Obesity enhances eosinophilic inflammation in a murine model of allergic asthma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Is the prevalence of asthma and related symptoms among Brazilian children related to socioeconomic status?

Objective. To evaluate the relationship between socioeconomic status (SES) and the prevalence of asthma and related symptoms among Brazilian children. Methods. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire was applied to 23,457 six- to seven- year-old schoolchildren (SC) and 58,144 thirteen- to fourteen-year-old adolescents (AD) from 20 Brazilian cities. SES was evaluated by infant mortality index, poverty index, and average nominal income for people older than 10 years of age. Results. Current asthma ranged from 16.5% to 31.2% among SC and from 11.8% to 30.5% among AD and severe asthma from 2.9% to 8.5% (SC) and 2.6% to 9.1% (AD). Higher values were observed in Brazilian-Northern, -Northeastern and -Southeastern centers. No significant association between SES and prevalence of asthma and related symptoms was observed. Conclusions. In Brazil, the prevalence of asthma and related symptoms is quite variable and independent of SES. Copyright © 2008 Informa Healthcare USA, Inc.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 mu g b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmaceutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 mu g b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF).The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV1) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events.In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV1 and asthma control when compared to a combination of budesonide plus formoterol. (Clinical Trial number: ISRCTN60408425). (C) 2013 Elsevier Ltd. All rights reserved.

Prevalence of obesity and relationship wit body mass index and symptoms of asthma in adolescents

To investigate the relationship between Body Mass Index (BMI) and asthma symptoms in adolescents between 13 and 14 years, to estimate the prevalence of obesity in this age group. This is a crosssectional study with a quantitative approach which was rated the Body Mass Index (BMI) and applied the Questionnaire International Study of asthma and Allergies in Childhood (ISAAC) phase III (asthma module) to determine the prevalence of asthma and related symptoms, as well as its severity in 85teenagers. According to the assessment of asthma in relation to BMI, it was found that there were significant findings, as well as in males and females. However, the association between BMI and asthma symptoms, there was a significant association to present as disturbed sleep and impaired speech. Conclusions: In this sample the prevalence of obesity was low, this fact may have contributed to the nonsignificant findings betweenasthma and BMI.

Stem cell factor: a hemopoietic cytokine with important targets in asthma

We review evidence that Stem Cell Factor (SCF) plays an important role in the pathophysiology of asthma. SCF is produced by a wide variety of cells present in asthmatic lung, including mast cells and eosinophils. Its receptor, c-kit, is broadly expressed on mature mast cells and eosinophils. SCF promotes recruitment of mast cell progenitors into tissues, as well as their local maturation and activation. It also promotes eosinophil survival, maturation and functional activation. SCF enhances IgE-dependent release of mediators from mast cells, including histamine, leukotrienes, cytokines (TNF-alpha, IL-5, GM-CSF) and chemokines (RANTES/CCL5, MCP-1/CCL2, TARC/CCL17 e MDC/CCL22); it is required for IL-4 production in mast cells. SCF, acting in concert with IgE, also upregulates the expression and function of CC chemokine receptors in mast cells. Structural and resident airway cells express increased levels of SCF in the bronchus of asthmatic patients. In a murine model of asthma, allergen exposure increased production of SCF by epithelial cells and alveolar macrophages, which was transient and paralleled by histamine release. SCF induced long-lived airway hyperreactivity, which was prevented by local neutralization of SCF, as well as by inhibitors of the production or activity of cysteinyl-leukotrienes. Together, these observations suggest that SCF has an important role in asthma.

Leukotrienes are not essential for the efficacy of a heterologous vaccine against Mycobacterium tuberculosis infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prognostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery

CONTEXTO E OBJETIVO: Associações significativas entre cirurgia do abdome superior e eventos pulmonares do período perioperatório foram investigadas em pacientes com condições pulmonares pré-operatórias submetidos a anestesia geral. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo cujos dados foram retirados de banco de dados obtidos prospectivamente de forma protocolada, de 1 de janeiro de 1999 a 31 de dezembro de 2004, em hospital universitário terciário. MÉTODOS: Estudados 3107 pacientes com mais de 11 anos, American Society of Anesthesiologists (ASA) I, II, III, com cirurgia de abdome superior sob anestesia geral, enviados à sala de recuperação. Condições pré-operatórias analisadas por regressão logística foram: idade, sexo, estado físico ASA, insuficiência cardíaca congestiva, asma, doença pulmonar obstrutiva crônica, insuficiência respiratória e hábito de fumar. Os resultados estudados, ou variáveis dependentes, incluíram eventos intra- e pós-operatórios: broncoespasmo, hipoxemia, hipercapnia, intubação prolongada e secreção de vias aéreas. RESULTADOS: Dos 3.107 pacientes: 1.540 eram homens, 1.649 mulheres, tinham média de 48 anos, 1088 ASA I, 1402 ASA II, 617 ASA III, com insuficiência cardíaca havia 80, asma, 82, doença pulmonar obstrutiva, 122, insuficiência respiratória, 21, hábito de fumar, 428. Pela regressão logística, sexo feminino (p < 0.001), idade maior que 70 anos (p < 0.01), hábito de fumar (p < 0.001) e doença pulmonar obstrutiva crônica (p < 0.02) influenciaram significativamente o desenvolvimento de eventos pulmonares, principalmente hipoxemia e broncospasmo, em ambos os períodos, mas não nos mesmos pacientes. Asma e insuficiência cardíaca não se associaram com eventos pulmonares na sala de recuperação. CONCLUSÃO: em cirurgia do abdome superior sob anestesia geral, sexo feminino, idade maior que 70 anos, hábito de fumar e doença pulmonar obstrutiva crônica foram fatores de risco independentes para a ocorrência de eventos pulmonares intra- e pós-operatórios.

Alterações orofaciais em doenças alérgicas de vias aéreas

OBJETIVO: Apontar as possíveis alterações orofaciais decorrentes do sintoma obstrução nasal em pacientes portadores de doenças alérgicas de vias aéreas superiores, por meio de revisão de literatura. FONTES DE DADOS: Levantamento bibliográfico utilizando bancos de dados eletrônicos, como Medline, Ovid, SciELO e Lilacs, com as palavras-chave asthma, rhinitis e mouth breathing, abrangendo os 30 últimos anos. Foram incluídos artigos de revisão, estudos observacionais e ensaios clínicos. SÍNTESE DOS DADOS: A obstrução nasal é encontrada freqüentemente em doenças alérgicas de vias aéreas, como rinite e asma. A respiração bucal decorrente da obstrução nasal pode interferir de maneira direta no desenvolvimento infantil, com alterações no crescimento do crânio e orofacial, na fala, na alimentação, na postura corporal, na qualidade do sono e no desempenho escolar. CONCLUSÕES: Devido à variedade de alterações orofaciais encontradas na criança respiradora bucal decorrente de obstrução nasal por doenças alérgicas de vias aéreas, é necessário realizar diagnóstico e tratamento precoces por uma equipe multidisciplinar, composta por médico, ortodontista e fonoaudiólogo, contemplando a visão de uma via respiratória única, que traz conseqüências ao crescimento e desenvolvimento do sistema motor oral.

Oxigenoterapia inalatória em pacientes pediátricos internados em hospital universitário

OBJETIVO: Avaliar o uso da oxigenoterapia inalatória em crianças internadas em hospital universitário. MÉTODOS: Estudo prospectivo de crianças atendidas no Pronto-Socorro Pediátrico do Hospital das Clínicas da Faculdade de Medicina de Botucatu e que receberam oxigenoterapia durante a internação, de maio a setembro de 2005. Indicou-se oxigenoterapia se saturação de oxigênio inferior a 90% e frequência respiratória elevada para idade. Crianças em uso crônico de oxigênio ou com necessidade de ventilação mecânica foram excluídas. Foram avaliados: sintomas respiratórios, diagnósticos clínicos, saturação de oxigênio, método e tempo de oxigenoterapia e responsável pela prescrição. RESULTADOS: Foram atendidas 8.709 crianças no pronto-socorro, sendo que 2.769 (32%) apresentaram doenças respiratórias e 97 necessitaram de internação na enfermaria. Destas, 62 (64%) receberam oxigenoterapia. Das 62 crianças, 37 eram do sexo masculino e a idade variou de 2 meses a 14 anos (mediana: 8 meses). A causa de hipóxia foi pneumonia em 52 crianças (84%), asma em cinco, bronquiolite em quatro e traqueomalácia em uma. As prescrições de oxigenoterapia foram feitas por médicos, com monitoração de saturação de oxigênio por oxímetro de pulso. O tempo mediano de administração de O2 foi 6 dias e o cateter nasal foi usado em 94% dos casos, sendo raro o uso de máscaras ou capuz de oxigênio. CONCLUSÕES: A oxigenoterapia inalatória foi mais frequente em crianças com menor idade e em pacientes com pneumonia, sendo sua indicação compatível com critérios internacionais. O uso do cateter nasal mostrou-se seguro, simples, efetivo e de baixo custo.

Leukotriene B(4) is essential for selective eosinophil recruitment following allergen challenge of CD4(+) cells in a model of chronic eosinophilic inflammation

Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class It expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4(+) (but not CD4(-)) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4(+) cells ex vivo. MK886 blocked induction of CCL17 Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalburnin-restimulated CD4(+) cells initiate eosinophil recruitment which is strictly dependent on LTB4 production. (C) 2008 Elsevier B.V. All rights reserved.

The role of chemokines and chemokine receptors in eosinophil activation during inflammatory allergic reactions

Chemokines are important chemotactic cytokines that play a fundamental role in the trafficking of leukocytes to sites of inflammation. They are also potent cell-activating factors, inducing cytokine and histamine release and free radical production, a fact that makes them particularly important in the pathogenesis of allergic inflammation. The action of chemokines is regulated at the level of agonist production and processing as well as at the level of receptor expression and coupling. Therefore, an analysis of the ligands must necessarily consider receptors. Eosinophils are target cells involved in the allergic inflammatory response since they are able to release a wide variety of mediators including CC and CXC chemokines and express their receptors. These mediators could damage the airway epithelial cells and might be important to stimulate other cells inducing an amplification of the allergic response. This review focuses on recently emerging data pertaining to the importance of chemokines and chemokine receptors in promoting eosinophil activation and migration during the allergic inflammatory process. The analysis of the function of eosinophils and their chemokine receptors during allergic inflammation might be a good approach to understanding the determinants of asthma severity and to developing novel therapies.

Relação entre o índice de massa corporal e a gravidade da asma em adultos

OBJETIVO: O aumento do índice de massa corporal (IMC) tem sido associado a uma maior prevalência da asma em adultos. O presente estudo tem o objetivo de avaliar a associação entre a prevalência da obesidade e a gravidade da asma. MÉTODOS: Prontuários de duzentos asmáticos acima dos 20 anos de idade foram avaliados retrospectivamente. A asma foi classificada quanto à gravidade através da história clínica e do diagnóstico registrados, dos resultados da espirometria e da medicação prescrita. O IMC foi calculado e foram considerados obesos os pacientes com IMC > 30 kg/m². RESULTADOS: 23% dos pacientes apresentavam asma intermitente, 25,5%, asma persistente leve, 24%, asma persistente moderada e 27,5%, asma persistente grave. O IMC < 29,9 kg/m² foi observado em 68% dos pacientes e em 32% o IMC foi > 30 kg/m². O odds ratio da relação entre a obesidade e a gravidade da asma foi de 1,17 (CI95%: 0,90-1,53; p > 0,05). CONCLUSÕES: Na amostra estudada não foi encontrada correlação entre a obesidade e a gravidade da asma nem no sexo masculino, nem no feminino.

Cross-reactive IgE antibody responses to tropomyosins from Ascaris lumbricoides and cockroach

Background: Evidence indicates that infection with Ascaris lumbricoides may promote development of allergy and asthma.Objective: To study the role of tropomyosin, a pan-allergen in invertebrates, in IgE responses to A lumbricoides.Methods: Recombinant A lumbricoides and Periplaneta americana tropomyosins were expressed in Pichia pastoris. Levels of IgE to tropomyosins from A lumbricoides and P americana were determined by chimeric ELISA in sera from 119 children living in a parasite-endemic area and 112 patients with cockroach allergy from the allergy clinics. Presence of tropomyosin in A lumbricoides larvae at L3 stage was evaluated by immunofluorescence using mAb IA6, directed against mite tropomyosin. Molecular modeling of P americana and A lumbricoides tropomyosins was performed by using the MODELLER program.Results: A lumbricoides tropomyosin showed 69% to 98% sequence identity to tropomyosins from other invertebrates. The predicted structure of A lumbricoides tropomyosin was similar to that of P americana tropomyosin and showed the characteristic coiled-coil structure. Strong correlation was found for IgE antibodies to tropomyosins from A lumbricoides and P americana in sera from children living in a parasite-endemic area and from patients with cockroach allergy. Larvae of A lumbricoides reacted strongly with mAb IA6.Conclusion: Tropomyosin induces IgE responses in A lumbricoides-infected children and in patients allergic to cockroach.

Mapping the BDA20 Gene to BTAX

The lipocalin family is a large group of proteins that exhibits great structural and functional variation both within and among species, including a significant number of animal-derived aeroallergens, such as the bovine BDA20 (major cow dander allergen). This protein is classified as an occupational allergen causing asthma and other work-related allergic disorders among dairy farmers. Using a somatic cell panel the BDA20 gene was assigned to the bovine X chromosome (BTAX) with a significant concordant value of 97% to the previously mapped reference marker MAF45. A radiation hybrid (RH) mapping approach confirmed the assignment of BDA20 to BTAX. Two-point LOD scores showed that BDA20 is linked to XBM451 with a LOD score of 22.1 for a 0 value of 0.03.

Reduced allergic lung inflammation in rats following formaldehyde exposure: Long-term effects on multiple effector systems

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)