CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Mepolizumabe na doença respiratória exacerbada por aspirina - DREA / Mepolizumab in aspirin-exacerbated respiratory disease - AERD

Relato de caso que ilustra a eficácia e a segurança do uso do mepolizumabe na doença respiratória exacerbada por aspirina (DREA). A utilização de anticorpo monoclonal no tratamento desta doença respiratória de difícil tratamento tem possibilitado o controle da inflamação crônica e o maior conhecimento sobre a fisiopatogenia da doença.

This case report shows the efficacy and safety of mepolizumab in aspirin-exacerbated respiratory disease (AERD). The use of monoclonal antibodies in the treatment of this severe disease has provided improved control of chronic inflammation and greater understanding about the pathophysiology of the disease.

Avaliação do fenótipo atópico nos pacientes com DREA / Evaluation of atopic phenotype in patients with DREA

Introdução: A doença respiratória exacerbada por anti-inflamatórios (DREA) é uma síndrome bem caracterizada, composta por asma, polipose nasal e intolerância a aspirina e anti-inflamatórios não esteroidais (AINEs). Apesar de já bem definida, há uma heterogeneidade entre a população de pacientes com diagnóstico de DREA. O objetivo desse trabalho foi avaliar o fenótipo atópico nos pacientes com DREA. Métodos: Foi realizado um estudo retrospectivo com pacientes com DREA acompanhados em um serviço terciário. Esses pacientes foram classificados em dois grupos: atópicos e não atópicos. Foram avaliados também dados como gravidade da asma, AINEs envolvidos na reação, e IgE sérica total. Resultados: Foram analisados 70 pacientes, destes 55 (78,6%) eram mulheres. A média de idade era de 54 anos. Do total de pacientes, 32 (45,7%) eram atópicos. Os pacientes atópicos apresentavam média de início de asma mais precoce (22 anos) e maior tempo de doença (31 anos) do que os não atópicos. A média de IgE sérica total era maior nos atópicos (742,1 UI/mL). No grupo dos pacientes com DREA e atopia, a pesquisa de IgE sérica específica mostrou-se positiva para os ácaros em 90,6% dos pacientes. A maioria dos pacientes atópicos (71%) relatava reação a múltiplos AINEs. Os principais medicamentos relacionados às exacerbações respiratórias nos pacientes com DREA foram: AAS em 72,1% dos casos; dipirona em 61,8%; diclofenaco em 45,6%; e cetoprofeno e ibuprofeno em 27,9% dos casos cada um. Conclusões: Existem diferenças entre os pacientes com DREA conforme a presença ou não de atopia. Os atópicos apresentam início de sintomas mais precoce, maior tempo de duração de asma, necessitam de mais medicação para controle e apresentam hipersensibilidade a um número maior de AINEs, sendo que o principal medicamento causador de sintomas também varia entre os dois grupos.

Introduction: Aspirin-exacerbated respiratory disease (AERD) is a well characterized syndrome in which asthma, nasal polyposis, and intolerance to aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) coexist. Even though it is well defined, the population of patients diagnosed with AERD is very heterogeneous. The aim of this study was to evaluate atopic phenotype in patients with AERD. Methods: A retrospective study was performed with patients with AERD followed at a tertiary hospital. These patients were classified into two groups: atopic and non-atopic. Clinical characteristics and data such as asthma severity, NSAIDs involved in the reaction and total serum IgE were also evaluated. Results: Seventy patients were analyzed, of which 55 (78.6%) were women. Mean age was 54 years. Of the total sample, 32 (45.7%) were atopic. Atopic patients had a lower mean age at the onset of asthma (22 years) and presented a longer mean disease duration (31 years) than non-atopic patients. Mean total serum IgE was higher in atopic patients (742.1 IU/ mL). In the group with AERD and atopy, the specific serum IgE test was positive for mites in 90.6% of the patients. Most atopic patients (71%) reported reaction to multiple NSAIDs. The main drugs related to respiratory exacerbations in patients with AERD were: aspirin in 72.1% of cases; dipyrone in 61.8%; diclofenac in 45.6%; ketoprofen and ibuprofen in 27.9% each. Conclusions: There are differences between patients with AERD according to the presence or absence of atopy. Atopic patients have an earlier onset of symptoms and a longer duration of asthma, they require more medication to control the condition and are hypersensitive to a greater number of NSAIDs; the drug that most commonly triggered symptoms also differed between the two groups.

Reações adversas aos antiinflamatórios não esteroidais / Adverse reactions to nonsteroidal anti-inflammatory

Objetivo: rever as principais reações adversas aos antiinflamatórios não esteroidais (AINEs) publicadas nos últimos dez anos. Fontes dos dados: artigos originais indexados nos bancos de dados Medline e LILACS de janeiro de 1998 a dezembro de 2007, e livros textos selecionados. Síntese dos dados: esta revisão enfocou: classificação, mecanismos. de ação, principais manifestações clínicas, tratamento e dessensibilização à aspirina.Conclusões: os AINEs são drogas amplamente usadas, por outro lado apresentam alta prevalência entre as reações adversas a drogas, as quais veem aumentando nos últimos anos. História clínica bem elaborada é a chave do diagnóstico. O diagnóstico pode ser estabelecido pela prova de provocação com ácido acetilsalicílico. As reações adversas aos AINEs podem ser fatais. As reações adversas devem ser notificadas para que se estabeleça o perfil de segurança desses medicamentos.

Objective: to review the main adverse reactions to nons 8 years. Data base: original papers indexed on Medline and LILACS data bases from january of 1998 to december of 2007 and select books. Data synthesis: this review focuses on: classification, action mechanisms, clinical manifestations, treatment and aspirin desensitization. Conclusion: NSAIO are widely used nevertheless they have a high prevalence of drug reactions which is increasing in recent last years. A good clinical history is the key to diagnosis. The gold standard to diagnosis is the aspirin challenge. Adver se reactions to NSAIO may be fatal. The adverse reactions to drugs should be notified to establish the drug safety profile.

Genetic Markers for Differentiating Aspirin-Hypersensitivity

Aspirin-induced asthma (AIA) and aspirin-induced urticaria/ angioedema (AIU) are two major aspirin-related allergies. We summarize recent findings related to their molecular genetic mechanisms in order to identify genetic susceptibility markers for differentiating AIU and AIA. The overproduction of cysteinyl leukotriene has been suggested as a mechanism in both AIU and AIA. Increased expression of CYSLTR1 with CYLSTR1 and CYSLTR2 polymorphisms are new findings in AIA, while the ALOX5 promoter polymorphism has been noted in AIU. An HLA study suggested that DPB1*0301 is a strong genetic marker for AIA, and that HLA DRB1*1302 and DQB1*0609 are markers for AIU susceptibility. Several single nucleotide polymorphisms (SNPs) in the promoters of EP2, TBX21, COX-2, Fc(epsilon)RI(beta), and TBXA2R were associated with AIA, while an Fc(epsilon)RI(alpha) promoter polymorphism was associated with AIU. The functional studies of the key genes involved in AIA and AIU are summarized. The identification and functional study of genetic markers for AIA and AIU susceptibility would further elucidate the pathogenic mechanisms and facilitate the development of early diagnostic markers to establish therapeutic targets.

Prevalence of aspirin sensitivity among asthmatic patients with mild to moderate severity and its clinical characteristics / 천식및알레르기

BACKGROUND: While aspirin sensitivity has been known to be common among patients with severe asthma, its frequency among asthmatics with mild to moderate severity remains to be learned. OBJECTIVES: To elucidate the frequency of aspirin sensitivity and its clinical characteristics among asthma patients with mild to moderate severity. MATERIAL AND METHODS: A total of 96 asthmatics with mild to moderate severity were enrolled. They underwent lysine-aspirin and methacholine bronchial provocation tests, and gave their induced sputum after the lysine-aspirin challenge. RESULTS: FEV1 declined greater than 20% compared with baseline FEV1 in 11 of 96 patients on the lysine-aspirin challenge. The frequency of aspirin sensitivity was higher among patients with enhanced bronchial hyperresponsiveness to methacholine (PC20 < 1 mg/ml) than among those without it (27.3% vs. 6.8%). The frequency was also higher in those with induced sputum eosinophil count higher than 3% than among those without it (38.9% vs. 0%). However, it was not associated with other risk factors such as age, sex, atopy, nasal polyps, and rhinosinusitis. CONCLUSION: More than 10% of mild to moderate asthmatics have aspirin sensitivity even though they have experienced no history of aspirin sensitivity which may be related with bronchial hyperresponsiveness to methacholine and eosinophil activation.

Leukotriene C4 synthase promoter polymorphism in aspirin - induced asthma / 천식및알레르기

BACKGROUND: Aspirin/NSAIDs can release cysteinyl-leukotriene (cys-LTs) into airways and precipitate asthmatic symptoms in aspirin - induced asthma(AIA). It has been reported that there is profound overexpression of LTC4 synthase in their bronchial mucosa, compared to aspirin-tolerant asthma. Objective : We observed whether genetic polymorphism of LTC4 synthase may be predisposed to LTC4 synthase overexpression in AIA. Subject and METHOD: Forty - four AIA patients having positive responses on lysin aspirin bron choprovocation tests and 47 non - aspirin induced asthma ( non - AIA ) patients having negative challenges and 32 healthy controls were enrolled. The genotypes of the promoter LTC4 synthase gene ( A,C transversion ) were determined by polymerase chain reaction and restriction fragment length polymorphism ( RFLP ) method. RESULTS: LTC4 synthase promoter polymorphism ( A444C btransversion) was not significantly different between non - AIA and AIA patients (p>0.05). Conclusion These findings suggest that genetic polymorphism of LTC4 synthase promoter may not be predisposed to LTC, synthase overexpression in AIA.