Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses.

Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, RORγt, Foxp3, interleukin (IL)-6, -17, -10, and TGF-ß was assessed by RT-qPCR. IL-6, -17, -10, and TGF-ß levels were determined by ELISA. We observed increased STAT3, RORγt, Foxp3, IL-6, and TGF-ß gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, RORγt, IL-6, and TGF-ß gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.

Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins.

Th17/Treg imbalance contributes to chronic obstructive pulmonary disease (COPD) development and progression. However, intracellular signaling by suppressor of cytokine signaling (SOCS) 1 and SOCS3 and the proteins signal transducer and activator of transcription (STAT) 3 and STAT5 that orchestrate these imbalances are currently poorly understood. Thus, these proteins were investigated in C57BL/6 mice after exposure to cigarette smoke (CS) for 3 and 6 months. The expression of interleukin was measured by ELISA and the density of positive cells in peribronchovascular areas was quantified by immunohistochemistry. We showed that exposure to CS in the 3rd month first induced decreases in the numbers of STAT5+ and pSTAT5+ cells and the expression levels of TGF-ß and IL-10. The increases in the numbers of STAT3+ and pSTAT3+ cells and IL-17 expression occurred later (6th month). These findings corroborate the increases in the number of SOCS1+ cells in both the 3rd and 6th months, with concomitant decreases in SOCS3+ cells at the same time points. Our results demonstrated that beginning with the initiation of COPD development, there was a downregulation of the anti-inflammatory response mediated by SOCS and STAT proteins. These results highlight the importance of intracellular signaling in Th17/Treg imbalance and the identification of possible targets for future therapeutic approaches.

Adults and children with anaphylaxis in the emergency room: why it is not recognized?

PURPOSE OF REVIEW: Despite many international guidelines have been published in the last 10 years, anaphylaxis continues to be underdiagnosed, undernotified, and undertreated. Anaphylactic reactions in adults and children in emergency departments are frequently not recognized, leading to underutilization of epinephrine, and a higher risk of death. RECENT FINDINGS: A few studies have been recently published showing that educational intervention for both physicians and other healthcare professionals improve diagnosis and treatment of anaphylaxis. Moreover, the new International Classification of Diseases, 11th edition improved classification of anaphylaxis, making it easier to be notified. SUMMARY: Anaphylaxis is a life-threatening hypersensitivity reaction that is most frequently seen by emergency physicians and nurses than allergists or immunologists. Education seems to be best strategy to improve management of this severe condition.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions.

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis.

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Drug-induced anaphylaxis: is it an epidemic?

PURPOSE OF REVIEW: The present review addresses the epidemiology, analyzes the current data and promotes global awareness of drug-induced anaphylaxis. RECENT FINDINGS: Anaphylaxis is a medical emergency that may cause death! In the last decade, studies have shown an increasing incidence and prevalence of anaphylaxis. SUMMARY: Drug-induced anaphylaxis fatalities have increased, and this syndrome remains underdiagnosed and undertreated.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Regulatory T-Cell Distribution within Lung Compartments in COPD.

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF+ cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17+ cells only in small airways. A decrease in the density of Treg+, TGF-ß+ and IL-10+ in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF+ cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg+ cell distributions in lung compartments and the decrease in TGF-ß+ and IL-10+ cells in the airways may lead to the obstruction in smokers.

Guia prático sobre controle ambiental para pacientes com rinite alérgica / Practical guide to environmental control for patients with allergic rhinitis

A asma e a rinite alérgica são doenças frequentes e acometem parcela significativa da população, sobretudo crianças. Frequentemente a asma e a rinite coexistem e tem sido documentado que a presença de rinite potencialmente aumenta a gravidade da asma e impacta negativamente na qualidade de vida. Entre os agentes desencadeantes/agravantes dessas doenças são apontados: aeroalérgenos (ácaros do pó domiciliar, fungos, alérgenos de baratas, epitélio de animais, polens e ocupacionais), poluentes intradomiciliares e extradomiciliares (fumaça de tabaco, material particulado liberado pela cocção/aquecimento ­ gás de cozinha, fogão a lenha) e irritantes (odores fortes, arcondicionado). O objetivo desse estudo foi identificar as medidas recomendadas para reduzir a exposição de pacientes sensíveis a esses agentes. Realizou-se busca em base de dados MEDLINE, SciELO e LILACS empregando-se os descritores: environmental control, mite, cockroach, fungi, furry pets, pollen, irritants, smoking, indoor pollution, cooking. Foram revisados os principais estudos e elaborou-se um documento em que são discutidas as relações entre exposição e aparecimento de sintomas, assim como as medidas apontadas como tendo potencial para evitar a exacerbação/ agravamento das doenças alérgicas respiratórias.

Asthma and allergic rhinitis are highly prevalent diseases and they affect a significant share of the population, especially children. Very often, asthma and rhinitis coexist, and the presence of rhinitis has been shown to potentially increase the severity of asthma, with a negative impact on quality of life. Among the triggering or aggravating agents of these conditions it is possible to list: aeroallergens (house dust mites, fungi, cockroach allergens, animal epithelium, pollens and occupational allergens), indoor and outdoor pollutants (tobacco smoke, particulate matter released by cooking/heating ­ cooking gas, wood stoves), and irritants (strong odors, air conditioning). The aim of this study was to identify measures recommended to reduce the exposure of patients sensitive to these agents. A search was conducted on the MEDLINE, SciELO, and LILACS databases, using the following keywords: environmental control, mite, cockroach, fungi, furry pets, pollen, irritants, smoking, indoor pollution, cooking. The main studies were reviewed, and a report was prepared in which the relationships between exposure and the onset of symptoms are discussed, and measures with a potential to prevent exacerbation/ aggravation of allergic respiratory diseases are presented.

Diretrizes brasileiras para o diagnóstico e tratamento do angioedema hereditário ­ 2017 / Brazilian guidelines for the diagnosis and treatment of hereditary angioedema ­ 2017

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises de edema com o envolvimento de múltiplos órgãos. A doença é desconhecida por muitos profissionais da área da saúde e, portanto, subdiagnosticada. Os pacientes que não são diagnosticados e tratados adequadamente têm uma mortalidade estimada de 25% a 40%, devido ao angioedema da laringe, resultando em asfixia. O angioedema de alças intestinais é outra manifestação importante e incapacitante, que pode ser a principal ou a única durante uma crise da doença. Neste cenário, um grupo de especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e do Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) atualizou as diretrizes para o diagnóstico e terapia do angioedema hereditário.

Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40%, due to laryngeal angioedema, which results in asphyxia. Angioedema affecting bowel loops is another important, incapacitating presentation that may be the main or only manifestation during a crisis. In this scenario, a group of experts affiliated with Associação Brasileira de Alergia e Imunologia (ASBAI) and Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) has updated the guidelines for the diagnosis and treatment of hereditary angioedema.

IgE, IgG4 e IgA específicas na alergia ao látex / Specific IgE, IgG4, and IgA in latex allergy

Objetivo: A alergia ao látex é considerada um problema mundial de saúde por estar associada a reações potencialmente fatais. O objetivo principal deste estudo é identificar fatores clínico-laboratoriais associados à sensibilização e alergia ao látex, avaliando as concentrações de IgE, IgG4 e IgA específicas nestas condições. Métodos: Estudo observacional transversal em uma coorte de 400 crianças e adolescentes com defeito do fechamento do tubo neural. Os pacientes realizaram entrevista clínica e foram submetidos a coleta de sangue periférico para a detecção dos níveis séricos de IgE, IgG4 e IgA específicas para látex. As prevalências de sensibilização e alergia ao látex foram calculadas e as variáveis clínico-laboratoriais coletadas foram analisadas. Resultados: A prevalência de sensibilização e de alergia ao látex em pacientes com defeito de fechamento do tubo neural foi de 33,2% e 12,2%, respectivamente. As manifestações clínicas de alergia ao látex mais frequentes foram as cutâneas (79,6%), mas anafilaxia foi observada em 4,75% dos pacientes. Os fatores clínico-cirúrgicos associados à alergia ao látex foram identificados e um escore de sintomas para rastrear os pacientes foi desenvolvido. A concentração de IgE sérica específica para látex ≥ 0,77 kUA/L tem boa acurácia para diferenciar os pacientes sensibilizados assintomáticos dos alérgicos. As dosagens de IgE sérica específica para alérgenos recombinantes também apresentaram boa acurácia no diagnóstico da alergia. Conclusões: Maior concentração de IgE específica para látex e Hevb5, menor concentração de IgG4 específica para látex e escore de sintomas ≥ 40% estiveram associados com alergia ao látex.

Objective: Latex allergy is considered a global health problem because it is associated with life-threatening reactions. The main objective of this study was to identify clinical and laboratory factors associated with sensitization and allergy to latex, assessing the concentrations of latex-specific IgE, IgG4, and IgA. Methods: This was an observational study of a cohort of 400 children and adolescents with neural tube closure defect. Patients underwent a clinical interview and had their blood drawn for the measurement of serum levels of latex-specific IgE, IgG4, and IgA. The prevalence rates of sensitization and allergy to latex were calculated, and clinical and laboratory variables were analyzed. Results: The prevalence rates of sensitization and allergy to latex in patients with neural tube closure defects were 33.2 and 12.2%, respectively. Cutaneous manifestations of latex allergy were the most common ones (79.6%), but anaphylaxis was observed in 4.75% of the patients. Clinical and surgical factors associated with latex allergy were identified, and a symptom scoring system was developed as a screening tool. A latex-specific IgE concentration ≥ 0.77 kUA/L showed good accuracy to differentiate between asymptomatic sensitization and allergy. The measurement of specific IgE to recombinant allergens also showed good accuracy in the diagnosis of allergy. Conclusions: Higher concentrations of latex-specific IgE and Hevb5, lower concentrations of latex-specific IgG4, and a symptom score ≥ 40% were associated with latex allergy.

Anticorpos monoclonais no tratamento da asma / Monoclonal antibodies in asthma treatment

Objetivo: Revisar a aplicação dos principais anticorpos monoclonais já utilizados em estudos clínicos de asma, bem como detalhar os que já estão disponíveis para uso clínico. Fontes de dados: Artigos originais indexados nos bancos de dados MEDLINE e LILACS de janeiro de 1975 a dezembro de 2011, nos idiomas português e inglês, e livros-textos selecionados. Síntese dos dados: Os principais anticorpos monoclonais já estudados no tratamento da asma são os antagonistas de algumas citocinas de perfil TH2 (anti-IL-4, Anti-IL-5, Anti-IL-9 e Anti-IL-13) e da IgE (anti-IgE), embora outros anticorpos, como anti-TNF e anti-CD11a, já tenham sido pesquisados.Conclusões: Embora diversos anticorpos monoclonais já tenham sido utilizados na pesquisa clínica em asma, apenas o omalizumabe (anti-IgE) está disponível comercialmente, porque há evidências demonstrando sua eficácia.

Objective: To review the application of the main monoclonal antibodies which have already been used in clinical studies of asthma,as well as detailing those already available for clinical practice. Sources: Original articles indexed in the databases MEDLINE and LILACS January 1975 to December 2010, Languages: Portuguese and English and selected textbooks. Data synthesis: The main monoclonal antibodies which have already been studied for asthma are cytokines TH2 antagonists (anti-IL-4, Anti-IL-5, Anti-IL-9 e Anti-IL-13) and IgE antagonist (anti-IgE), although otherantibodies, as anti-TNF and anti-CD11a, have already been utilized. Conclusions: Despite the fact that many monoclonal antibodies havebeen utilized in asthma clinical research, only omalizumab (anti-IgE) iscommercially available, because many studies have shown its efficacy.

Beta-2 agonistas de ultra longa duração para o tratamento de asma: há espaço? / Ultra long-term beta-2 agonists for treatment of asthma: is there a place?

Objetivos: Revisar a eficácia e a tolerabilidade dos agentes beta-2 agonistas de longa ação (ultra-BALA) em asmáticos. Métodos: Foi conduzida uma revisão sistemática de estudos clínicos que investigaram a eficácia e tolerabilidade de fármacos beta-2 agonistas administrados 1 vez ao dia, por via inalatória para o tratamento de pacientes com diagnóstico de asma brônquica. A pesquisa incluiu todos os manuscritos publicados na íntegra nos últimos 20 anos, na língua inglesa, utilizando as palavras-chaves ultra-long-acting-beta agonits, carmoterol, indacaterol, vilanterol, arfomoterol, bronchodilators, combination therapy, once-daily AND (asthma treatment [Mesh] OR asthma/drug therapy [Mesh] OR bronchial asthma/therapy [Mesh]) AND randomized controlled trial. Resultados: Foram selecionados 8 ensaios clínicos que avaliaram 975 pacientes asmáticos. O indacaterol foi o agente farmacológico que apresentou estudos publicados em fases mais avançadas em asmáticos. Em estudos pré-clínicos e clínicos o indacaterol mostrou boa eficácia, segurança e tolerabilidade. O início de ação broncodilatadora é rápida e duradoura por 24 horas. Os efeitos adversos mais comuns foram tosse, cefaleia e nasofaringite; geralmente mínimos e de leve intensidade. Conclusões: Os fármacos ultra-BALA podem constituir-se em opções promissoras para uso em dose única diária para um subgrupo de asmáticos que apresenta resposta terapêutica insuficiente e baixa aderência ao tratamento.

Objectives: To review the efficacy and tolerability of the ultra- longactingbeta 2 agonists agents (ultra-LABA) in asthmatics. Methods: We conducted a systematic review of clinical studies that investigated the efficacy and tolerability of inhaled beta-2 agonist drugs administered once daily for the treatment of patients with bronchial asthma. The search included all full-length manuscripts published in the last 20 years, in English, by using the keywords ultra-long-acting beta-agonits, carmoterol, indacaterol, vilanterol, arfomoterol, bronchodilators, combination therapy, once-daily AND (asthmatreatment [Mesh] OR asthma/drug therapy [Mesh] OR bronchial asthma/therapy [Mesh]) AND randomized controlled trial. Results: We selected 8 clinical trials that evaluated 975 patients with asthma. Indacaterol was the pharmacological agent that presented published studies at later stages in asthmatics. In preclinical and clinical studies indacaterol showed good efficacy, safety and tolerability. The bronchodilator effect is fast and lasts for 24 hours. The most common adverse events were cough, headache and nasopharyngitis, often minimal or mild. Conclusions: The ultra-LABA can become promising options for a single daily dose regime for a subgroup of patients presenting insuficiente therapeutic response and low adherence to treatment.

Testes de provocação com drogas: positividade e segurança / Drug Provocation Tests: positivity and safety

O teste de provocação com droga (TPD) é o padrão-ouro para diagnóstico das reações adversas a drogas (RAD). Analisamos resultados de TPD e discutimos os riscos de reações sistêmicas.Método: Estudo retrospectivo e descritivo no qual foram avaliados os prontuários de 500 pacientes com história de RAD no período de janeiro de 2005 a abril de 2009 e selecionados aqueles submetidos a TPD simples cego placebo controlado. Foram realizados TPD com antibióticos (ATB), anti-inflamatórios não esteroidais (AINE), anestésicos locais (A L) e outros. Caracterizamos esta população quanto ao sexo, idade, testes positivos e ocorrência de reações graves. Resultados: Foram realizados 243 TPD em 198 pacientes, 80,8% mulheres e a média de idade de 39,9 anos. Dentre os TPD, realizamos 19 testes com ATB, 26 com AINE seletivos da COX2, 7 com dipirona, 4 com ácido acetil salicílico, 44 com paracetamol, 93 com AL e 17 com outras medicações. Ocorreram 10 TPD positivos (4,1%) e 4 (1,6%) duvidosos. Os testes positivos ocorreram com ATB (2/19), AINE seletivos da COX 2 (2/26), paracetamol (3/44), AL (3/93). Ocorreram 2 reações graves, sendo 1 choque anafilático por cefalexina e 1 anafilaxia sem choque por bupivacaína. Em 4 pacientes (1,6%) houve positividade para o placebo antes da administração da droga ativa.Conclusões: Testes de provocação com drogas são seguros para realização na prática clínica. Os testes devem ser controlados com placebo e supervisionados por um alergista experiente em provocações com drogas.

Drug provocation test (DPT) is considered the gold standard to establish the diagnosis of adverse drug reactions (ADR). We analyzed DPTs results and we discuss severe systemic reactions to them.Methods: A retrospective analysis was conducted on medicai record of 500 patients with ADR history between January of 2005 and April of 2009. Provocation tests, which were single-blind placebo controlled, are reported. There were DPTs with antibiotics, local anesthetics, non¬steroldal antiinflammatory drugs, among other drugs. Patient's features, DPT positivity and its severe adverse reactions were analyzed. Results: The study sample included 243 DPTs in 198 patients (80.8% women) and the mean age was 39.9 years. Ninety-three DPTs were done with local anesthetics, 19 with antibiotics, 44 with acetaminophen, 26 with COX 2 inhibitors, 7 with dipyrone, 4 with aspirin and 17 with other drugs. There were 10 (4.1%) positive and 4 (1,6%) inconclusive tests. The positive tests were due to antibiotics (2/19), COX 2 inhibitors (2/26), acetaminophen (3/44) and local anesthetics (3/93). Two reactions were severe: one anaphylactic shock due to cephalexin and one anaphylaxis without shock due to bupivacaine. Four patients (1,6%) had placebo reaction, before drug administration.Conclusions: Drug provocation tests are safe to be performed in clinicai practice. They should be placebo controlled and done under allergist supervisiono.

Uso a longo prazo de alternativas terapêuticas aos anti-inflamatórios não-esteroidais / Long term use of therapeutic alternatives for non-steroidal anti-inflammatory drugs

A benzidamina e o etoricoxibe são drogas que podem ser utilizadas como alternativa terapêutica em pacientes com hipersensibilidade aos anti-inflamatórios não-esteroidais (AINEs). O objetivo do estudo foi avaliar a utilização destas medicações a longo prazo em pacientes com teste de provocação negativo. Métodos: Pacientes com hipersensibilidade aos AINEs que apresentaram teste de provocação negativo foram contactados por telefone e questionados sobre a utilização posterior da drogatestada. Os pacientes que responderam que não voltaram a utilizar a droga foram questionados sobre os motivos pelo qualnão usaram. Resultados: Dos 53 pacientes testados, 50 apresentaram teste de provocação negativo. Destes, 36 foram contactados por telefone e 18 haviam utilizado novamente a droga sem qualquer reação. Dentre os que não foram expostos novamente aos medicamentos, metade não o fez porque não julgou necessário, e a outra metade por receio de uma nova reação. Conclusões: O teste de provocação oral é seguro para a determinação de alternativas terapêuticas, mas a eficácia do mesmo está diretamente relacionada ao entendimento do paciente quanto a possibilidade de novas reações. Além disso, as indicações para o teste também devem ser revistas.

Benzydamine and etoricoxib are drugs that can be used as an alternative therapy in patients with hypersensitivity to thenon-steroidal anti-inflammatory drugs (NSAIDs). The aim of the study was to evaluate the long-term use of these drugs inpatients with a negative drug provocation test. Methods: Patients with NSAIDs hypersensitivity that presented a negative drug provocation test were contacted by telephone and questioned about the subsequent use of the tested drug. The patients who answered that they had not used the drug again were questioned on the reasons for not using it. Results: Of the 53 patients tested, 50 presented a negative drug provocation test. Of these, 36 were contacted by telephone and 18 had used the drug again without any reaction. Among the ones that were not exposed again to the drugs, halfof them had not used because they didn't judge necessary, andt he other half were afraid of a new reaction. Conclusions: The drug provocation test is safe for the determination of an alternative therapy, but the effectiveness oft he test is directly related to the patient's understanding about the possibility of new reactions. Besides, the indications for the test should also be reviewed.

Papel da imunoglobina intravenosa na asma brônquica / Role of intravenous immunoglobulin in bronchial asthma

Há mais de 20 anos a imunoglobulina humana exógena vem sendo aplicada, principalmente por via intravenosa (IgIV), em diferentes doenças e com diferentes funções, na prática clínica. Classicamente era usada apenas em iunodeficiências primárias, mas outros benefícios dessa medicação foram documentados em outras doenças imuno-inflamatórias, tais como, doença de Kawasaki e púrpura trombocitopênica idiopática. Alguns autores passaram então a aplicar IgIV em pacientes com asma de difícil controle, corticosteróide dependente, e obtiveram resultados interessantes, no entanto, trabalhos duplo-cegos, randomizados e controlados falharam em mostrar o benefício dessa medicação na asma grave. Descrevemos neste artigo alguns aspectos sobre as indicações de IgIV e aspectos importantes na abordagem da asma de difícil controle. Revisamos os principais trabalhos publicados sobre a aplicação de IgIV na asma brônquica, incluindo fatores imunopatológicos implicados e possíveis mecanismos de ação da medicação na doença.

Immunoglobulin has been used in medicine for more than twenty years. Initially, it was administered mainly to primary immunodeficiencies patients, but late r was also demonstrated benefits in inflammatory diseases, like Kawasaki Disease and thrombocytopenic purpura. Some physicians started to use it in difficult to contrai asthma with interesting results. However, there is not large, randomized, placebo-controlled and doubleblind studies supporting the efficacy of intravenous gammaglobulin in asthma. This study reviews the literature and discusses intravenous gammaglobulin indications in the treatment of difficult to contrai asthma and its possible mechanisms of action.