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.

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.

Difficult-to-control asthma management through the use of a specific protocol

The present study is a critical review of difficult-to-control asthma, highlighting the characteristics and severity of the disease. It also presents a protocol for the management of patients with this asthma phenotype. The protocol, which was based on relevant studies in the literature, is described and analyzed.

Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis

OBJECTIVES: Severe asthma is found in approximately 10 percent of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD), nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis. RESULTS: We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4 percent); 18 (7.3 percent) had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3 percent) had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6 percent) patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6 percent) patients. Vocal cord dysfunction was suspected in 16 (6.5 percent) and confirmed through laryngoscopy in 4 (1.6 percent). The patient records provided CT scans of the chest for 105 patients, and 26 (24.8 percent) showed bronchiectasis. DISCUSSION: Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.