases de Dados Factuais , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Serviços de Informação sobre Medicamentos/organização & administração , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , Humanos , Inquéritos e Questionários , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologiaRESUMO
The application of flowcytometry in the study of basophil activation for the diagnosis of allergic diseases has given interesting results in recent years. The quantification of basophil activation by flowcytometry has been proven to be a useful tool for the assessment of the immediate-type response to allergens mediated by IgE or by other mechanisms in drug allergic patients. Up to now, most basophil activation test studies reported in the literature have used CD69 or CD203c as markers to quantify basophil activation after antigen-specific stimulation. Some technical variations such as the use of whole blood or isolated leukocytes, the addition of IL-3, the conditions of storage of the blood sample, the time of incubation with allergens and their concentration can affect the results of the basophil activation tests. The basophil activation test is more sensitive and specific than other in vitro diagnostic techniques in drug allergy. In various studies, its sensitivity in allergy to muscle relaxant drugs ranges between 36 and 97.7%, with a specificity around 95%. For betalactam antibiotics, basophil activation test sensitivity is 50% and its specificity 90%. For NSAIDs, sensitivity varies between 66% and 75%; specificity is about 93%. Basophil activation test reproduces in vitro hypersensitivity mechanisms involved in immediate-type allergic reactions, allows the diagnosis of allergic and pseudo-allergic reactions particularly for drugs, which are often not detectable by serological techniques, such as determination of specific IgE.
Assuntos
Hipersensibilidade a Drogas/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Citometria de Fluxo/métodos , Animais , Teste de Degranulação de Basófilos/métodos , Basófilos/citologia , Basófilos/imunologia , Hipersensibilidade a Drogas/imunologia , HumanosRESUMO
For the diagnosis of allergy, cellular basophil activation tests (BAT), e.g. histamine or sulfidoleukotriene release tests, have long been introduced, but the expression of basophil activation markers such as CD63 and CD203c detected by flow cytometry has attracted more recent attention. A recent opinion paper in this Journal has stressed not only the potential but also the possible pitfalls of flow-cytometric BAT. We have applied clinical validation of various BAT in various ways for several years, and our experience shows that these new technologies have more potentials and perspectives than pitfalls. A comprehensive review of clinically validated studies on allergy to aeroallergens, insect venoms, latex, food allergens and drugs, e.g. myorelaxants, beta-lactams, pyrazolones and non-steroidal anti-inflammatory drugs, as well as chronic urticaria shows clearly that even with different protocols, reproducible and meaningful results can be obtained. Although the available technologies may still be optimized and better standardized, there are no serious reasons to deprive allergic patients of clinically indicated BAT, which can be performed reliably by any laboratory with allergy and flow-cytometric capacity and expertise.
Assuntos
Teste de Degranulação de Basófilos/métodos , Basófilos/imunologia , Hipersensibilidade/diagnóstico , Citometria de Fluxo , Liberação de Histamina/imunologia , Humanos , Hipersensibilidade/imunologiaRESUMO
Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the skin (urticaria, angioedema) is the second most frequent untoward allergic reaction to drugs. Various aspects of this syndrome, such as its clinical features, the cell types and mediators involved, the role of underlying chronic inflammatory processes, the patterns of cross-reactivity between NSAIDs, the major role of sulfidoleukotrienes (LTC4) and of some other mediators such as prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a long time that there were no reliable in vitro tests for that condition and that diagnostic confirmation can only be ascertained by provocation challenge. This appears no longer to be true, since several recent studies using a leukotriene release test (CAST) or a basophil activation test (BAT) on blood basophils, or a combination of both tests, yields positive results (70-75%) in a sizeable number of clinically validated cases, with a high specificity (above 85%). The finding in that syndrome of hyperreactive basophils suggests that the NSAID hypersensitivity syndrome is due to the associated effect of several factors: 1) Localized inflammatory processes causing a non specific cellular hyperreactivity; 2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction of LTC4 and other mediators by activated mast cells, basophils and eosinophils.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Anti-Inflamatórios não Esteroides/farmacocinética , Aspirina/farmacocinética , Hipersensibilidade a Drogas/metabolismo , HumanosRESUMO
BACKGROUND: After in vitro allergen-specific stimulation, basophils become activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be detected by means of the CAST assay. We assessed the positivity criteria and the reliability of antigen-specific sulfidoleukotriene production (CAST) in the in vitro diagnosis of betalactam (BL) allergic patients. MATERIAL AND METHODS: We studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented with anaphylaxis or urticaria-angioedema within the first 60 minutes after administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or Cefazoline (1/67). All of them had a positive skin test to at least one of the antigenic determinants of Penicillin. As control group 30 adults with negative skin tests who tolerated BL were included. All of them underwent skin tests, oral provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST. RESULTS: Positivity criteria were established by means of ROC curves: a sLT release induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%. Sensitivity of specific IgE is 37.8% and specificity 83.3%. CONCLUSIONS: We have established validated positivity criteria for the CAST technique in patients allergic to Betalactams. This technique is a useful in vitro diagnostic method in patients with IgE-mediated allergy to Betalactam antibiotics.
Assuntos
Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , Lactamas/imunologia , Leucotrienos/análise , Amoxicilina/efeitos adversos , Amoxicilina/imunologia , Anafilaxia/imunologia , Angioedema/imunologia , Antibacterianos/efeitos adversos , Cefazolina/efeitos adversos , Cefazolina/imunologia , Cefuroxima/efeitos adversos , Cefuroxima/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Lactamas/efeitos adversos , Leucotrieno C4/análise , Leucotrieno C4/imunologia , Leucotrieno D4/análise , Leucotrieno D4/imunologia , Leucotrieno E4/análise , Leucotrieno E4/biossíntese , Leucotrienos/imunologia , Masculino , Pessoa de Meia-Idade , Penicilina G/efeitos adversos , Penicilina G/imunologia , Testes Cutâneos , Urticária/imunologiaRESUMO
BACKGROUND: We assessed whether nonsteroidal anti-inflammatory drugs (NSAIDs) may provoke blood basophil activation in vitro in aspirin- and NSAID-hypersensitive patients, as detected by a flowcytometric technique using the CD63 marker--flowcytometric basophil activation test (FAST) assay--in addition to the sulfidoleukotriene (sLT) release--the cellular allergen stimulation test (CAST). METHODS: Sixty aspirin- and/or NSAID-hypersensitive patients were studied. Thirty control patients without history and negative provocation challenge were also included. The percentage of activated basophils after in vitro stimulation with NSAIDs at 3 different concentrations was evaluated by an anti-CD63 phycoerythrin conjugate (FAST assay) and the amount of sLTs released in the cell supernatant by ELISA (CAST assay). RESULTS: For aspirin, the FAST indicated a sensitivity of 41.7%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.4%; for paracetamol 11.7 and 100%, for metamizol 15 and 100%, for diclofenac 43.3 and 93.3%, and for naproxen 54.8 and 74.1%. Many patients showed positive tests to more than 1 NSAID. When considering the first 4 NSAIDs, the global sensitivity increased to 66.7%, while the specificity remained at 93.3%. The addition of the CAST results still increased the sensitivity up to 73.3%, but with a decrease of the specificity to 71.4%. CONCLUSIONS: The FAST shows a high percentage of positive reactions, which may reach 60-70% when 4 NSAIDs are tested and even 88% when the test is performed within 1 month of the last clinical drug exposure and reaction. The test has a high specificity above 90%. The addition of sLT determinations yields additional information in a few isolated cases. It is suggested that this test, when properly used, may help avoid some cumbersome and dangerous provocation challenges.
Assuntos
Anti-Inflamatórios não Esteroides/imunologia , Aspirina/imunologia , Basófilos/imunologia , Hipersensibilidade a Drogas/diagnóstico , Citometria de Fluxo/métodos , Testes Imunológicos/métodos , Leucotrienos/sangue , Adulto , Estudos de Casos e Controles , Hipersensibilidade a Drogas/sangue , Hipersensibilidade a Drogas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Leucotrienos/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs), manifested by cutaneous symptoms and/or airway manifestations represent 20-25% of all hypersensitivity reactions to drugs. Today, it is still claimed that no in vitro diagnostic tests exist for that condition and that the only way to confirm the diagnosis is a provocation challenge. OBJECTIVE: The objective of this study was to assess whether NSAIDs may provoke blood basophil activation in vitro in such patients, as detected by a flowcytometric technique. METHODS: Sixty NSAID hypersensitive patients (38 with cutaneous, 20 with airway and two with cutaneous and airway symptoms) and 30 control patients (15 asthmatics) were selected. Their hypersensitivity was confirmed by documented history indicating at least two clinical episodes to two or more different NSAIDs or by positive oral provocation challenge. Isolated buffy coat leukocytes were stimulated in vitro with aspirin, paracetamol, metamizol, diclofenac, and naproxen. The percentage of activated basophils was evaluated by an anti-CD63. RESULTS: Aspirin showed a sensitivity of 43.3%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.4%. For the other NSAIDs, the sensitivity and specificity values were: for paracetamol 11.7% and 100%, for metamizol 15% and 100%, for diclofenac 43.3% and 93.3% and for naproxen 54.8% and 74.1%. When considering the first four NSAIDs, the global sensitivity raised to 63.3% and specificity to 93.3%. If the number of tests is to be limited for practical reasons, the combination of acetylsalicylic acid and diclofenac at two concentrations yields a sensitivity of 58.3% and a specificity of 93.3%. CONCLUSIONS: Flowcytometric determinations of basophil activation following stimulation with NSAIDs show a high sensitivity (60-70%) with specificity above 90%. So this test may help avoiding some cumbersome and dangerous provocation challenges.
Assuntos
Anti-Inflamatórios não Esteroides/imunologia , Aspirina/imunologia , Basófilos/imunologia , Hipersensibilidade a Drogas/diagnóstico , Citometria de Fluxo/métodos , Acetaminofen/imunologia , Adulto , Idoso , Asma/imunologia , Teste de Degranulação de Basófilos/métodos , Diclofenaco/imunologia , Dipirona/imunologia , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naproxeno/imunologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Urticária/imunologiaRESUMO
Specific diagnosis of immediate type allergies, such as rhinoconjunctivis, asthma, urticaria/angioedema and anaphylaxis, particularly when IgE-mediated, traditionally rests on prick and/or intradermal skin tests and, since about 30 years, on the determination of allergen specific IgEs. Some cellular tests, i.e. tests determining the reactivity of blood cells in vitro, particularly basophils, to allergens, have been available for many years. The determination of histamine release has been widely used in allergy pathophysiological research but its routine application in allergy diagnosis has been restricted to few groups. Basophil degranulation, as determined by microscopic examination, was promoted by some groups in the 1980's but has been largely abandoned since around 10 years ago; an alternative cellular test, based on the determination of sulfidoleukotrienes (LTC4, LTD4, LTE4) produced by IL-3 primed basophils stimulated by allergens in vitro, has been proposed. This test became available commercially in 1993 under the name of CAST (Bühlmann Laboratories, Allschwil, Switzerland). The CAST assay has been used in allergy diagnosis in a variety of indications, such as inhalation allergies, allergies to insect venoms, foods, occupational allergens and various drugs. A large number of reports on CAST diagnostic value, however, have been anecdotal. A meta-analysis of validated and well controlled studies encompasses 37 studies, 1614 patients and 1145 controls. This should definitely establish the value of this diagnostic test, particularly in instances where other in vitro or in vivo diagnostic tests are not reliable, such as food or drug allergies, as well as in non-IgE-mediated immediate hypersensitivity reactions. However, a number of questions about the CAST diagnostic assay are still open or have not been systematically explored. This may explain, in addition to the practical limitations inherent to all allergy cellular tests, why CAST has not yet become a very widely used assay worldwide, having gained broad acceptance in some countries but not in others.
Assuntos
Alérgenos/imunologia , Hipersensibilidade/diagnóstico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade Alimentar/diagnóstico , Humanos , Leucotrienos/biossíntese , Doenças Profissionais/diagnóstico , Testes CutâneosAssuntos
Antígenos CD/análise , Basófilos/imunologia , Hipersensibilidade ao Látex/diagnóstico , Diester Fosfórico Hidrolases/análise , Glicoproteínas da Membrana de Plaquetas/análise , Pirofosfatases/análise , Teste de Degranulação de Basófilos/métodos , Citometria de Fluxo , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tetraspanina 30Assuntos
Antígenos CD/análise , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Citometria de Fluxo , Omeprazol/efeitos adversos , Glicoproteínas da Membrana de Plaquetas/análise , Idoso , Hipersensibilidade a Drogas/imunologia , Citometria de Fluxo/métodos , Humanos , Masculino , Tetraspanina 30RESUMO
BACKGROUND: Immunoglobulin E (IgE)-mediated allergies are postulated to require early allergen contact and sensitization for the full development of sustained IgE levels. METHODS: Thirty-two Beagle dogs from seven litters selectively bred for their high IgE response were sensitized by subcutaneous injection of chicken ovalbumin (OVA), peanut extract and recombinant birch pollen allergen (Bet v 1). In half of the dogs from each litter, sensitization injections were started on the first day of life; the other half of the same litter was first sensitized at the age of 4 months. To evaluate whether early sensitization also predisposes the animals to IgE responses to other allergens later in life, we injected a recombinant timothy grass pollen allergen (Phl p 5) later on, at the age of 10-12 months. Allergen-specific serum IgE and IgG levels were evaluated with enzyme-linked immunosorbent assays. In addition, 21 dogs were challenged with aerosolized OVA to measure bronchoconstrictive changes in lung function. RESULTS: Early sensitized dogs developed significantly higher OVA-specific serum IgE levels than late sensitized dogs, in contrast to the IgG levels, which were lower in these dogs (p < 0.001). The increase in specific serum IgE and IgG following boosting remained different between the two groups for over a year. Titers of specific serum IgE and IgG were also different after sensitization with a new allergen injected later in life for the first time. Dynamic pulmonary compliance and resistance, both parameters for bronchoconstriction induced by OVA aerosol challenge, were also significantly higher in early sensitized dogs (for both parameters, p < 0.01). CONCLUSIONS: Contact with an allergen early in life is decisive for the development of sustained IgE levels and the development of IgE responses to additional allergens encountered later in life. Allergen avoidance during early life may have some preventive effect on IgE-mediated allergy in dogs.
Assuntos
Alérgenos/imunologia , Arachis/imunologia , Imunoglobulina E/imunologia , Ovalbumina/imunologia , Proteínas de Plantas/imunologia , Fatores Etários , Animais , Animais Recém-Nascidos , Antígenos de Plantas , Modelos Animais de Doenças , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/biossíntese , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Testes de Função RespiratóriaRESUMO
BACKGROUND: We assessed the reliability of basophil activation test (FAST) and sulphidoleukotriene production (CAST) in the in vitro diagnosis of allergy to metamizol, evaluating its sensitivity and specificity. METHODS: Twenty-six patients allergic to metamizol and 30 control individuals were studied. Skin tests with metamizol, FAST, and CAST were performed. RESULTS: FAST sensitivity was 42.3% and specificity 100%. The PPV of FAST is 100% and the NPV 99.4%. The likelihood ratio for a positive value cannot be calculated because the specificity is 100% and the likelihood ratio for a negative value is 0.58. CAST sensitivity was 52%, and specificity 90%. The PPV of the test is 5% and the NPV 99.5%. The likelihood ratio for a positive result was 5.2 and that for a negative result 0.53. FAST detects a larger number of cases when patients are studied within the first 6 months after the clinical reaction (chi = 4.2, P = 0.04) than later. Together with skin tests, FAST allowed detection of 69.2% patients allergic to metamizol, the same as CAST 76%. The joint use of the three techniques allowed identification of 76.9% of cases. CONCLUSIONS: FAST and CAST are useful for the diagnosis of allergy to pyrazolones. Its usefulness clearly increases when recent reactions are studied.